Long-Term Memory Plasticity: A Decade-Long Connectivity Study Post Anterior Temporal Lobe Resection

Long-Term Memory Plasticity: A Decade-Long Connectivity Study Post Anterior Temporal Lobe Resection | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Long-Term Memory Plasticity: A Decade-Long Connectivity Study Post Anterior Temporal Lobe Resection Marine Fleury, Lawrence Binding, Peter Taylor, Fenglai Xiao, Davide Giampiccolo, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3936758/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 15 Jan, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Approximately 40% of individuals undergoing anterior temporal lobe resection for temporal lobe epilepsy experience episodic memory decline. Despite the importance of early memory network changes, long-term plasticity and its impact on memory function are unclear. Our study investigates neural mechanisms of memory recovery and network plasticity over nearly a decade post-surgery. From 3–12 months to 10 years postoperatively, we assessed memory network changes in 25 patients (12 left-sided resections) relative to 10 healthy matched controls, using longitudinal, task-based functional MRI and standard neuropsychology assessments. In a predominantly seizure-free cohort, our findings highlight the potential for sustained cognitive improvement and reduced medication needs over a decade after epilepsy surgery. We observed specific changes in memory networks and identified regions crucial for long-term verbal and visual memory recovery. These findings endorse strategic approaches in epilepsy treatment: advocating for conservative surgeries and promoting the long-term use of cognitive rehabilitation for ongoing recovery. Biological sciences/Neuroscience/Diseases of the nervous system/Epilepsy Biological sciences/Neuroscience/Cognitive neuroscience neuroplasticity episodic memory functional connectivity anterior temporal lobe resection fMRI Figures Figure 1 Figure 2 Figure 3 Introduction Anterior temporal lobe resection (ATLR) is the most commonly performed surgical treatment for medically intractable temporal lobe epilepsy (TLE). 1 This involves the partial removal of temporal neocortical and mesial temporal structures including the anterior hippocampus, parahippocampal and fusiform gyri; structures critical for successful memory formation. 2,3 Concordantly, noteworthy episodic memory deficit affects up to 40% of people with epilepsy (PWE) postoperatively. 1,4 Identifying regions crucial for effective memory reorganization that may be spared during epilepsy surgery may help mitigate against memory loss caused by surgical intervention. Additionally, understanding post-operative plasticity could assist the development of strategies to promote long-term memory recovery. Longitudinal functional MRI (fMRI) studies have highlighted plasticity of episodic memory function up to 2 years following ATLR. 5,6 Existing task-based fMRI research primarily compared mid-term (up to 2 years) postoperative memory activations with preoperative or short-term (3 months) post-surgical activations. 5–8 These showed that increased engagement of contralateral hippocampus and neocortex, including the insula and orbitofrontal cortex (OFC), was supportive of postoperative memory function in PWE. 5,7,9 Network-level analyses however have only been performed on resting-state fMRI. 10,11 Task-based fMRI connectomics is needed to comprehensively model postoperative changes in the functional architecture of episodic memory and its association with memory function following ATLR. This comes in light of recent evidence of distributed functional 5,8,12 and structural alterations 13,14 before and after ATLR, together with widespread postoperative deficits across verbal and non-verbal memory domains, regardless of surgical laterality. 15 Network studies using psychophysiological interaction (PPI) 16 analysis model the changes in functional couplings between a seed and whole-brain regions specific to task performance. Using PPI, we previously showed widespread functional connectivity increases in TLE between bilateral medial temporal lobes (MTLs) and to contralesional temporal and extra-temporal regions that supported better memory. 12 Investigating longitudinal connectivity changes specific to the memory connectome would inform on the network’s potential for adaptive plasticity beyond the two-year postoperative mark. A critical research question emerges; whether memory functional plasticity after surgery represents a short-term response to surgical insult, or is an ongoing, dynamic process that evolves over time. If plasticity is indeed an ongoing phenomenon, identifying patterns of memory-node abnormalities in longitudinal studies may shed light on the biology of rehabilitation and aid stratifying patients for optimal cognitive support strategies. Additionally, comprehending the long-term memory outcome and its supporting network is vital for effective pre-operative counselling of PWE and their families. This study aimed to identify neural mechanisms underlying verbal and visual memory network plasticity and recovery long-term after epilepsy surgery. In a longitudinal design, we ( 1 ) assessed changes in task-associated functional connectivity from 3–12 months to 10 years after ATLR using generalized PPI, and ( 2 ) correlated memory network alterations with improvement in episodic memory function. We hypothesized that there will be continued long-term plasticity of episodic memory networks 5,17 , particularly adaptive in people who are rendered seizure-free post-operatively 15 . Given our previous research and short-term plasticity effects, changes in local MTL connectivity including connections to the fusiform gyrus are of a priori interest 5,9,17 . Results The study cohort was followed-up 3 months, 12 months, and 10 years after ATLR (and similar in controls). 'Short-term' and 'long-term' respectively denote a combined 3–12-month (median = 11, interquartile range (IQR) = 8–12) timepoint and a 10-year (median = 9, IQR = 8–10) follow-up. Subjects Patient demographics and clinical features at 3–12 months and 10 years are outlined Table 1. Long-term postoperatively, seizure-freedom (i.e., ILAE outcome 1) was observed in 83% of left and 92% of right ATLR. Kruskal-Wallis and two-sided Fisher exact tests respectively showed non-significant differences in age and sex between patient and control groups (Table 1). There was no significant difference between both patient groups in clinical features (using Kruskal-Wallis tests). Postoperative neuropsychology Long-term memory change Longitudinal changes in memory were determined as clinically significant based on a reliable change index (RCI), using 95% confidence interval. Healthy controls From 3–12 months to 10 years, healthy controls’ memory was as follows: for verbal memory, 12.5% improved, 12.5% no change, while 75% declined; for visual memory, 12.5% improved, 50% no change, while 37.5% declined. At the group-level, there was a clinically significant improvement in verbal memory from preoperative to 3–12 months timepoints, which was reversed from 3–12 months to 10 years (i.e., significant decline). For visual memory, group-level performance remained stable over time. Left ATLR In left ATLR, clinically significant changes in postoperative memory from 3–12-month to 10-year assessments were as follows: for verbal memory, 50% improved, 17% showed no change, while 33% declined; for visual memory, 42% improved, 8% remained stable, while 50% declined. At the group-level, verbal memory performance was stable from preoperative to 3–12-month follow-ups, while there was a clinically significant improvement from 3–12-months to 10 years. At the 10-year follow-up compared to preoperatively, 75% of left ATLR patients demonstrated positive outcomes in verbal memory, with 33% returning to baseline performance and 42% showing improved memory. Visual memory significantly improved from preoperative to 3–12-month assessments and remained stable to the longer term (Fig. 1). Right ATLR Clinically significant changes in right ATLR were as follows: for verbal memory, 31% improved, 46% no change, while 23% declined; for visual memory, 38% improved, 15% no change, while 38% declined. At the group-level from preoperative to 3–12-month assessments, there was an initial visual memory decline that resolved in the longer-term: group-average increased from 3–12 months to 10 years despite not reaching significance (Fig. 1 and Table 2). Ten years postoperatively relative to preoperatively, 58% of right ATLR patients showed positive outcomes in visual memory, with 33% returning to baseline performance and 25% exhibiting better memory. For verbal memory, group-level performance remained stable over time. Group difference in memory outcome One-way ANOVAs were used on parametric z-scores and post-hoc tests were corrected using Tukey's Honestly Significant Difference (HSD) adjustment. Group averages in memory z-scores and statistics are shown Table 2 ( supplementary material details preoperative neuropsychology and confidence intervals). Three–12 months Short-term postoperatively, healthy individuals’ verbal memory was significantly better than that of left ATLR ( P < 0.001) and right ATLR ( P = 0.004). For visual memory, controls performed significantly better than right ATLR ( P = 0.002) but not left ATLR ( P = 0.25). Ten years : Long-term postoperatively, controls’ verbal memory was significantly greater than in left ATLR ( P = 0.028) but not right ATLR ( P = 0.076). There was no significant difference in long-term visual memory between control and patient groups (left ATLR vs . controls: P = 0.36; right ATLR vs . controls: P = 0.061). Across postoperative timepoints, there was no significant difference in verbal or visual memory z-scores between ATLR groups (see supplementary material ). Changes in functional connectivity 3–12 months to 10 years post-surgery relative to changes in controls Table 3 shows detailed results from the flexible factorial design analysis. Left ATLR relative to controls Words remembered From 3–12 months to 10 years after left ATLR, there was increased connectivity between both MTL seeds and contralesional posterior parahippocampal gyrus, and between remnant left MTL and remnant posterior fusiform gyrus. Extra-temporally, connectivity was longitudinally increased between the remnant MTL and right anterior cingulate cortex, but significantly decreased between the contralesional hippocampal seed and right thalamus. Faces remembered Long-term compared to short-term after left ATLR, there was enhanced functional connectivity between the remnant left MTL and remnant parahippocampal and bilateral posterior fusiform gyri, and between the contralesional hippocampal seed and right amygdala. Neocortically, there was increased connectivity between the remnant MTL and left inferior temporal gyrus, and between the contralesional hippocampal seed and right superior frontal gyrus from 3–12 months to 10 years. Right ATLR relative to controls Words remembered Functional connectivity long-term compared to short-term after right ATLR was increased ipsilesionally, between remnant right MTL seed and remnant fusiform gyrus. There was no significant MTL-to-neocortex change in functional connectivity. Faces remembered Functional connectivity from 3–12 months to 10 years after right ATLR was enhanced between the contralesional hippocampal seed and bilateral posterior fusiform gyri, and between the remnant right MTL seed and right posterior parahippocampal gyrus. Extra-temporally, the contralesional hippocampal seed showed stronger functional couplings with right lingual gyrus, and reduced connectivity with the left insula, long-term relative to short-term post-surgery. Correlation between longitudinal changes in connectivity and memory recovery 3–12 months to 10 years postoperatively Generalized PPI analyses inherently modelled memory-encoding networks underlying successful memory formation. Therefore, all reported activations represent connectivity that is supportive of memory function. To look at neural substrates of more efficient memory recovery, correlations were performed, revealing the most adaptive longitudinal connectivity changes. Longitudinal changes in task-based connectivity significantly correlated with improvement in memory z-scores from 3–12 months to 10 years are presented in Fig. 2 and Table 4 for verbal memory, and Fig. 3 and Table 5 for visual memory in both resection groups. Left ATLR relative to controls Words remembered From 3–12 months to 10 years after left ATLR, improvement in verbal memory was significantly correlated with increased functional connectivity between both MTL seeds and the right posterior parahippocampal gyrus, and between the remnant left MTL seed and remnant posterior fusiform gyrus. At the extra-MTL level, verbal memory improvement was significantly associated with reduced long-term connectivity between remnant left MTL and left parietal gyrus, and between the contralesional hippocampal seed and right supramarginal gyrus and thalamus, 10 years relative to 3–12 months post-surgery. Faces remembered Short relative to long-term after left ATLR, longitudinal increases in connectivity between the remnant left MTL seed and bilateral posterior fusiform gyri and between the contralesional hippocampal seed and remnant hippocampus significantly supported visual memory improvement. Neocortically, visual memory improvement was significantly correlated with longitudinal enhancement of bilateral fronto-temporal connectivity; between remnant MTL and left OFC, left insula and bilateral temporal cortex, and between contralesional hippocampal seed and left middle temporal gyrus, right OFC, and right superior frontal gyrus. Right ATLR relative to controls Words remembered Similar to left ATLR, from 3–12 months to 10 years after right ATLR verbal memory improvement was significantly correlated with increased connectivity between remnant right MTL seed and remnant posterior fusiform gyri, and between the contralesional left hippocampal seed and remnant parahippocampal gyrus. At the extra-MTL level, long-term verbal memory improvement was significantly supported by reduced connectivity between contralesional left hippocampus and left temporal cortex, and between the remnant MTL and right supramarginal gyrus and right thalamus. Faces remembered From short to long-term after right ATLR, longitudinal increases in functional connectivity between the remnant right MTL and contralesional posterior fusiform, and between contralesional hippocampal seed and bilateral fusiform gyri were supportive of long-term visual memory improvement. At the extra-MTL level, improvement in visual memory significantly correlated with increased functional connections between the contralesional hippocampal seed and right lingual and middle temporal gyri, and between the remnant MTL and contralesional inferior temporal gyrus, 10 years compared to 3–12 months after right ATLR. Discussion This longitudinal study explored neural processes underlying memory network recovery long-term after anterior temporal lobe resection. Patient-specific connectivity changes of the episodic memory-encoding network were ( 1 ) assessed from 3–12 months to 10 years postoperatively relative to changes in healthy controls, and ( 2 ) correlated with improvement in long-term verbal and visual memory function. Our findings revealed key increases in functional connections over the long term, to posterior MTL regions including the right posterior parahippocampal gyrus and remnant /bilateral posterior fusiform gyri. These changes were central to verbal and visual memory recovery from 3–12 months to 10 years after ATLR. Reduced thalamo-MTL connectivity and stronger connections to the bilateral orbitofrontal cortex (OFC) and left insula, 10 years relative to 3–12 months postoperatively, supported improvement in late verbal and visual memory, respectively. Long-term postoperative memory changes In intractable TLE, recurrent seizures and increasing drug load negatively impact mood, cognition, and integrity of memory-related brain regions. 18,19 In this study, most postsurgical PWE achieved seizure freedom, and approximately half reduced or ceased ASMs across follow-ups (50% left, 54% right ATLR). From before to 3–12-months post-ATLR, healthy controls exhibited a verbal memory learning/test-retest effect that was absent in postsurgical PWE, suggesting an immediate surgical insult on cognitive function. 15,20 Beyond 3–12 months, our predominantly seizure-free cohort demonstrated cognitive stability at the group-level, consistent with neuropsychological research, reviewed here. 21 Patient-specific recovery is however evident over the long term. From 3–12-months to 10 years, 50% of left ATLR and 38% of right ATLR showed clinically significant improvement in verbal and visual memory, respectively. Visual memory improved in people who had left-sided resection, with group-level performance significantly increasing above baseline within the first year post-surgery and stabilizing over the longer term. Ten years postoperatively, 75% of left ATLR and 58% of right ATLR had good verbal and visual memory outcomes compared to preoperatively, with improved performance or return to baseline. Enhancement of baseline performance possibly translates to successful nociferous cortex removal and corresponding release of functions and reserve capacities previously suppressed by ongoing seizures 22,23 . This has important clinical implications for presurgical discussion and cognitive rehabilitation endorsement. 24 Our findings demonstrate that ATLR facilitates long-term medication reduction, sustained seizure freedom, and related cognitive stabilization or improvement long-term post-operation. 15 Medial temporal plasticity over a decade postoperatively Neuroimaging evidence demonstrates the role of posterior MTL regions in subsequent verbal memory formation, with heightened engagement in TLE. 3,12,25 Our findings showed that from 3–12 months to 10 years postoperatively, long-term reorganization toward posterior fusiform and right posterior parahippocampal gyri was significantly supportive of postoperative improvement in visual and verbal memory. Among left and right ATLR patients, those with stronger verbal memory improvement across follow-ups exhibited stronger increases in connectivity between left MTL and right posterior parahippocampal gyrus, alongside ipsilesional fusiform connectivity (remnant seed–remnant fusiform). Similarly, long-term visual memory improvement from 3–12 months to 10 years was significantly correlated with extensive increases in left MTL–bilateral fusiform connectivity. Activation-based fMRI studies have denoted postoperative plasticity effects to the contralesional hippocampus within one year post-ATLR. 5,7 Using network analyses, we reveal that longer-term plasticity involves a more bilaterally connected medial temporal network invariant of surgical laterality, thereby challenging traditional concepts of domain-specific functional lateralization. Long-term after ATLR, the importance of successful network reorganization toward structures that putatively underly the processing and specialized pattern recognition of graphic and contextual stimuli is emphasized. 25,26 Enhancing their integration with the broader brain network through preoperative pre-habilitation and postoperative rehabilitation presents a promising clinical avenue to facilitate long-term cognitive recovery. Reduced thalamic recruitment and verbal memory recovery Reduced thalamic recruitment is associated with verbal memory improvement from 3–12 months to 10 years after ATLR. Specifically, longitudinal decreases in functional couplings between left MTL–left parietal/temporal cortex and right MTL–right supramarginal gyrus, along with ongoing reduction in right MTL-right thalamic connectivity correlated significantly with long-term verbal memory recovery, irrespective of lesion side. The thalamus plays a crucial role in ictogenesis 27 and seizure propagation. 28 The nociferous cortex hypothesis suggests that chronic epilepsy disrupts extra-temporal regions through abnormal epileptiform activity propagation, 22 and successful removal of epileptogenic cortex, leading to seizure-freedom, is associated with cognitive improvement. 10,15 The thalamus correspondingly modulates task performance, with a reduced task-related engagement in healthy controls that is maladaptively heightened in active generalized epilepsy. 28,29 Longitudinal decreases in MTL-seeded thalamic and extra-temporal connectivity may serve as an imaging biomarker of memory network convalescence, coinciding with nociferous cortex removal and seizure cessation. Future studies should explore whether reduced thalamic and extra-temporal connectivity corresponds to expected gains in executive function. Frontal plasticity and visual memory recovery From 3–12 months to 10 years postoperatively, heightened extra-MTL engagement offers computational support during successful visual encoding. This was especially evident through the longitudinal changes in left MTL-left insula connectivity, where an increased insular involvement correlated with visual memory improvement in left ATLR. Additionally in left ATLR, heightened MTL functional couplings with left or right OFC supported visual memory recovery. Orbitofrontal and insular areas are structurally and functionally connected. 30 These regions provide crucial executive control for successful verbal/visual memory formation in healthy controls 31,32 and presurgical TLE. 3,12 Their engagement is heightened under high task’s demand and low memory strength conditions, such as the controlled retrieval of weak memory traces. 33 After right ATLR, contralesional insular and orbitofrontal activations support visual and verbal memory improvement from three to 12 months. 5 Short-term after left ATLR, structural changes in ipsilesional insula and OFC, underlying efficient information transfer, 34 are not yet functionally adaptive, in contrast to contralesional functional and structural plasticity 5,14 . From short-term to 10 years, similar functional connectivity increases ipsilesionally in these regions supported left ATLR visual memory recovery. As such, while plastic trajectory timelines vary between resection groups, they seem to converge to similar outcome: heightened recruitment of highly specialized brain regions for long-term memory convalescence. Strengths and limitations We present a unique longitudinal design spanning many years, in which the same participants have data acquired at four time-points compared to the same control population. Despite a small sample size, we showed statistically significant network changes and correlations. Scanner types differed across follow-ups, however all analyses evaluated differences in patients relative to controls, mitigating scanner-related effects. The specific impact of medication changes on memory dysfunction (e.g., topiramate discontinuation) warrants further investigation in larger replication studies. Healthy controls showed a significant test-retest effect in verbal memory performance noteworthy for short-interval follow-ups, which was absent in patients, likely due to surgical impact on short-term memory function. To our knowledge, this is the first network-level investigation of task-based functional connectivity changes long-term postoperatively with significant clinical implications. Another strength of this study is the use of gPPI as a connectivity tool. This models the entire experimental span, allowing analysis of neural correlates highly specific to subsequent memory effects, and better controls for both type I and II errors compared to other tools such as standard PPI. 35 Conclusion Our longitudinal functional connectivity study investigated the neural mechanisms underlying memory recovery. Memory network plasticity is an ongoing phenomenon that continues to reshape over time. Longitudinal results demonstrated long-term memory connectivity changes in a unique dataset, extending over a decade after ATLR. In our predominantly seizure-free cohort, group-level memory either stabilized or improved in the long-term post-resection. Increases in functional connectivity that supported long-term memory recovery projected to medial temporal and extra-temporal structures. Reduced involvement of the thalamus may serve as an imaging biomarker of cognitive network convalescence. While preliminary, these findings can impact surgical intervention to avoid crucial regions of memory reorganization, shed light on the biology of long-term memory rehabilitation, and advocate ongoing cognitive support strategies to optimize cognitive outcomes years after surgery. Methods Subjects Twenty-five individuals with medically refractory TLE underwent ATLR from 2009 to 2012 at the National Hospital for Neurology and Neurosurgery (NHNN), London, United Kingdom. 5 There were 12 left-sided ATLR (seven males, median preoperative age 38 years, interquartile range (IQR) 28–41) and 13 right-sided (four males, median preoperative age 38 years, IQR 29–50). Neuropsychology assessment, as well as structural and memory functional MRI were acquired at four timepoints: preoperatively, and at a median 3-month (IQR = 3–4) and 12-month (IQR = 11-13.5) post-surgery, and up to 10 years postoperatively (median = 9, IQR = 8–10). Eight left-sided and 10 right-sided ATLR cases completed assessments at all postoperative follow-ups. To optimize acquired data and analysis, a ‘short-term’ assessment timepoint was introduced. It encompassed all data collected at 12 months, alongside data at 3 months from patients unable to attend 12-month follow-up (four left-sided and three right-sided). Throughout this manuscript, ‘short-term’ data refers to assessments conducted during the 3–12-month follow-up period (median = 11 months, IQR = 8–12), occurring from 2009 to 2013. Conversely, 'long-term' data pertains to the 10-year follow-up, conducted between 2019–2022. Ten healthy, English-proficient, matched-controls (four males, aged 27–50) were assessed at similar intervals. Controls and left/right ATLR groups were comparable for language dominance, handedness, sex, and age. All participants provided written informed consent in accordance with the Declaration of Helsinki. The NHNN and Institute of Neurology Joint Research Ethics Committee approved this research (18/LO/1447). Exclusion criteria included contraindication to MRI, non-proficient English speaker, and intelligence quotient (IQ) < 70. Postoperative seizure outcome was assessed using the International League Against Epilepsy (ILAE) classification. 36 Seizure frequency was collected from seizure diaries at preoperative and postoperative time-points; comprising the total number of focal impaired awareness seizures per month and focal to bilateral tonic–clonic seizures. Neuropsychological tests Patients and controls underwent standardized neuropsychometry at corresponding time points; before, at median 3-month and 12-month after surgery, and up to 10 years postoperatively (median 9 years) (see supplementary material for details). Intellectual functioning was evaluated using Full-Scale IQ (FSIQ) of the Wechsler Adult Intelligence Scale (WAIS) 37 in controls, and with the National Adult Reading Test (NART-2) 38 for metrics of premorbid verbal and performance IQ in patients 39 , and reliable estimates of patients’ FSIQ. 40 Patients’ verbal and visual memory was assessed using verbal and design learning subtests of the BIRT Memory and Information Processing Battery version I (BMIPB-I), 41 as previously done, 5,12,39,42 These memory measures are sensitive to temporal structures’ integrity. 43 In controls, BMIPB-I was employed up to January 2021, and BMIPB–II from February 2021 onwards. Memory scores were standardized into z-scores, using ageing norms of corresponding BMIPB version, accounting for version change and age-related differences. 44 Memory change represented the difference between z-scores of short-term and long-term follow-ups. Improvement or decline were considered clinically significant based on reliable change index (RCI) upper and lower limits, using 95% confidence interval, as described in neuropsychological and imaging studies. 14,39,43,44 RCI probes meaningful change by adjusting for test reliability and practice effect in a test-retest context. 44 Magnetic resonance data acquisition Preoperatively and short-term postoperatively, participants were scanned on a 3T GE Signa Excite HDx MRI scanner, with a 20-channel head coil. Long-term postoperatively, data was acquired using 3T GE Discovery MR750, with a 32-channel head coil. Refer to supplementary material for detailed acquisition parameters. Preoperatively and at short-term (long-term) follow-up, memory fMRI timeseries included T2*-weighted gradient echo planar images (EPI) acquired using 36 ( 50 ) contiguous oblique axial slices per volume, 24-cm field of view, 2.5 (2.4) mm slice thickness with 0.3 (0.1) mm gap, with TE of 25 ( 22 ) ms and TR of 2750 ms. 3 At each scanning time-point, the field of view covered the temporal and frontal lobes, and slices were aligned on the sagittal view with the long axis of the hippocampus. 5 Functional memory paradigm We applied the same material-specific memory fMRI paradigm as preoperatively 3,12 , detailed in supplementary material . In summary, black-and-white faces and words were visually presented on a magnetic resonance-compatible screen, viewed through a mirror during a single scanning session at each time-point. Forty minutes after scanning, participants were tested on the same 100 words and faces intermixed with an additional 50 novel words/faces as foils, separately. Participants categorized items as ‘remembered’, ‘familiar’ (if unsure), or ‘novel’ via a button-box, and performance was recorded as either successfully remembered, familiar or forgotten. At each scanning timepoint, an identical memory fMRI paradigm was performed with different items. Data analysis Preprocessing For both 3-12-month and 10-year follow-ups and every subject, the anatomical 3D-T1 scan underwent field bias correction with Advanced Normalization Tools 45 and was registered to a scanner-specific template in MNI space. The scanner-specific template was created from 30 healthy subjects, 15 individuals with left hippocampal sclerosis and 15 people with right hippocampal sclerosis, using high-resolution whole-brain EPI. 3 Short- and long-term functional imaging time-series were realigned to the mean image and time-corrected using Statistical Parametric Mapping 12 (SPM12; http://www.fil.ion.ucl.ac.uk/spm/ ). Normalisation into standard anatomical space was done using EasyReg, 46 a deep-leaning registration method accessible via Freesurfer. 47 Transformation parameters from the T1-to-template registration were used to warp fMRI time-series to template using nearest-neighbour interpolation. Normalized time-series were smoothed on SPM12 using 8mm full-width at half-maximum Gaussian kernel. 42 Longitudinal connectivity analysis Event-related contrasts Event-related spmT maps of subsequent memory effects were generated for each subject and separately for words or faces on SPM12 via random-effects analysis of a blocked design general linear model (GLM). 5 Six regressors of interest were created; words and faces subsequently remembered, familiar, or forgotten. Six motion parameters were added as confounds. Resulting event-related statistical maps were used for subsequent single-level connectivity analyses. MTL seeds To ensure unbiased ROI selection for group comparisons, seed selection was based on AAL-based anatomical masks (WFU-PickAtlas toolbox v3.0). Healthy controls had the left and right hippocampi as MTL seeds, based on their role in successful memory. 3,17 For patients, one MTL seed included the non-resected contralesional hippocampus. Ipsilesionally, the remnant MTL seed entailed remnant hippocampus and parahippocampal gyrus, based on left and right ATLR group resection masks 39,48 . All participants underwent standard ATLR with little within-group difference in the size of resection cavity. Generalized PPI analysis A generalized form of PPI (gPPI) spanned the entire experimental space, 35 modelling beta-estimates of all subsequent memory conditions (further details in supplementary material ). At the participant-level, seed-to-whole-brain connectivity analysis was conducted on MATLAB. 35 For verbal and visual memory separately, the subject-level gPPI model included three regressors: time-course of each event-related task-condition, timeseries of one MTL seed, and of the PPI term (task*seed interaction). All six task-conditions were modelled to better probe successful verbal and visual memory effect. 35 The average seed time-course was extracted within each anatomical MTL mask/seed. Physiological and psychological variables were treated as nuisance regressors. T -contrasts were generated for each MTL seed and words/faces subsequently remembered, revealing whole-brain cortical areas significantly more correlated with the seed during successful memory encoding than during uncertain/failed conditions, based on the PPI term prediction 35 . For each participant, separate GLMs were performed for each MTL seed. The same task and seed regressors were used for all participants and at 3–12-month and 10-year follow-ups. Resulting single-level gPPI t -contrasts of successful subsequent memory were used for group-level random-effects analyses (see below section). Statistical analyses Clinical and neuropsychological data Data was analysed using R 4.0.5. Demographics were evaluated using Fisher’s exact test for sex proportion, one-way ANOVA for parametric z-scores (memory and IQ), and Kruskal–Wallis tests for nonparametric continuous variables (age, ILAE outcomes, ASM intake and change). 42 For multiple comparisons, post-hoc tests were corrected using Tukey's HSD adjustment. Longitudinal assessment of the functional memory network All data was analysed with SPM12. Long-term changes in functional connectivity from 3–12-month to 10-year follow-ups Mixed ANOVAs, using flexible factorial design with IQ as confound regressor, were performed to investigate changes in MTL-seeded memory connectivity between short-term and long-term follow-ups in the individual patient groups compared to changes in test-retest over that timeline in healthy subjects. A distinct analysis was conducted for faces and words successfully remembered, seeding from each MTL separately. For each subject, the relevant first-level gPPI t -contrasts for each of the scanning timepoint (3–12 months and 10 years) were entered. Each flexible factorial design involved a random subject factor, a three-levels group factor (controls, left and right ATLR), and a two-levels condition factor (short-term and long-term postoperative scans), allowing the investigation of a Group x Condition interaction for the successful memory contrasts. Differences in activations across scanning sessions were compared between ATLR groups and controls in t -contrasts: 10-year connectivity > 3–12-month connectivity in left or right ATLR versus controls, and 10-year connectivity < 3–12-month connectivity in left or right ATLR versus controls. In summary, flexible factorial t -contrasts modelled in each ATLR group, the within-subject differences in MTL-seeded, whole-brain functional connectivity across postoperative follow-ups, beyond the connectivity changes seen in controls. Correlation between functional reorganization in TLE and memory recovery Three-way ANCOVAs were conducted for each MTL seed and each successful memory contrast (words/faces), to investigate which differences in functional connectivity from 3–12-month and 10-year follow-ups were related with improvement in memory functions over this timeline. Positive correlations were examined using BMIPB (I or II) verbal and visual learning scores converted into age-normalized z-scores. Difference in z-scores between 3–12-month and 10-year follow-ups was used as continuous variables in three-ways ANCOVAs. Statistical thresholds Given our a priori hypothesis of increased local MTL connectivity (including the fusiform gyrus), 5,9,17 MTL connectivity was corrected for multiple comparisons at P < 0.05 voxel-wise, controlling for family-wise error rate via small volume correction. 5,32,49 This included a 6 mm-radius sphere in contralesional MTL regions, 3,12 and 3 mm-radius sphere in remnant hippocampus and parahippocampal gyrus to avoid resection cavity-related activation. All reported seed-to-remnant hippocampus/parahippocampus connectivity was validated against artifacts using exclusive MTL group-resection masks. Group comparison and correlation analyses generated highly specific MTL-to-whole-brain, longitudinal, event-related t -contrasts. 50 Thus, at the extra-MTL level, functional connectivity is reported at an exploratory P < 0.001 threshold (uncorrected), alike previous longitudinal, event-related and network fMRI studies. 5,12,49 Abbreviations ATLR = anterior temporal lobe resection; ASM = anti-seizure medication; ILAE = International League Against Epilepsy; EPI = echo-planar imaging; F = females; fMRI = functional MRI; fusiform = fusiform gyrus; FWE = family-wise error; G = gyrus; IQ = intelligence quotient; IQR = interquartile range; Inf = inferior; Hippoc. = hippocampus; LGN = lateral geniculate nucleus; M = males; Mid = middle; MTL = medial temporal lobe; N = number; NA = not applicable; NHNN = National Hospital for Neurology and Neurosurgery; Occ= occipital; OFC = orbitofrontal cortex; Operc = operculum; PIQ = performance IQ; Post = Posterior; RCI = reliable change index; Sup = superior; TLE = Temporal Lobe Epilepsy; VIQ = verbal IQ. Declarations Data availability Anonymized data for replication of this study are available from the corresponding author upon reasonable request. Acknowledgements We would like to thank Andrea Hill, Epilepsy Society radiographer, for her crucial help in data collection, Jane de Tisi for gathering long-term clinical information, Gerard Hall for methods discussion, Bernardo Pimentel for clinical discussion, and all our participants for their invaluable cooperation. Funding This work is supported by National Institute for Health Research UCLH Biomedical Research Centre (grant 229811), The Wellcome Trust (grant 083148), Wellcome Trust Innovation Program (106882/Z/15/Z, 218380/Z/19/Z) and MRC (G0802012, MR/M00841X/1). MF and MKS are supported by the UCLH BRC and the Epilepsy Society. PT is supported by a UKRI Future Leaders Fellowship (MR/T04294X/1). This work and MKS are supported by the MRC (grant MR/X031039/1). Author contribution Neuroimage data collection: MF, MKS, LPB, GPW, SBuck. Neuropsychology testing: PJT, SBaxendale, and MF. Conception and study design: MKS and MF. Data processing, statistical analysis, and interpretation: MF, MKS. Physics support: LPB and PT. Neuroimage processing support: LPB. Data analysis support: FX and LPB. Data interpretation support: DG, LG, MKJ, JSD and MKS. Manuscript and supporting materials write-up: MF, MKS. Manuscript preparation support: LPB, PT, FX, DG, LG, GPW, MKJ. Project supervision: MKS and JSD. All authors approved the final manuscript. Competing interests The authors report no competing interests. References Jobst BC, Cascino GD (2015) Resective epilepsy surgery for drug-resistant focal epilepsy: a review. JAMA 313:285–293 Squire LR, Stark CE, Clark RE (2004) The medial temporal lobe. Annu Rev Neurosci 27:279–306. 10.1146/annurev.neuro.27.070203.144130 Sidhu MK et al (2013) A functional magnetic resonance imaging study mapping the episodic memory encoding network in temporal lobe epilepsy. 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Sex M (F) Age Median (IQR) Duration Median (IQR) Seizure Frequency Median (IQR) ILAE Seizure Outcome Anti-Seizure Medications (ASM) T2 T3 T2 to T3 T3 Left ATLR (n = 12) 7 (5) 38 (13) 12.5 (16) 6 (0) Class 1–2: 10 Class 4–5: 2 Class 1: 10 Class 3–5: 2 Less/off: 6 Same: 4 Extra 1–2: 2 None: 4 1–2 ASMs: 7 3 ASMs: 1 Right ATLR (n = 13) 4 (9) 38 (21) 16 (21) 10 (5) Class 1: 11 Class 2–3: 2 Class 1: 12 Class 2: 1 Less/off: 7 Same: 6 None: 6 1–2 ASMs: 6 3 ASMs: 1 Controls (n = 10) 4 (5) 37 (23) NA NA NA NA NA NA P-value 0.40 0.80 0.37 0.91 0.48 0.44 0.76 0.77 Statistical difference between groups is presented, for gender using two-sided Fisher exact p-value, and with Kruskal-Wallis p-values for age, duration, and frequency (all at time of surgery), ILAE outcome and ASM intake. Median (IQR) age and duration at time of surgery are presented in years, while seizure frequency in group median per months. ASM = anti-seizure medications; ATLR= anterior temporal lobe resection; ILAE = International League Against Epilepsy; IQR= interquartile range; F= females; M = males; N = number; NA = not applicable; T2 = 3–12-month follow-up (median 11 months); T3 = 10-year follow-up (median 9 years). Table 2 Neuropsychometry measures across experimental assessments in healthy controls and in left or right resection groups. Preoperative IQ Verbal memory z-scores Visual memory z-scores VIQ PIQ T1 T2 T3 T1 T2 T3 Controls (n = 10) 0.44 (0.69) FSIQ 0.22 (0.78) 1.13 (0.90) 0.55 (1.01) -0.43 (0.88) 0.71 (0.58) 0.83 (0.36) Left ATLR (n = 12) -0.74 (0.60) -0.45 (0.49) -0.72 (1.33) -1.53 (1.55) -0.38 (0.87) 0.08 (0.84) 0.08 (0.84) 0.16 (1.04) Right ATLR (n = 13) -0.70 (0.91) -0.45 (0.77) -1.51 (1.22) -0.84 (1.38) 0.71 (0.50) 0.71 (0.50) -0.77(1.15) -0.33(1.35) P-value 0.001 0.004 0.006 < 0.001 0.029 0.003 0.002 0.076 In controls, full scale IQ (FSIQ) is reported, while in patients, premorbid IQ was assessed via the NART-2; verbal and performance IQ subtests evaluate verbal and non-verbal reasoning. Clinically meaningful changes in z-scores are calculated based on the reliable change index (RCI), using a 95% confidence interval. . For verbal memory from 3–12 months to 10 years, this meant an RCI improvement of ≥ 0.31 and a RCI decline of ≥ 0.40. For visual memory from 3–12 months to 10 years, an RCI improvement of ≥ 0.58 and RCI decline of ≥ 0.16 were deemed clinically significant. All values are shown as mean (standard deviation). P-values are reported for each one-way ANOVA, and significant P -values are shown in bold. ATLR = anterior temporal lobe resection; N = number; T2 = 3–12-month follow-up (median 11 months); T3 = 10-year follow-up (median 9 years); VIQ = verbal IQ; PIQ = performance IQ. Table 3 Functional connectivity changes from 3–12 months to 10 years after anterior temporal lobe resection in people with epilepsy, over and above changes seen in controls. Connectivity T2 to T3 Left ATLR Right ATLR Left MTL seed Right MTL seed Left MTL seed Right MTL seed Words remembered Connectivity increases Left post fusiform (occ.) -34, -84, -14 P = 0.025 a Right post parahippocampal G 18, -42, -6 P = 0.044 a No suprathreshold connectivity Right post fusiform (temp-occ.) 36, -42, -16 P = 0.027 a Left post fusiform (temp-occ.) -24 -42, -14 P = 0.042 a Right post fusiform (occ.) 32, -76, -14 P = 0.027 a Right post parahippocampal G 18, -42, -8 P = 0.040 a Right sub callus of ACC 10, -28, -8 P < 0.001 Connectivity decreases No suprathreshold connectivity Right thalamus (LGN) 18, -28, -4 P < 0.001 No suprathreshold connectivity No suprathreshold connectivity Faces Remembered Connectivity increases Left post parahippocampal G -14, -36, -12 P = 0.018 b Right amygdala 26, 4, -20 P = 0.027 a Left post fusiform (temporal) -38, -26, -16 P = 0.030 a Right post parahippocampal G 26, -28, -22 P = 0.042 b Left post fusiform (temp-occ.) -20, -48, -16 P = 0.001 a Right sup frontal G 18, -10, 60 P = 0.001 Right post fusiform (occ.) 30, -70, -2 P = 0.015 a Left inf temporal G -46, -38, -14 P = 0.001 Right lingual gyrus 28, -72, -2 P < 0.001 Right post fusiform (temp-occ.) 36, -60, -14 P = 0.007 a Right mid fusiform (temporal) 34, -40, -16 P = 0.048 a Connectivity decreases No suprathreshold connectivity No suprathreshold connectivity Left insula -36, 4, -12 P < 0.001 No suprathreshold connectivity T -contrasts results of mixed ANOVAs using a flexible factorial design with IQ as confound variable. The changes in functional connectivity across postoperatively follow-ups are presented in patient groups, over and above changes in controls, seeding from the left and right medial temporal lobes (MTL). MTL-to-neocortex connectivity is displayed at P < 0.001, uncorrected. a P < 0.05, FWE correction, using a 6mm sphere for contralesional MTL regions. b P < 0.05, FWE correction 3mm sphere in remnant MTL regions to avoid resection cavity-related activations. ACC= anterior cingulate cortex; ATLR= anterior temporal lobe resection; Fusiform = fusiform gyrus; FWE = Family Wise Error; G = gyrus; Inf = inferior; LGN= lateral geniculate nucleus; Mid = middle; MTL = medial temporal lobe; Post = posterior; Occ= occipital; Sup = superior; T2 = 3–12-month follow-up (median 11 months); T3 = 10-year follow-up (median 9 years). Table 4 Correlations between long-term verbal memory improvement and longitudinal changes in task-based functional connectivity from 3–12 months to 10 years after anterior temporal lobe resection. Left resection group Right resection group Left MTL seed Right MTL seed Left MTL seed Right MTL seed Connectivity increases T2 to T3 Left post fusiform gyrus -34 -84 -14 P = 0.019 a Right post parahippocampal gyrus 18–42 -6 P = 0.036 a Right post parahippocampal gyrus 36–46 -6 P = 0.049 b Right post fusiform gyrus 36–42 -16 P = 0.012 a Left post fusiform gyrus -26 -44 -12 P = 0.042 a Right post fusiform gyrus 44 − 42 -22 P = 0.020 a Right post parahippocampal gyrus 18–42 -8 P = 0.034 a Right post fusiform gyrus 32–76 -14 P = 0.022 a Connectivity decreases T2 to T3 Left inf parietal gyrus -50 -28 44 P < 0.001 Right thalamus 18–28 -4 P < 0.001 Left sup temporal gyrus -50 -44 20 P = 0.001 Right thalamus 18–28 -4 P = 0.001 Right supramarginal gyrus 66 − 36 24 P = 0.001 Right supramarginal gyrus 66 − 30 26 P < 0.001 Results of three-way ANCOVAs for each MTL seed during encoding of words subsequently remembered. These are the functional connectivity changes from short- to long-term follow-ups in patients that were significantly correlated with improvement in verbal memory z-scores (i.e., from list-learning test) over that timeline. These were analysed relative to connectivity changes and memory of healthy controls. MTL seed to extra-MTL connectivity is displayed at P < 0.001, uncorrected. a P < 0.05, FWE correction, using a 6mm sphere for contralesional MTL regions. b P < 0.05, FWE correction 3mm sphere in remnant MTL regions. FWE = family-wise error; G = gyrus; Inf = inferior; Mid = middle; MTL = medial temporal lobe; Post = Posterior; Sup = superior; T2 = 3–12-month follow-up (median 11 months); T3 = 10-year follow-up (median 9 years). Table 5 Correlations between long-term visual memory improvement and longitudinal changes in task-based functional connectivity from 3–12 months to 10 years after anterior temporal lobe resection. Left resection group Right resection group Left MTL seed Right MTL seed Left MTL seed Right MTL seed Connectivity increases T2 to T3 Left post fusiform G -18 -48 -14 P < 0.001 a Left post hippocampus -22 -36 -2 P = 0.030 b Left post fusiform G -38 -26 -18 P = 0.014 a Left post fusiform G -20 -86 -6 P = 0.046 a Left post fusiform G -34 -64 -10 P = 0.004 a Left mid temporal G -50 -18 -16 P < 0.001 Right post fusiform G 36–64 -14 P = 0.015 a Left post fusiform G -40 -56 -10 P = 0.048 a Right post fusiform G 36–62 -14 P = 0.001 a Right posterior OFC 28 34 − 18 P = 0.001 Right post fusiform G 36–40 -14 P = 0.019 a Left inf temporal G -44 -54 -4 P < 0.001 Left inf temporal G -44 -36 -14 P < 0.001 Right sup frontal G 18 − 10 60 P < 0.001 Right mid temporal G 40–58 16 P = 0.001 Left medial OFC -16 36 − 16 P = 0.001 Right lingual G 24–72 -4 P = 0.001 Left insula -30 18–20 P = 0001 Right mid temporal G 40–56 -16 P < 0.001 Connectivity decreases T2 to T3 No suprathreshold connectivity No suprathreshold connectivity No suprathreshold connectivity No suprathreshold connectivity Results of three-way ANCOVAs for each MTL seed during encoding of faces subsequently remembered. These represent longitudinal connectivity changes in patients that were significantly correlated with improvement in visual memory z-scores (i.e., from design learning test) from short to long-term post-surgery. These analyses were performed relative to connectivity changes and memory of healthy controls. MTL-to-neocortex connectivity is displayed at P < 0.001, uncorrected. a P < 0.05, FWE correction, using a 6mm sphere for contralesional MTL regions. b P < 0.05, FWE correction 3mm sphere in remnant MTL regions. FWE = family-wise error; G = gyrus; Inf = inferior; Mid = middle; MTL = medial temporal lobe; OFC = orbitofrontal cortex; Post = Posterior; Sup = superior; T2 = 3–12-month follow-up (median 11 months); T3 = 10-year follow-up (median 9 years). Additional Declarations There is NO Competing Interest. 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1","display":"","copyAsset":false,"role":"figure","size":350631,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eVerbal and visual memory performance in each resection group and healthy controls at the preoperative, 3–12-month, and 10-year follow-ups.\u003c/strong\u003e In each group, the boxplots and its whiskers show mean, standard error, and maximum and minimum memory z-scores from list and design learning tests, respectively for verbal and visual memory. This was assessed preoperatively, and at the 3–12-months and 10-year follow-ups in patients, and at similar intervals in healthy individuals (i.e., controls). Violin distribution shows the data spread. Memory improvement and decline are determined as clinically significant based on a reliable change index, using 95% confidence interval. ATLR = anterior temporal lobe resection.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-3936758/v1/26e9f5b5a854f0401364c3a5.png"},{"id":51386965,"identity":"385bc668-481d-4781-8070-2adeb6f75c6e","added_by":"auto","created_at":"2024-02-20 17:52:25","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":747497,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eLongitudinal functional connectivity changes correlated with postoperative verbal memory improvement from 3–12 months to 10 years after epilepsy surgery. (A) \u003c/strong\u003eDuring verbal memory fMRI, longitudinal decreases in functional connectivity between the MTL seeds and extra-MTL regions were correlated with long-term verbal memory recovery. Connectivity is represented via dark blue connecting-lines between each seed (dark-blue spheres) and cortical regions (fMRI clusters in dark-blue), and at\u003cem\u003e P\u003c/em\u003e \u0026lt; 0.001, uncorrected.\u003cstrong\u003e (B) \u003c/strong\u003eFor verbal memory fMRI, longitudinal connectivity increases between the MTL seeds and right parahippocampal gyrus supported verbal memory improvement from 3–12 months to 10 years. Medial temporal activations are presented at \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05, family-wise error small volume corrected. ATLR = anterior temporal lobe resection; L = left; MTL = medial temporal lobe; R = right; SupraM = supramarginal gyrus.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-3936758/v1/55ba8fae43ae14c7222e6847.png"},{"id":51386968,"identity":"de9b3d08-5645-4429-a95b-2b4797cfe8a1","added_by":"auto","created_at":"2024-02-20 17:52:25","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":642655,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eLongitudinal functional connectivity changes correlated with postoperative visual memory improvement from 3–12 months to 10 years after epilepsy surgery. (A) \u003c/strong\u003eFor visual memory fMRI, longitudinal increases in functional connectivity across follow-ups between the MTL seeds and extra-MTL regions supported long-term visual memory recovery. Connectivity is represented via cyan blue connecting-lines between each seed (cyan-blue spheres) and cortical regions (fMRI clusters in cyan-blue), and at\u003cem\u003e P\u003c/em\u003e\u0026lt; 0.001, uncorrected.\u003cstrong\u003e \u003c/strong\u003e\u0026nbsp;\u003cstrong\u003e(B) \u003c/strong\u003eFor visual memory fMRI, longitudinal connectivity increases between left MTL seed and bilateral fusiform gyrus correlated with improved visual memory from 3-12 months to 10 years. Medial temporal activations are presented at \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05, family-wise error small volume corrected. L = left; MTL = medial temporal lobe; OFC = orbitofrontal cortex; R = right.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-3936758/v1/f308aa121235a1b5f4f0cb27.png"},{"id":73941593,"identity":"76ad870b-75d2-4b90-8382-3a3fc3e7a05e","added_by":"auto","created_at":"2025-01-16 08:06:52","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3357024,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3936758/v1/a3c70538-3115-48fc-99ea-d899bf7b3539.pdf"},{"id":51386967,"identity":"0510ff9f-1871-475e-a602-2ae8b0e915ee","added_by":"auto","created_at":"2024-02-20 17:52:25","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":51186,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterial1yto10yNatureComm.docx","url":"https://assets-eu.researchsquare.com/files/rs-3936758/v1/f40e855ddef5bf0e9c3c26eb.docx"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Long-Term Memory Plasticity: A Decade-Long Connectivity Study Post Anterior Temporal Lobe Resection","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAnterior temporal lobe resection (ATLR) is the most commonly performed surgical treatment for medically intractable temporal lobe epilepsy (TLE).\u003csup\u003e1\u003c/sup\u003e This involves the partial removal of temporal neocortical and mesial temporal structures including the anterior hippocampus, parahippocampal and fusiform gyri; structures critical for successful memory formation.\u003csup\u003e2,3\u003c/sup\u003e Concordantly, noteworthy episodic memory deficit affects up to 40% of people with epilepsy (PWE) postoperatively.\u003csup\u003e1,4\u003c/sup\u003e Identifying regions crucial for effective memory reorganization that may be spared during epilepsy surgery may help mitigate against memory loss caused by surgical intervention. Additionally, understanding post-operative plasticity could assist the development of strategies to promote long-term memory recovery.\u003c/p\u003e \u003cp\u003eLongitudinal functional MRI (fMRI) studies have highlighted plasticity of episodic memory function up to 2 years following ATLR.\u003csup\u003e5,6\u003c/sup\u003e Existing task-based fMRI research primarily compared mid-term (up to 2 years) postoperative memory activations with preoperative or short-term (3 months) post-surgical activations.\u003csup\u003e5\u0026ndash;8\u003c/sup\u003e These showed that increased engagement of contralateral hippocampus and neocortex, including the insula and orbitofrontal cortex (OFC), was supportive of postoperative memory function in PWE.\u003csup\u003e5,7,9\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eNetwork-level analyses however have only been performed on resting-state fMRI.\u003csup\u003e10,11\u003c/sup\u003e Task-based fMRI connectomics is needed to comprehensively model postoperative changes in the functional architecture of episodic memory and its association with memory function following ATLR. This comes in light of recent evidence of distributed functional\u003csup\u003e5,8,12\u003c/sup\u003e and structural alterations\u003csup\u003e13,14\u003c/sup\u003e before and after ATLR, together with widespread postoperative deficits across verbal and non-verbal memory domains, regardless of surgical laterality.\u003csup\u003e15\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eNetwork studies using psychophysiological interaction (PPI)\u003csup\u003e16\u003c/sup\u003e analysis model the changes in functional couplings between a seed and whole-brain regions specific to task performance. Using PPI, we previously showed widespread functional connectivity increases in TLE between bilateral medial temporal lobes (MTLs) and to contralesional temporal and extra-temporal regions that supported better memory.\u003csup\u003e12\u003c/sup\u003e Investigating longitudinal connectivity changes specific to the memory connectome would inform on the network\u0026rsquo;s potential for adaptive plasticity beyond the two-year postoperative mark.\u003c/p\u003e \u003cp\u003eA critical research question emerges; whether memory functional plasticity after surgery represents a short-term response to surgical insult, or is an ongoing, dynamic process that evolves over time. If plasticity is indeed an ongoing phenomenon, identifying patterns of memory-node abnormalities in longitudinal studies may shed light on the biology of rehabilitation and aid stratifying patients for optimal cognitive support strategies. Additionally, comprehending the long-term memory outcome and its supporting network is vital for effective pre-operative counselling of PWE and their families.\u003c/p\u003e \u003cp\u003eThis study aimed to identify neural mechanisms underlying verbal and visual memory network plasticity and recovery long-term after epilepsy surgery. In a longitudinal design, we (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) assessed changes in task-associated functional connectivity from 3\u0026ndash;12 months to 10 years after ATLR using generalized PPI, and (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) correlated memory network alterations with improvement in episodic memory function. We hypothesized that there will be continued long-term plasticity of episodic memory networks\u003csup\u003e5,17\u003c/sup\u003e, particularly adaptive in people who are rendered seizure-free post-operatively\u003csup\u003e15\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eGiven our previous research and short-term plasticity effects, changes in local MTL connectivity including connections to the fusiform gyrus are of \u003cem\u003ea priori\u003c/em\u003e interest\u003csup\u003e5,9,17\u003c/sup\u003e.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe study cohort was followed-up 3 months, 12 months, and 10 years after ATLR (and similar in controls). \u0026apos;Short-term\u0026apos; and \u0026apos;long-term\u0026apos; respectively denote a combined 3\u0026ndash;12-month (median\u0026thinsp;=\u0026thinsp;11, interquartile range (IQR)\u0026thinsp;=\u0026thinsp;8\u0026ndash;12) timepoint and a 10-year (median\u0026thinsp;=\u0026thinsp;9, IQR\u0026thinsp;=\u0026thinsp;8\u0026ndash;10) follow-up.\u003c/p\u003e\n\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003eSubjects\u003c/h2\u003e\n \u003cp\u003ePatient demographics and clinical features at 3\u0026ndash;12 months and 10 years are outlined Table\u0026nbsp;1. Long-term postoperatively, seizure-freedom (i.e., ILAE outcome 1) was observed in 83% of left and 92% of right ATLR.\u003c/p\u003e\n \u003cp\u003eKruskal-Wallis and two-sided Fisher exact tests respectively showed non-significant differences in age and sex between patient and control groups (Table\u0026nbsp;1). There was no significant difference between both patient groups in clinical features (using Kruskal-Wallis tests).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n \u003ch2\u003ePostoperative neuropsychology\u003c/h2\u003e\n \u003cdiv id=\"Sec5\" class=\"Section3\"\u003e\n \u003ch2\u003eLong-term memory change\u003c/h2\u003e\n \u003cp\u003eLongitudinal changes in memory were determined as clinically significant based on a reliable change index (RCI), using 95% confidence interval.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n \u003ch2\u003eHealthy controls\u003c/h2\u003e\n \u003cp\u003eFrom 3\u0026ndash;12 months to 10 years, healthy controls\u0026rsquo; memory was as follows: for verbal memory, 12.5% improved, 12.5% no change, while 75% declined; for visual memory, 12.5% improved, 50% no change, while 37.5% declined. At the group-level, there was a clinically significant improvement in verbal memory from preoperative to 3\u0026ndash;12 months timepoints, which was reversed from 3\u0026ndash;12 months to 10 years (i.e., significant decline). For visual memory, group-level performance remained stable over time.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n \u003ch2\u003eLeft ATLR\u003c/h2\u003e\n \u003cp\u003eIn left ATLR, clinically significant changes in postoperative memory from 3\u0026ndash;12-month to 10-year assessments were as follows: for verbal memory, 50% improved, 17% showed no change, while 33% declined; for visual memory, 42% improved, 8% remained stable, while 50% declined.\u003c/p\u003e\n \u003cp\u003eAt the group-level, verbal memory performance was stable from preoperative to 3\u0026ndash;12-month follow-ups, while there was a clinically significant improvement from 3\u0026ndash;12-months to 10 years. At the 10-year follow-up compared to preoperatively, 75% of left ATLR patients demonstrated positive outcomes in verbal memory, with 33% returning to baseline performance and 42% showing improved memory. Visual memory significantly improved from preoperative to 3\u0026ndash;12-month assessments and remained stable to the longer term (Fig.\u0026nbsp;1).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003eRight ATLR\u003c/h2\u003e\n \u003cp\u003eClinically significant changes in right ATLR were as follows: for verbal memory, 31% improved, 46% no change, while 23% declined; for visual memory, 38% improved, 15% no change, while 38% declined.\u003c/p\u003e\n \u003cp\u003eAt the group-level from preoperative to 3\u0026ndash;12-month assessments, there was an initial visual memory decline that resolved in the longer-term: group-average increased from 3\u0026ndash;12 months to 10 years despite not reaching significance (Fig. 1 and Table 2). Ten years postoperatively relative to preoperatively, 58% of right ATLR patients showed positive outcomes in visual memory, with 33% returning to baseline performance and 25% exhibiting better memory. For verbal memory, group-level performance remained stable over time.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n \u003ch2\u003eGroup difference in memory outcome\u003c/h2\u003e\n \u003cp\u003eOne-way ANOVAs were used on parametric z-scores and post-hoc tests were corrected using Tukey\u0026apos;s Honestly Significant Difference (HSD) adjustment. Group averages in memory z-scores and statistics are shown Table\u0026nbsp;2 (\u003cem\u003esupplementary material\u003c/em\u003e details preoperative neuropsychology and confidence intervals).\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eThree\u0026ndash;12 months\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eShort-term postoperatively, healthy individuals\u0026rsquo; verbal memory was significantly better than that of left ATLR (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and right ATLR (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004). For visual memory, controls performed significantly better than right ATLR (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002) but not left ATLR (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.25).\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTen years\u003c/strong\u003e: Long-term postoperatively, controls\u0026rsquo; verbal memory was significantly greater than in left ATLR (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.028) but not right ATLR (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.076). There was no significant difference in long-term visual memory between control and patient groups (left ATLR \u003cem\u003evs\u003c/em\u003e. controls: \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.36; right ATLR \u003cem\u003evs\u003c/em\u003e. controls: \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.061).\u003c/p\u003e\n \u003cp\u003eAcross postoperative timepoints, there was no significant difference in verbal or visual memory z-scores between ATLR groups (see \u003cem\u003esupplementary material\u003c/em\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n \u003ch2\u003eChanges in functional connectivity 3\u0026ndash;12 months to 10 years post-surgery relative to changes in controls\u003c/h2\u003e\n \u003cp\u003eTable\u0026nbsp;3 shows detailed results from the flexible factorial design analysis.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003eLeft ATLR relative to controls\u003c/h2\u003e\n \u003cdiv id=\"Sec12\" class=\"Section3\"\u003e\n \u003ch2\u003eWords remembered\u003c/h2\u003e\n \u003cp\u003eFrom 3\u0026ndash;12 months to 10 years after left ATLR, there was increased connectivity between both MTL seeds and contralesional posterior parahippocampal gyrus, and between remnant left MTL and remnant posterior fusiform gyrus. Extra-temporally, connectivity was longitudinally increased between the remnant MTL and right anterior cingulate cortex, but significantly decreased between the contralesional hippocampal seed and right thalamus.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n \u003ch2\u003eFaces remembered\u003c/h2\u003e\n \u003cp\u003eLong-term compared to short-term after left ATLR, there was enhanced functional connectivity between the remnant left MTL and remnant parahippocampal and bilateral posterior fusiform gyri, and between the contralesional hippocampal seed and right amygdala. Neocortically, there was increased connectivity between the remnant MTL and left inferior temporal gyrus, and between the contralesional hippocampal seed and right superior frontal gyrus from 3\u0026ndash;12 months to 10 years.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\n \u003ch2\u003eRight ATLR relative to controls\u003c/h2\u003e\n \u003cdiv id=\"Sec15\" class=\"Section3\"\u003e\n \u003ch2\u003eWords remembered\u003c/h2\u003e\n \u003cp\u003eFunctional connectivity long-term compared to short-term after right ATLR was increased ipsilesionally, between remnant right MTL seed and remnant fusiform gyrus. There was no significant MTL-to-neocortex change in functional connectivity.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\n \u003ch2\u003eFaces remembered\u003c/h2\u003e\n \u003cp\u003eFunctional connectivity from 3\u0026ndash;12 months to 10 years after right ATLR was enhanced between the contralesional hippocampal seed and bilateral posterior fusiform gyri, and between the remnant right MTL seed and right posterior parahippocampal gyrus. Extra-temporally, the contralesional hippocampal seed showed stronger functional couplings with right lingual gyrus, and reduced connectivity with the left insula, long-term relative to short-term post-surgery.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\n \u003ch2\u003eCorrelation between longitudinal changes in connectivity and memory recovery 3\u0026ndash;12 months to 10 years postoperatively\u003c/h2\u003e\n \u003cp\u003eGeneralized PPI analyses inherently modelled memory-encoding networks underlying successful memory formation. Therefore, all reported activations represent connectivity that is supportive of memory function. To look at neural substrates of more efficient memory recovery, correlations were performed, revealing the most adaptive longitudinal connectivity changes. Longitudinal changes in task-based connectivity significantly correlated with improvement in memory z-scores from 3\u0026ndash;12 months to 10 years are presented in Fig. \u0026nbsp;2 and Table 4 for verbal memory, and Fig. 3 and Table 5 for visual memory in both resection groups.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\n \u003ch2\u003eLeft ATLR relative to controls\u003c/h2\u003e\n \u003cdiv id=\"Sec19\" class=\"Section3\"\u003e\n \u003ch2\u003eWords remembered\u003c/h2\u003e\n \u003cp\u003eFrom 3\u0026ndash;12 months to 10 years after left ATLR, improvement in verbal memory was significantly correlated with increased functional connectivity between both MTL seeds and the right posterior parahippocampal gyrus, and between the remnant left MTL seed and remnant posterior fusiform gyrus.\u003c/p\u003e\n \u003cp\u003eAt the extra-MTL level, verbal memory improvement was significantly associated with reduced long-term connectivity between remnant left MTL and left parietal gyrus, and between the contralesional hippocampal seed and right supramarginal gyrus and thalamus, 10 years relative to 3\u0026ndash;12 months post-surgery.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec20\" class=\"Section2\"\u003e\n \u003ch2\u003eFaces remembered\u003c/h2\u003e\n \u003cp\u003eShort relative to long-term after left ATLR, longitudinal increases in connectivity between the remnant left MTL seed and bilateral posterior fusiform gyri and between the contralesional hippocampal seed and remnant hippocampus significantly supported visual memory improvement.\u003c/p\u003e\n \u003cp\u003eNeocortically, visual memory improvement was significantly correlated with longitudinal enhancement of bilateral fronto-temporal connectivity; between remnant MTL and left OFC, left insula and bilateral temporal cortex, and between contralesional hippocampal seed and left middle temporal gyrus, right OFC, and right superior frontal gyrus.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec21\" class=\"Section2\"\u003e\n \u003ch2\u003eRight ATLR relative to controls\u003c/h2\u003e\n \u003cdiv id=\"Sec22\" class=\"Section3\"\u003e\n \u003ch2\u003eWords remembered\u003c/h2\u003e\n \u003cp\u003eSimilar to left ATLR, from 3\u0026ndash;12 months to 10 years after right ATLR verbal memory improvement was significantly correlated with increased connectivity between remnant right MTL seed and remnant posterior fusiform gyri, and between the contralesional left hippocampal seed and remnant parahippocampal gyrus.\u003c/p\u003e\n \u003cp\u003eAt the extra-MTL level, long-term verbal memory improvement was significantly supported by reduced connectivity between contralesional left hippocampus and left temporal cortex, and between the remnant MTL and right supramarginal gyrus and right thalamus.\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv id=\"Sec23\" class=\"Section3\"\u003e\n \u003ch2\u003eFaces remembered\u003c/h2\u003e\n \u003cp\u003eFrom short to long-term after right ATLR, longitudinal increases in functional connectivity between the remnant right MTL and contralesional posterior fusiform, and between contralesional hippocampal seed and bilateral fusiform gyri were supportive of long-term visual memory improvement.\u003c/p\u003e\n \u003cp\u003eAt the extra-MTL level, improvement in visual memory significantly correlated with increased functional connections between the contralesional hippocampal seed and right lingual and middle temporal gyri, and between the remnant MTL and contralesional inferior temporal gyrus, 10 years compared to 3\u0026ndash;12 months after right ATLR.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis longitudinal study explored neural processes underlying memory network recovery long-term after anterior temporal lobe resection. Patient-specific connectivity changes of the episodic memory-encoding network were (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) assessed from 3\u0026ndash;12 months to 10 years postoperatively relative to changes in healthy controls, and (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) correlated with improvement in long-term verbal and visual memory function.\u003c/p\u003e \u003cp\u003eOur findings revealed key increases in functional connections over the long term, to posterior MTL regions including the right posterior parahippocampal gyrus and remnant /bilateral posterior fusiform gyri. These changes were central to verbal and visual memory recovery from 3\u0026ndash;12 months to 10 years after ATLR. Reduced thalamo-MTL connectivity and stronger connections to the bilateral orbitofrontal cortex (OFC) and left insula, 10 years relative to 3\u0026ndash;12 months postoperatively, supported improvement in late verbal and visual memory, respectively.\u003c/p\u003e \u003cdiv id=\"Sec25\" class=\"Section2\"\u003e \u003ch2\u003eLong-term postoperative memory changes\u003c/h2\u003e \u003cp\u003eIn intractable TLE, recurrent seizures and increasing drug load negatively impact mood, cognition, and integrity of memory-related brain regions.\u003csup\u003e18,19\u003c/sup\u003e In this study, most postsurgical PWE achieved seizure freedom, and approximately half reduced or ceased ASMs across follow-ups (50% left, 54% right ATLR).\u003c/p\u003e \u003cp\u003e From before to 3\u0026ndash;12-months post-ATLR, healthy controls exhibited a verbal memory learning/test-retest effect that was absent in postsurgical PWE, suggesting an immediate surgical insult on cognitive function. \u003csup\u003e15,20\u003c/sup\u003e Beyond 3\u0026ndash;12 months, our predominantly seizure-free cohort demonstrated cognitive stability at the group-level, consistent with neuropsychological research, reviewed here.\u003csup\u003e21\u003c/sup\u003e\u003c/p\u003e \u003cp\u003ePatient-specific recovery is however evident over the long term. From 3\u0026ndash;12-months to 10 years, 50% of left ATLR and 38% of right ATLR showed clinically significant improvement in verbal and visual memory, respectively. Visual memory improved in people who had left-sided resection, with group-level performance significantly increasing above baseline within the first year post-surgery and stabilizing over the longer term. Ten years postoperatively, 75% of left ATLR and 58% of right ATLR had good verbal and visual memory outcomes compared to preoperatively, with improved performance or return to baseline. Enhancement of baseline performance possibly translates to successful nociferous cortex removal and corresponding release of functions and reserve capacities previously suppressed by ongoing seizures\u003csup\u003e22,23\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThis has important clinical implications for presurgical discussion and cognitive rehabilitation endorsement.\u003csup\u003e24\u003c/sup\u003e Our findings demonstrate that ATLR facilitates long-term medication reduction, sustained seizure freedom, and related cognitive stabilization or improvement long-term post-operation.\u003csup\u003e15\u003c/sup\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec26\" class=\"Section2\"\u003e \u003ch2\u003eMedial temporal plasticity over a decade postoperatively\u003c/h2\u003e \u003cp\u003eNeuroimaging evidence demonstrates the role of posterior MTL regions in subsequent verbal memory formation, with heightened engagement in TLE.\u003csup\u003e3,12,25\u003c/sup\u003e Our findings showed that from 3\u0026ndash;12 months to 10 years postoperatively, long-term reorganization toward posterior fusiform and right posterior parahippocampal gyri was significantly supportive of postoperative improvement in visual and verbal memory.\u003c/p\u003e \u003cp\u003e Among left and right ATLR patients, those with stronger verbal memory improvement across follow-ups exhibited stronger increases in connectivity between left MTL and right posterior parahippocampal gyrus, alongside ipsilesional fusiform connectivity (remnant seed\u0026ndash;remnant fusiform). Similarly, long-term visual memory improvement from 3\u0026ndash;12 months to 10 years was significantly correlated with extensive increases in left MTL\u0026ndash;bilateral fusiform connectivity.\u003c/p\u003e \u003cp\u003eActivation-based fMRI studies have denoted postoperative plasticity effects to the contralesional hippocampus within one year post-ATLR.\u003csup\u003e5,7\u003c/sup\u003e Using network analyses, we reveal that longer-term plasticity involves a more bilaterally connected medial temporal network invariant of surgical laterality, thereby challenging traditional concepts of domain-specific functional lateralization.\u003c/p\u003e \u003cp\u003eLong-term after ATLR, the importance of successful network reorganization toward structures that putatively underly the processing and specialized pattern recognition of graphic and contextual stimuli is emphasized.\u003csup\u003e25,26\u003c/sup\u003e Enhancing their integration with the broader brain network through preoperative pre-habilitation and postoperative rehabilitation presents a promising clinical avenue to facilitate long-term cognitive recovery.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec27\" class=\"Section2\"\u003e \u003ch2\u003eReduced thalamic recruitment and verbal memory recovery\u003c/h2\u003e \u003cp\u003e Reduced thalamic recruitment is associated with verbal memory improvement from 3\u0026ndash;12 months to 10 years after ATLR. Specifically, longitudinal decreases in functional couplings between left MTL\u0026ndash;left parietal/temporal cortex and right MTL\u0026ndash;right supramarginal gyrus, along with ongoing reduction in right MTL-right thalamic connectivity correlated significantly with long-term verbal memory recovery, irrespective of lesion side.\u003c/p\u003e \u003cp\u003eThe thalamus plays a crucial role in ictogenesis\u003csup\u003e27\u003c/sup\u003e and seizure propagation.\u003csup\u003e28\u003c/sup\u003e The nociferous cortex hypothesis suggests that chronic epilepsy disrupts extra-temporal regions through abnormal epileptiform activity propagation,\u003csup\u003e22\u003c/sup\u003e and successful removal of epileptogenic cortex, leading to seizure-freedom, is associated with cognitive improvement.\u003csup\u003e10,15\u003c/sup\u003e The thalamus correspondingly modulates task performance, with a reduced task-related engagement in healthy controls that is maladaptively heightened in active generalized epilepsy.\u003csup\u003e28,29\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eLongitudinal decreases in MTL-seeded thalamic and extra-temporal connectivity may serve as an imaging biomarker of memory network convalescence, coinciding with nociferous cortex removal and seizure cessation. Future studies should explore whether reduced thalamic and extra-temporal connectivity corresponds to expected gains in executive function.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec28\" class=\"Section2\"\u003e \u003ch2\u003eFrontal plasticity and visual memory recovery\u003c/h2\u003e \u003cp\u003eFrom 3\u0026ndash;12 months to 10 years postoperatively, heightened extra-MTL engagement offers computational support during successful visual encoding. This was especially evident through the longitudinal changes in left MTL-left insula connectivity, where an increased insular involvement correlated with visual memory improvement in left ATLR. Additionally in left ATLR, heightened MTL functional couplings with left or right OFC supported visual memory recovery.\u003c/p\u003e \u003cp\u003eOrbitofrontal and insular areas are structurally and functionally connected.\u003csup\u003e30\u003c/sup\u003e These regions provide crucial executive control for successful verbal/visual memory formation in healthy controls\u003csup\u003e31,32\u003c/sup\u003e and presurgical TLE.\u003csup\u003e3,12\u003c/sup\u003e Their engagement is heightened under high task\u0026rsquo;s demand and low memory strength conditions, such as the controlled retrieval of weak memory traces.\u003csup\u003e33\u003c/sup\u003e After right ATLR, contralesional insular and orbitofrontal activations support visual and verbal memory improvement from three to 12 months.\u003csup\u003e5\u003c/sup\u003e Short-term after left ATLR, structural changes in ipsilesional insula and OFC, underlying efficient information transfer,\u003csup\u003e34\u003c/sup\u003e are not yet functionally adaptive, in contrast to contralesional functional and structural plasticity\u003csup\u003e5,14\u003c/sup\u003e. From short-term to 10 years, similar functional connectivity increases ipsilesionally in these regions supported left ATLR visual memory recovery.\u003c/p\u003e \u003cp\u003eAs such, while plastic trajectory timelines vary between resection groups, they seem to converge to similar outcome: heightened recruitment of highly specialized brain regions for long-term memory convalescence.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec29\" class=\"Section2\"\u003e \u003ch2\u003eStrengths and limitations\u003c/h2\u003e \u003cp\u003eWe present a unique longitudinal design spanning many years, in which the same participants have data acquired at four time-points compared to the same control population. Despite a small sample size, we showed statistically significant network changes and correlations. Scanner types differed across follow-ups, however all analyses evaluated differences in patients relative to controls, mitigating scanner-related effects. The specific impact of medication changes on memory dysfunction (e.g., topiramate discontinuation) warrants further investigation in larger replication studies. Healthy controls showed a significant test-retest effect in verbal memory performance noteworthy for short-interval follow-ups, which was absent in patients, likely due to surgical impact on short-term memory function.\u003c/p\u003e \u003cp\u003eTo our knowledge, this is the first network-level investigation of task-based functional connectivity changes long-term postoperatively with significant clinical implications. Another strength of this study is the use of gPPI as a connectivity tool. This models the entire experimental span, allowing analysis of neural correlates highly specific to subsequent memory effects, and better controls for both type I and II errors compared to other tools such as standard PPI.\u003csup\u003e35\u003c/sup\u003e\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur longitudinal functional connectivity study investigated the neural mechanisms underlying memory recovery. Memory network plasticity is an ongoing phenomenon that continues to reshape over time. Longitudinal results demonstrated long-term memory connectivity changes in a unique dataset, extending over a decade after ATLR. In our predominantly seizure-free cohort, group-level memory either stabilized or improved in the long-term post-resection. Increases in functional connectivity that supported long-term memory recovery projected to medial temporal and extra-temporal structures. Reduced involvement of the thalamus may serve as an imaging biomarker of cognitive network convalescence. While preliminary, these findings can impact surgical intervention to avoid crucial regions of memory reorganization, shed light on the biology of long-term memory rehabilitation, and advocate ongoing cognitive support strategies to optimize cognitive outcomes years after surgery.\u003c/p\u003e "},{"header":"Methods","content":"\u003cdiv id=\"Sec31\" class=\"Section2\"\u003e\u003cdiv id=\"Sec32\" class=\"Section3\"\u003e \u003ch2\u003eSubjects\u003c/h2\u003e \u003cp\u003eTwenty-five individuals with medically refractory TLE underwent ATLR from 2009 to 2012 at the National Hospital for Neurology and Neurosurgery (NHNN), London, United Kingdom.\u003csup\u003e5\u003c/sup\u003e There were 12 left-sided ATLR (seven males, median preoperative age 38 years, interquartile range (IQR) 28\u0026ndash;41) and 13 right-sided (four males, median preoperative age 38 years, IQR 29\u0026ndash;50).\u003c/p\u003e \u003cp\u003eNeuropsychology assessment, as well as structural and memory functional MRI were acquired at four timepoints: preoperatively, and at a median 3-month (IQR\u0026thinsp;=\u0026thinsp;3\u0026ndash;4) and 12-month (IQR\u0026thinsp;=\u0026thinsp;11-13.5) post-surgery, and up to 10 years postoperatively (median\u0026thinsp;=\u0026thinsp;9, IQR\u0026thinsp;=\u0026thinsp;8\u0026ndash;10). Eight left-sided and 10 right-sided ATLR cases completed assessments at all postoperative follow-ups.\u003c/p\u003e \u003cp\u003eTo optimize acquired data and analysis, a \u0026lsquo;short-term\u0026rsquo; assessment timepoint was introduced. It encompassed all data collected at 12 months, alongside data at 3 months from patients unable to attend 12-month follow-up (four left-sided and three right-sided). Throughout this manuscript, \u0026lsquo;short-term\u0026rsquo; data refers to assessments conducted during the 3\u0026ndash;12-month follow-up period (median\u0026thinsp;=\u0026thinsp;11 months, IQR\u0026thinsp;=\u0026thinsp;8\u0026ndash;12), occurring from 2009 to 2013. Conversely, 'long-term' data pertains to the 10-year follow-up, conducted between 2019\u0026ndash;2022.\u003c/p\u003e \u003cp\u003eTen healthy, English-proficient, matched-controls (four males, aged 27\u0026ndash;50) were assessed at similar intervals. Controls and left/right ATLR groups were comparable for language dominance, handedness, sex, and age.\u003c/p\u003e \u003cp\u003e All participants provided written informed consent in accordance with the Declaration of Helsinki. The NHNN and Institute of Neurology Joint Research Ethics Committee approved this research (18/LO/1447). Exclusion criteria included contraindication to MRI, non-proficient English speaker, and intelligence quotient (IQ)\u0026thinsp;\u0026lt;\u0026thinsp;70. Postoperative seizure outcome was assessed using the International League Against Epilepsy (ILAE) classification.\u003csup\u003e36\u003c/sup\u003e Seizure frequency was collected from seizure diaries at preoperative and postoperative time-points; comprising the total number of focal impaired awareness seizures per month and focal to bilateral tonic\u0026ndash;clonic seizures.\u003c/p\u003e \u003cdiv id=\"Sec33\" class=\"Section4\"\u003e \u003ch2\u003eNeuropsychological tests\u003c/h2\u003e \u003cp\u003ePatients and controls underwent standardized neuropsychometry at corresponding time points; before, at median 3-month and 12-month after surgery, and up to 10 years postoperatively (median 9 years) (see \u003cem\u003esupplementary material\u003c/em\u003e for details).\u003c/p\u003e \u003cp\u003eIntellectual functioning was evaluated using Full-Scale IQ (FSIQ) of the Wechsler Adult Intelligence Scale (WAIS)\u003csup\u003e37\u003c/sup\u003e in controls, and with the National Adult Reading Test (NART-2)\u003csup\u003e38\u003c/sup\u003e for metrics of premorbid verbal and performance IQ in patients\u003csup\u003e39\u003c/sup\u003e, and reliable estimates of patients\u0026rsquo; FSIQ.\u003csup\u003e40\u003c/sup\u003e Patients\u0026rsquo; verbal and visual memory was assessed using verbal and design learning subtests of the BIRT Memory and Information Processing Battery version I (BMIPB-I),\u003csup\u003e41\u003c/sup\u003e as previously done,\u003csup\u003e5,12,39,42\u003c/sup\u003e These memory measures are sensitive to temporal structures\u0026rsquo; integrity.\u003csup\u003e43\u003c/sup\u003e In controls, BMIPB-I was employed up to January 2021, and BMIPB\u0026ndash;II from February 2021 onwards.\u003c/p\u003e \u003cp\u003eMemory scores were standardized into z-scores, using ageing norms of corresponding BMIPB version, accounting for version change and age-related differences.\u003csup\u003e44\u003c/sup\u003e Memory change represented the difference between z-scores of short-term and long-term follow-ups. Improvement or decline were considered clinically significant based on reliable change index (RCI) upper and lower limits, using 95% confidence interval, as described in neuropsychological and imaging studies.\u003csup\u003e14,39,43,44\u003c/sup\u003e RCI probes meaningful change by adjusting for test reliability and practice effect in a test-retest context.\u003csup\u003e44\u003c/sup\u003e\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec34\" class=\"Section3\"\u003e \u003ch2\u003eMagnetic resonance data acquisition\u003c/h2\u003e \u003cp\u003ePreoperatively and short-term postoperatively, participants were scanned on a 3T GE Signa Excite HDx MRI scanner, with a 20-channel head coil. Long-term postoperatively, data was acquired using 3T GE Discovery MR750, with a 32-channel head coil. Refer to \u003cem\u003esupplementary material\u003c/em\u003e for detailed acquisition parameters.\u003c/p\u003e \u003cp\u003ePreoperatively and at short-term (long-term) follow-up, memory fMRI timeseries included T2*-weighted gradient echo planar images (EPI) acquired using 36 (\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e) contiguous oblique axial slices per volume, 24-cm field of view, 2.5 (2.4) mm slice thickness with 0.3 (0.1) mm gap, with TE of 25 (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) ms and TR of 2750 ms.\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAt each scanning time-point, the field of view covered the temporal and frontal lobes, and slices were aligned on the sagittal view with the long axis of the hippocampus.\u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e\n\u003ch3\u003eFunctional memory paradigm\u003c/h3\u003e\n\u003cp\u003eWe applied the same material-specific memory fMRI paradigm as preoperatively\u003csup\u003e3,12\u003c/sup\u003e, detailed in \u003cem\u003esupplementary material\u003c/em\u003e.\u003c/p\u003e \u003cp\u003eIn summary, black-and-white faces and words were visually presented on a magnetic resonance-compatible screen, viewed through a mirror during a single scanning session at each time-point. Forty minutes after scanning, participants were tested on the same 100 words and faces intermixed with an additional 50 novel words/faces as foils, separately. Participants categorized items as \u0026lsquo;remembered\u0026rsquo;, \u0026lsquo;familiar\u0026rsquo; (if unsure), or \u0026lsquo;novel\u0026rsquo; via a button-box, and performance was recorded as either successfully remembered, familiar or forgotten. At each scanning timepoint, an identical memory fMRI paradigm was performed with different items.\u003c/p\u003e \u003cdiv id=\"Sec36\" class=\"Section2\"\u003e \u003ch2\u003eData analysis\u003c/h2\u003e \u003cdiv id=\"Sec37\" class=\"Section3\"\u003e \u003ch2\u003ePreprocessing\u003c/h2\u003e \u003cp\u003eFor both 3-12-month and 10-year follow-ups and every subject, the anatomical 3D-T1 scan underwent field bias correction with Advanced Normalization Tools\u003csup\u003e45\u003c/sup\u003e and was registered to a scanner-specific template in MNI space. The scanner-specific template was created from 30 healthy subjects, 15 individuals with left hippocampal sclerosis and 15 people with right hippocampal sclerosis, using high-resolution whole-brain EPI.\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eShort- and long-term functional imaging time-series were realigned to the mean image and time-corrected using Statistical Parametric Mapping 12 (SPM12; \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.fil.ion.ucl.ac.uk/spm/\u003c/span\u003e\u003cspan address=\"http://www.fil.ion.ucl.ac.uk/spm/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). Normalisation into standard anatomical space was done using EasyReg,\u003csup\u003e46\u003c/sup\u003e a deep-leaning registration method accessible via Freesurfer.\u003csup\u003e47\u003c/sup\u003e Transformation parameters from the T1-to-template registration were used to warp fMRI time-series to template using nearest-neighbour interpolation. Normalized time-series were smoothed on SPM12 using 8mm full-width at half-maximum Gaussian kernel.\u003csup\u003e42\u003c/sup\u003e\u003c/p\u003e \u003cdiv id=\"Sec38\" class=\"Section4\"\u003e \u003ch2\u003eLongitudinal connectivity analysis\u003c/h2\u003e \u003cp\u003e \u003cb\u003eEvent-related contrasts\u003c/b\u003e \u003c/p\u003e \u003cp\u003eEvent-related spmT maps of subsequent memory effects were generated for each subject and separately for words or faces on SPM12 via random-effects analysis of a blocked design general linear model (GLM).\u003csup\u003e5\u003c/sup\u003e Six regressors of interest were created; words and faces subsequently remembered, familiar, or forgotten. Six motion parameters were added as confounds. Resulting event-related statistical maps were used for subsequent single-level connectivity analyses.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec39\" class=\"Section3\"\u003e \u003ch2\u003eMTL seeds\u003c/h2\u003e \u003cp\u003eTo ensure unbiased ROI selection for group comparisons, seed selection was based on AAL-based anatomical masks (WFU-PickAtlas toolbox v3.0). Healthy controls had the left and right hippocampi as MTL seeds, based on their role in successful memory.\u003csup\u003e3,17\u003c/sup\u003e For patients, one MTL seed included the non-resected contralesional hippocampus. Ipsilesionally, the remnant MTL seed entailed remnant hippocampus and parahippocampal gyrus, based on left and right ATLR group resection masks\u003csup\u003e39,48\u003c/sup\u003e. All participants underwent standard ATLR with little within-group difference in the size of resection cavity.\u003c/p\u003e \u003cp\u003e \u003cb\u003eGeneralized PPI analysis\u003c/b\u003e \u003c/p\u003e \u003cp\u003eA generalized form of PPI (gPPI) spanned the entire experimental space,\u003csup\u003e35\u003c/sup\u003e modelling beta-estimates of all subsequent memory conditions (further details in \u003cem\u003esupplementary material\u003c/em\u003e).\u003c/p\u003e \u003cp\u003eAt the participant-level, seed-to-whole-brain connectivity analysis was conducted on MATLAB.\u003csup\u003e35\u003c/sup\u003e For verbal and visual memory separately, the subject-level gPPI model included three regressors: time-course of each event-related task-condition, timeseries of one MTL seed, and of the PPI term (task*seed interaction). All six task-conditions were modelled to better probe successful verbal and visual memory effect.\u003csup\u003e35\u003c/sup\u003e The average seed time-course was extracted within each anatomical MTL mask/seed. Physiological and psychological variables were treated as nuisance regressors. \u003cem\u003eT\u003c/em\u003e-contrasts were generated for each MTL seed and words/faces subsequently remembered, revealing whole-brain cortical areas significantly more correlated with the seed during successful memory encoding than during uncertain/failed conditions, based on the PPI term prediction\u003csup\u003e35\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eFor each participant, separate GLMs were performed for each MTL seed. The same task and seed regressors were used for all participants and at 3\u0026ndash;12-month and 10-year follow-ups. Resulting single-level gPPI \u003cem\u003et\u003c/em\u003e-contrasts of successful subsequent memory were used for group-level random-effects analyses (see below section).\u003c/p\u003e \u003cp\u003e \u003cb\u003eStatistical analyses\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eClinical and neuropsychological data\u003c/b\u003e \u003c/p\u003e \u003cp\u003eData was analysed using R 4.0.5. Demographics were evaluated using Fisher\u0026rsquo;s exact test for sex proportion, one-way ANOVA for parametric z-scores (memory and IQ), and Kruskal\u0026ndash;Wallis tests for nonparametric continuous variables (age, ILAE outcomes, ASM intake and change).\u003csup\u003e42\u003c/sup\u003e For multiple comparisons, post-hoc tests were corrected using Tukey's HSD adjustment.\u003c/p\u003e \u003cp\u003e \u003cb\u003eLongitudinal assessment of the functional memory network\u003c/b\u003e \u003c/p\u003e \u003cp\u003eAll data was analysed with SPM12.\u003c/p\u003e \u003cp\u003e \u003cb\u003eLong-term changes in functional connectivity from 3\u0026ndash;12-month to 10-year follow-ups\u003c/b\u003e \u003c/p\u003e \u003cp\u003eMixed ANOVAs, using flexible factorial design with IQ as confound regressor, were performed to investigate changes in MTL-seeded memory connectivity between short-term and long-term follow-ups in the individual patient groups compared to changes in test-retest over that timeline in healthy subjects. A distinct analysis was conducted for faces and words successfully remembered, seeding from each MTL separately.\u003c/p\u003e \u003cp\u003eFor each subject, the relevant first-level gPPI \u003cem\u003et\u003c/em\u003e-contrasts for each of the scanning timepoint (3\u0026ndash;12 months and 10 years) were entered. Each flexible factorial design involved a random subject factor, a three-levels group factor (controls, left and right ATLR), and a two-levels condition factor (short-term and long-term postoperative scans), allowing the investigation of a Group x Condition interaction for the successful memory contrasts. Differences in activations across scanning sessions were compared between ATLR groups and controls in \u003cem\u003et\u003c/em\u003e-contrasts: 10-year connectivity\u0026thinsp;\u0026gt;\u0026thinsp;3\u0026ndash;12-month connectivity in left or right ATLR versus controls, and 10-year connectivity\u0026thinsp;\u0026lt;\u0026thinsp;3\u0026ndash;12-month connectivity in left or right ATLR versus controls.\u003c/p\u003e \u003cp\u003eIn summary, flexible factorial \u003cem\u003et\u003c/em\u003e-contrasts modelled in each ATLR group, the within-subject differences in MTL-seeded, whole-brain functional connectivity across postoperative follow-ups, beyond the connectivity changes seen in controls.\u003c/p\u003e \u003cp\u003e \u003cb\u003eCorrelation between functional reorganization in TLE and memory recovery\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThree-way ANCOVAs were conducted for each MTL seed and each successful memory contrast (words/faces), to investigate which differences in functional connectivity from 3\u0026ndash;12-month and 10-year follow-ups were related with improvement in memory functions over this timeline. Positive correlations were examined using BMIPB (I or II) verbal and visual learning scores converted into age-normalized z-scores. Difference in z-scores between 3\u0026ndash;12-month and 10-year follow-ups was used as continuous variables in three-ways ANCOVAs.\u003c/p\u003e \u003cp\u003e \u003cb\u003eStatistical thresholds\u003c/b\u003e \u003c/p\u003e \u003cp\u003eGiven our \u003cem\u003ea priori\u003c/em\u003e hypothesis of increased local MTL connectivity (including the fusiform gyrus),\u003csup\u003e5,9,17\u003c/sup\u003e MTL connectivity was corrected for multiple comparisons at \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 voxel-wise, controlling for family-wise error rate via small volume correction.\u003csup\u003e5,32,49\u003c/sup\u003e This included a 6 mm-radius sphere in contralesional MTL regions,\u003csup\u003e3,12\u003c/sup\u003e and 3 mm-radius sphere in remnant hippocampus and parahippocampal gyrus to avoid resection cavity-related activation. All reported seed-to-remnant hippocampus/parahippocampus connectivity was validated against artifacts using exclusive MTL group-resection masks.\u003c/p\u003e \u003cp\u003eGroup comparison and correlation analyses generated highly specific MTL-to-whole-brain, longitudinal, event-related \u003cem\u003et\u003c/em\u003e-contrasts.\u003csup\u003e50\u003c/sup\u003e Thus, at the extra-MTL level, functional connectivity is reported at an exploratory \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001 threshold (uncorrected), alike previous longitudinal, event-related and network fMRI studies.\u003csup\u003e5,12,49\u003c/sup\u003e\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eATLR = anterior temporal lobe resection; ASM = anti-seizure medication; ILAE = International League Against Epilepsy; EPI = echo-planar imaging; F = females; fMRI = functional MRI; fusiform = fusiform gyrus; FWE = family-wise error; G = gyrus; IQ = intelligence quotient; IQR = interquartile range; Inf = inferior; Hippoc. = hippocampus; LGN = lateral geniculate nucleus; M = males; Mid = middle; MTL = medial temporal lobe; N = number; NA = not applicable; NHNN = National Hospital for Neurology and Neurosurgery; Occ= occipital; OFC = orbitofrontal cortex; Operc = operculum; PIQ = performance IQ; Post = Posterior; RCI = reliable change index; Sup = superior; TLE = Temporal Lobe Epilepsy; VIQ = verbal IQ.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAnonymized data for replication of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe would like to thank Andrea Hill, Epilepsy Society radiographer, for her crucial help in data collection, Jane de Tisi for gathering long-term clinical information, Gerard Hall for methods discussion, Bernardo Pimentel for clinical discussion, and all our participants for their invaluable cooperation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work is supported by National Institute for Health Research UCLH Biomedical Research Centre (grant 229811), The Wellcome Trust (grant 083148), Wellcome Trust Innovation Program (106882/Z/15/Z, 218380/Z/19/Z) and MRC (G0802012, MR/M00841X/1). MF and MKS are supported by the UCLH BRC and the Epilepsy Society.\u0026nbsp;PT is supported by a UKRI Future Leaders Fellowship (MR/T04294X/1). This work and MKS are supported by the MRC (grant MR/X031039/1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNeuroimage data collection: MF, MKS, LPB, GPW, SBuck. Neuropsychology testing: PJT, SBaxendale, and MF. Conception and study design: MKS and MF. Data processing, statistical analysis, and interpretation: MF, MKS. Physics support: LPB and PT. Neuroimage processing support: LPB. Data analysis support: FX and LPB. Data interpretation support: DG, LG, MKJ, JSD and MKS. Manuscript and supporting materials write-up: MF, MKS. Manuscript preparation support: LPB, PT, FX, DG, LG, GPW, MKJ. Project supervision: MKS and JSD. All authors approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors report no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eJobst BC, Cascino GD (2015) Resective epilepsy surgery for drug-resistant focal epilepsy: a review. JAMA 313:285\u0026ndash;293\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSquire LR, Stark CE, Clark RE (2004) The medial temporal lobe. 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JAMA Neurol 76:690\u0026ndash;700\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTrimmel K et al (2018) Left temporal lobe language network connectivity in temporal lobe epilepsy. Brain 141:2406\u0026ndash;2418. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/brain/awy164\u003c/span\u003e\u003cspan address=\"10.1093/brain/awy164\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTelzer EH et al (2018) Methodological considerations for developmental longitudinal fMRI research. Dev Cogn Neurosci 33:149\u0026ndash;160. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.dcn.2018.02.004\u003c/span\u003e\u003cspan address=\"10.1016/j.dcn.2018.02.004\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eDemographics and clinical details of people who had anterior temporal lobe resection and controls.\u003c/div\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eSex\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003eM (F)\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eAge\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003eMedian (IQR)\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eDuration\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003eMedian (IQR)\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eSeizure Frequency\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003eMedian\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e(IQR)\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eILAE Seizure Outcome\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eAnti-Seizure Medications (ASM)\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eT2\u003c/span\u003e\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eT3\u003c/span\u003e\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eT2 to T3\u003c/span\u003e\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eT3\u003c/span\u003e\u003c/div\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLeft ATLR \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003e(n\u0026thinsp;=\u0026thinsp;12)\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e7 (5)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e38 (13)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e12.5 (16)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e6 (0)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eClass 1\u0026ndash;2: 10\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003eClass 4\u0026ndash;5: 2\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eClass 1: 10\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003eClass 3\u0026ndash;5: 2\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLess/off: 6\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003eSame: 4\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003eExtra 1\u0026ndash;2: 2\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eNone: 4\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e1\u0026ndash;2 ASMs: 7\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e3 ASMs: 1\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight ATLR\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003e(n\u0026thinsp;=\u0026thinsp;13)\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e4 (9)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e38 (21)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e16 (21)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e10 (5)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eClass 1: 11\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003eClass 2\u0026ndash;3: 2\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eClass 1: 12\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003eClass 2: 1\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLess/off: 7\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003eSame: 6\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eNone: 6\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e1\u0026ndash;2 ASMs: 6\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e3 ASMs: 1\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eControls\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003e(n\u0026thinsp;=\u0026thinsp;10)\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e4 (5)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e37 (23)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eNA\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eNA\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eNA\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eNA\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eNA\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eNA\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP-value\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003e0.40\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003e0.80\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003e0.37\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003e0.91\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003e0.48\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003e0.44\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003e0.76\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003e0.77\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eStatistical difference between groups is presented, for gender using two-sided Fisher exact p-value, and with Kruskal-Wallis p-values for age, duration, and frequency (all at time of surgery), ILAE outcome and ASM intake. Median (IQR) age and duration at time of surgery are presented in years, while seizure frequency in group median per months. ASM = anti-seizure medications; ATLR= anterior temporal lobe resection; ILAE = International League Against Epilepsy; IQR= interquartile range; F= females; M = males; N = number; NA = not applicable; T2 = 3\u0026ndash;12-month follow-up (median 11 months); T3 = 10-year follow-up (median 9 years).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eNeuropsychometry measures across experimental assessments in healthy controls and in left or right resection groups.\u003c/div\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003ePreoperative IQ\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eVerbal memory z-scores\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eVisual memory z-scores\u003c/div\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eVIQ\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003ePIQ\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eT1\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eT2\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eT3\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eT1\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eT2\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eT3\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eControls\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003e(n\u0026thinsp;=\u0026thinsp;10)\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.44 (0.69)\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eFSIQ\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.22 (0.78)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.13 (0.90)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.55 (1.01)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e-0.43 (0.88)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.71 (0.58)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.83 (0.36)\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLeft ATLR\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003e(n\u0026thinsp;=\u0026thinsp;12)\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e-0.74 (0.60)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e-0.45 (0.49)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e-0.72 (1.33)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e-1.53 (1.55)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e-0.38 (0.87)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.08 (0.84)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.08 (0.84)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.16 (1.04)\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight ATLR \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003e(n\u0026thinsp;=\u0026thinsp;13)\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e-0.70 (0.91)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e-0.45 (0.77)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e-1.51 (1.22)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e-0.84 (1.38)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.71 (0.50)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.71 (0.50)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e-0.77(1.15)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e-0.33(1.35)\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP-value\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e0.001\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e0.004\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e0.006\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e\u0026lt;\u0026thinsp;0.001\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e0.029\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e0.003\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e0.002\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.076\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eIn controls, full scale IQ (FSIQ) is reported, while in patients, premorbid IQ was assessed via the NART-2; verbal and performance IQ subtests evaluate verbal and non-verbal reasoning. Clinically meaningful changes in z-scores are calculated based on the reliable change index (RCI), using a 95% confidence interval. . For verbal memory from 3\u0026ndash;12 months to 10 years, this meant an RCI improvement of \u0026ge; 0.31 and a RCI decline of \u0026ge; 0.40. For visual memory from 3\u0026ndash;12 months to 10 years, an RCI improvement of \u0026ge; 0.58 and RCI decline of \u0026ge; 0.16 were deemed clinically significant. All values are shown as mean (standard deviation). P-values are reported for each one-way ANOVA, and significant \u003cem\u003eP\u003c/em\u003e-values are shown in bold. ATLR = anterior temporal lobe resection; N = number; T2 = 3\u0026ndash;12-month follow-up (median 11 months); T3 = 10-year follow-up (median 9 years); VIQ = verbal IQ; PIQ = performance IQ.\u003c/p\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eFunctional connectivity changes from 3\u0026ndash;12 months to 10 years after anterior temporal lobe resection in people with epilepsy, over and above changes seen in controls.\u003c/div\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eConnectivity\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003eT2 to T3\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLeft ATLR\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight ATLR\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eLeft MTL seed\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eRight MTL seed\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eLeft MTL seed\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eRight MTL seed\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"5\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eWords remembered\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eConnectivity increases\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLeft post fusiform \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003e(occ.)\u003c/span\u003e\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e-34, -84, -14\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.025\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight post parahippocampal G\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e18, -42, -6\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.044\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eNo suprathreshold connectivity\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight post fusiform \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003e(temp-occ.)\u003c/span\u003e\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e36, -42, -16\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.027\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLeft post fusiform \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003e(temp-occ.)\u003c/span\u003e\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e-24 -42, -14\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.042\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight post fusiform \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003e(occ.)\u003c/span\u003e\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e32, -76, -14\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.027\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight post parahippocampal G\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e18, -42, -8\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.040\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight sub callus of ACC\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e10, -28, -8\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eConnectivity decreases\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eNo suprathreshold connectivity\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight thalamus (LGN)\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e18, -28, -4\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eNo suprathreshold connectivity\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eNo suprathreshold connectivity\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"6\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eFaces Remembered\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"5\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eConnectivity increases\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLeft post parahippocampal G\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e-14, -36, -12\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.018\u003csup\u003eb\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight amygdala\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e26, 4, -20\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.027\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLeft post fusiform \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003e(temporal)\u003c/span\u003e\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e-38, -26, -16\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.030\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight post parahippocampal G\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e26, -28, -22\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.042\u003csup\u003eb\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLeft post fusiform \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003e(temp-occ.)\u003c/span\u003e\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e-20, -48, -16\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight sup frontal G\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e18, -10, 60\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight post fusiform \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003e(occ.)\u003c/span\u003e\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e30, -70, -2\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.015\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLeft inf temporal G\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e-46, -38, -14\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight lingual gyrus\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e28, -72, -2\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight post fusiform \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003e(temp-occ.)\u003c/span\u003e\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e36, -60, -14\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.007\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight mid fusiform \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003e(temporal)\u003c/span\u003e\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e34, -40, -16\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.048\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eConnectivity decreases\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eNo suprathreshold connectivity\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eNo suprathreshold connectivity\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLeft insula\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e-36, 4, -12\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eNo suprathreshold connectivity\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eT\u003c/em\u003e-contrasts results of mixed ANOVAs using a flexible factorial design with IQ as confound variable. The changes in functional connectivity across postoperatively follow-ups are presented in patient groups, over and above changes in controls, seeding from the left and right medial temporal lobes (MTL). MTL-to-neocortex connectivity is displayed at \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001, uncorrected.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ea\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05, FWE correction, using a 6mm sphere for contralesional MTL regions.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003eb\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05, FWE correction 3mm sphere in remnant MTL regions to avoid resection cavity-related activations.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eACC= anterior cingulate cortex; ATLR= anterior temporal lobe resection; Fusiform = fusiform gyrus; FWE = Family Wise Error; G = gyrus; Inf = inferior; LGN= lateral geniculate nucleus; Mid = middle; MTL = medial temporal lobe; Post = posterior; Occ= occipital; Sup = superior; T2 = 3\u0026ndash;12-month follow-up (median 11 months); T3 = 10-year follow-up (median 9 years).\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eCorrelations between long-term verbal memory improvement and longitudinal changes in task-based functional connectivity from 3\u0026ndash;12 months to 10 years after anterior temporal lobe resection.\u003c/div\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" style=\"width: 11.589%;\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\" style=\"width: 39.4254%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLeft resection group\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\" style=\"width: 15.7702%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight resection group\u003c/div\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 11.589%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.7929%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eLeft MTL seed\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.7929%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eRight MTL seed\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 16.0201%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eLeft MTL seed\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.6116%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eRight MTL seed\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"3\" style=\"width: 11.589%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eConnectivity increases\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003eT2 to T3\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.7929%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLeft post fusiform gyrus\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e-34 -84 -14\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.019\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.7929%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight post parahippocampal gyrus\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e18\u0026ndash;42 -6\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.036\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 16.0201%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight post parahippocampal gyrus\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e36\u0026ndash;46 -6\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.049\u003csup\u003eb\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.6116%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight post fusiform gyrus\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e36\u0026ndash;42 -16\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.012\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 15.7929%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLeft post fusiform gyrus\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e-26 -44 -12\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.042\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.7929%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 16.0201%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.6116%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight post fusiform gyrus\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e44\u0026thinsp;\u0026minus;\u0026thinsp;42 -22\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.020\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 15.7929%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight post parahippocampal gyrus\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e18\u0026ndash;42 -8\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.034\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.7929%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 16.0201%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.6116%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight post fusiform gyrus\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e32\u0026ndash;76 -14\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.022\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\" style=\"width: 11.589%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eConnectivity decreases\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003eT2 to T3\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.7929%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLeft inf parietal gyrus\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e-50 -28 44\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.7929%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight thalamus\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e18\u0026ndash;28 -4\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 16.0201%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLeft sup temporal gyrus\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e-50 -44 20\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.6116%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight thalamus\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e18\u0026ndash;28 -4\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 15.7929%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.7929%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight supramarginal gyrus\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e66\u0026thinsp;\u0026minus;\u0026thinsp;36 24\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 16.0201%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 12.6116%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight supramarginal gyrus\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e66\u0026thinsp;\u0026minus;\u0026thinsp;30 26\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003eResults of three-way ANCOVAs for each MTL seed during encoding of words subsequently remembered. These are the functional connectivity changes from short- to long-term follow-ups in patients that were significantly correlated with improvement in verbal memory z-scores (i.e., from list-learning test) over that timeline. These were analysed relative to connectivity changes and memory of healthy controls. MTL seed to extra-MTL connectivity is displayed at \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001, uncorrected.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ea\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05, FWE correction, using a 6mm sphere for contralesional MTL regions.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003eb\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05, FWE correction 3mm sphere in remnant MTL regions.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFWE = family-wise error; G = gyrus; Inf = inferior; Mid = middle; MTL = medial temporal lobe; Post = Posterior; Sup = superior; T2 = 3\u0026ndash;12-month follow-up (median 11 months); T3 = 10-year follow-up (median 9 years).\u003c/p\u003e\n\u003ctable id=\"Tab5\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eCorrelations between long-term visual memory improvement and longitudinal changes in task-based functional connectivity from 3\u0026ndash;12 months to 10 years after anterior temporal lobe resection.\u003c/div\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLeft resection group\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight resection group\u003c/div\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eLeft MTL seed\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eRight MTL seed\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eLeft MTL seed\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eRight MTL seed\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"7\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eConnectivity increases\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003eT2 to T3\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLeft post fusiform G\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e-18 -48 -14\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLeft post hippocampus\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e-22 -36 -2\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.030\u003csup\u003eb\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLeft post fusiform G\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e-38 -26 -18\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.014\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLeft post fusiform G\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e-20 -86 -6\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.046\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLeft post fusiform G\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e-34 -64 -10\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.004\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLeft mid temporal G\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e-50 -18 -16\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight post fusiform G\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e36\u0026ndash;64 -14\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.015\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLeft post fusiform G\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e-40 -56 -10\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.048\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight post fusiform G\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e36\u0026ndash;62 -14\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight posterior OFC\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e28 34\u0026thinsp;\u0026minus;\u0026thinsp;18\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight post fusiform G\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e36\u0026ndash;40 -14\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.019\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLeft inf temporal G\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e-44 -54 -4\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLeft inf temporal G\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e-44 -36 -14\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight sup frontal G\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e18\u0026thinsp;\u0026minus;\u0026thinsp;10 60\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight mid temporal G\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e40\u0026ndash;58 16\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLeft medial OFC\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e-16 36\u0026thinsp;\u0026minus;\u0026thinsp;16\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight lingual G\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e24\u0026ndash;72 -4\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLeft insula\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e-30 18\u0026ndash;20\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRight mid temporal G\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e40\u0026ndash;56 -16\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eConnectivity decreases\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003eT2 to T3\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eNo suprathreshold connectivity\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eNo suprathreshold connectivity\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eNo suprathreshold connectivity\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eNo suprathreshold connectivity\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003eResults of three-way ANCOVAs for each MTL seed during encoding of faces subsequently remembered. These represent longitudinal connectivity changes in patients that were significantly correlated with improvement in visual memory z-scores (i.e., from design learning test) from short to long-term post-surgery. These analyses were performed relative to connectivity changes and memory of healthy controls. MTL-to-neocortex connectivity is displayed at \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001, uncorrected.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ea\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05, FWE correction, using a 6mm sphere for contralesional MTL regions.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003eb\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05, FWE correction 3mm sphere in remnant MTL regions. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFWE = family-wise error; G = gyrus; Inf = inferior; Mid = middle; MTL = medial temporal lobe; OFC = orbitofrontal cortex; Post = Posterior; Sup = superior; T2 = 3\u0026ndash;12-month follow-up (median 11 months); T3 = 10-year follow-up (median 9 years).\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"neuroplasticity, episodic memory, functional connectivity, anterior temporal lobe resection, fMRI","lastPublishedDoi":"10.21203/rs.3.rs-3936758/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3936758/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eApproximately 40% of individuals undergoing anterior temporal lobe resection for temporal lobe epilepsy experience episodic memory decline. Despite the importance of early memory network changes, long-term plasticity and its impact on memory function are unclear. Our study investigates neural mechanisms of memory recovery and network plasticity over nearly a decade post-surgery.\u003c/p\u003e \u003cp\u003eFrom 3\u0026ndash;12 months to 10 years postoperatively, we assessed memory network changes in 25 patients (12 left-sided resections) relative to 10 healthy matched controls, using longitudinal, task-based functional MRI and standard neuropsychology assessments.\u003c/p\u003e \u003cp\u003eIn a predominantly seizure-free cohort, our findings highlight the potential for sustained cognitive improvement and reduced medication needs over a decade after epilepsy surgery. We observed specific changes in memory networks and identified regions crucial for long-term verbal and visual memory recovery.\u003c/p\u003e \u003cp\u003eThese findings endorse strategic approaches in epilepsy treatment: advocating for conservative surgeries and promoting the long-term use of cognitive rehabilitation for ongoing recovery.\u003c/p\u003e","manuscriptTitle":"Long-Term Memory Plasticity: A Decade-Long Connectivity Study Post Anterior Temporal Lobe Resection","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-20 17:52:20","doi":"10.21203/rs.3.rs-3936758/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-communications","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"NCOMMS","sideBox":"Learn more about [Nature Communications](http://www.nature.com/ncomms/)","snPcode":"","submissionUrl":"https://mts-ncomms.nature.com/","title":"Nature Communications","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Communications","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"3f8c3be9-70ee-40bd-8341-33ec6fe2788c","owner":[],"postedDate":"February 20th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":28801320,"name":"Biological sciences/Neuroscience/Diseases of the nervous system/Epilepsy"},{"id":28801321,"name":"Biological sciences/Neuroscience/Cognitive neuroscience"}],"tags":[],"updatedAt":"2025-01-16T08:06:43+00:00","versionOfRecord":{"articleIdentity":"rs-3936758","link":"https://doi.org/10.1038/s41467-024-55704-x","journal":{"identity":"nature-communications","isVorOnly":false,"title":"Nature Communications"},"publishedOn":"2025-01-15 05:00:00","publishedOnDateReadable":"January 15th, 2025"},"versionCreatedAt":"2024-02-20 17:52:20","video":"","vorDoi":"10.1038/s41467-024-55704-x","vorDoiUrl":"https://doi.org/10.1038/s41467-024-55704-x","workflowStages":[]},"version":"v1","identity":"rs-3936758","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3936758","identity":"rs-3936758","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}