Effect and mechanism of lateralization of cerebellar-cerebellar network abnormalities on language in patients with unilateral temporal lobe epilepsy

Effect and mechanism of lateralization of cerebellar-cerebellar network abnormalities on language in patients with unilateral temporal lobe epilepsy | 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 Research Article Effect and mechanism of lateralization of cerebellar-cerebellar network abnormalities on language in patients with unilateral temporal lobe epilepsy Linlin Pang, Zirong Chen, Binglin Fan, Zexiang Chen, Xiaomin Pang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5397184/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective Since epilepsy is associated with different levels of cerebral dysfunction, there may be a recombination of language circuits in the course of epilepsy. The cerebellum is part of the whole brain language network. We explored the differences in speech impairment patterns in patients with TLE and different hemiencephalic attacks from the perspective of the cerebellum. Methods Fifty-eight patients with TLE and 30 healthy controls were recruited. including 28 patients with left temporal lobe epilepsy (LTLE) and 30 patients with right temporal lobe epilepsy (RTLE). The resting state functional connection method was used to investigate the effects of lateralization and cerebellar laterality on language function in patients with TLE. The differences in functional connectivity (FC) in the whole cerebellar cortex were compared between the three groups. Results The FC analysis of the LTLE, RTLE, and HC groups showed significant differences between the three groups. Compared with the HC group, FC was decreased from the Cerebelum_Crus2_R to the right frontal cortex, from the Cerebelum_7_L to the right frontal cortex in both LTLE and RTLE groups. Compared with the LTLE group, FC was decreased from the Cerebelum_3_R to the left frontal pole, left inferior frontal gyrus, and left frontoorbital cortex in the RTLE group. Compared with the HC group, FC in the RTLE group was decreased between the Cerebelum 9L and right medial superior frontal gyrus and right dorsolateral superior frontal gyrus; between Cerebelum 9R and right medial superior frontal gyrus and left dorsolateral superior frontal gyrus; between Vermis9 and left posterior parietal lobe, between Vermis10 and right angular gyrus; between left middle temporal gyrus and language network; between right middle temporal gyrus and language network. Conclusion In the brain regions related to language, patients with RTLE had stronger left hemispheric activation than patients with LTLE. At the node level, the RTLE group had greater language central connection disorder than the HC group. Cerebellar-cerebral FC has different connectivity patterns between LTLE and RTLE groups. Cerebellar injury of TLE may lead to functional reorganization and transfer of language dominance to homologous regions in the other hemisphere. Temporal lobe epilepsy Cerebellum Language impairment Functional connectivity Resting-state functional magnetic resonance imaging Figures Figure 1 Figure 2 Figure 3 1 Introduction In most cases, language ability manifests in two well-defined regions of the left hemisphere : Broca's area in the inferior frontal gyrus and Wernicke's area in the superior temporal gyrus [1] . However, there is a higher proportion of atypical verbal presentations in patients with epilepsy. This may include abnormal presentations of the language dominant hemisphere or atypical lateralization [2] . Although the role of the left hemisphere in understanding language is well established, a growing number of scholars support the idea that the right hemisphere has a similar role in word-semantic processing [3, 4] . Studies have shown that damage to both the left hemisphere (LH) and right hemisphere (RH) of the brain impairs the resolution of ambiguous words in context. Moreover, the deficiencies in both groups focus on difficulties in using contextual information. Left hemisphere’s impairment can impair the initial ability to integrate semanteme into context, while also producing a faster-than-normal decline in word activation. Damage to the right hemisphere can also impair the initial acquisition of contextual information and lead to a reliance on frequency-based lexical activation. Both hemispheres need access to contextual information to successfully accomplish ambiguity resolution. The two hemispheres work together and play an important role in the process of resolution [5] . The distance between the language area and the epileptic focus in patients with TLE indicates that cerebral dysfunction occurs in a region outside the epileptic area without structural abnormalities. In fact, metabolic disorders have been observed in the temporal and frontal regions beyond the damaged temporal lobe [6] . Since lateralization of speech in epileptic patients is associated with different levels of cerebral dysfunction, there may be a recombination of language circuits in the course of epilepsy, and the recombination of language circuits to the right hemisphere may represent an adaptive process [7] . Neudorf et al. found that patients with RTLE exhibit stronger LH activation in language-related brain regions (tegmentum and fusiform gyrus) than patients with LTLE and HCs [8] . Zimmermann et al. [9] assessed the use of language fluency in 40 adults with vascular injury in the right hemisphere. The results showed that the patient group showed a greater degree of impairment in semantic fluency tasks. These studies show that there are differences in language lateralization between patients with LTLE and RTLE. Combined with changes in cerebellar activity during seizures, Martha et al. suggested that the cerebellum may be a potential therapeutic target for controlling epilepsy [10, 11] . Different regions of the cerebellar cortex are involved in motor, language, working memory, social and emotional tasks. Non-motor processing mainly occurs in lobule VI, Crus I/II, VIIB, IX, and X [12] . Both the cerebral hemispheres and the cerebellum are activated when performing specific language tasks. A stronger laterality of language to the cerebral hemisphere predicts a stronger laterality to the contralateral cerebellar hemisphere. In almost all cases of lateralization of cerebellar activation, there is a crossed cerebellar-cerebellar lateralization pattern regardless of whether the language presentation is typical or atypical. According to previous studies, when the cerebellum is obviously lateralized, the language laterality of the brain can be considered contralateral [13] . We speculate that in patients with TLE and language disorders, the cerebellum is involved during repeated attacks, which may damage the cerebellar language functional network of TLE patients, and lead to differences in cerebellar language functional networks of patients with different literalitiess of TLE. This difference in cerebellar functional brain networks can be used as an additional diagnostic feature to determine hemispheric language advantage in patients with lateralized TLE. Here, we considered the cerebellum as the area of interest to construct cerebellar-brain functional connectivity networks and explore the differences in speech impairment patterns in patients with TLE and different hemiencephalic episodes. 2 Materials and methods 2.1 Participants Our study was approved by the Ethical Committee of the First Affliated Hospital of Guangxi Medical University, Written informed consent was obtained from each participant. Fifty-eight patients with TLE in the epilepsy clinic of Department of Neurology of Guangxi Medical University were recruited from 2019 to 2022, including 28 participants in the LTLE group and 30 participants in the RTLE group. All patients with TLE epilepsy were diagnosed by two experienced epilepsy experts according to the diagnostic criteria of the International Anti-Epilepsy Alliance Association. The inclusion criteria for patients with TLE were as follows: (1) age between 18 and 50 years old, and scalp EEG showed epileptic discharge from unilateral temporal lobe during attack or intermission; (2) clinical symptoms of seizure were consistent with temporal lobe seizure and participants understood and signed the experimental informed consent form; (3) regular use of antiepileptic drugs, with no obvious mental illnesses or other serious systemic diseases. (4) except for hippocampal sclerosis, no structural abnormality was found in MRI. The exclusion criteria for patients with TLE were as follows: (1) other systemic, neurological, and mental disorders; (2) diagnosis of multifocal or extratemporal epilepsy; (3) developmental defects, cortical malformations, or other focal lesions in MRI; (4) severe mental disorders or dementia; (5) not cooperating during the examination; (6) any history of drug or alcohol abuse. The study included 30 healthy adult participants whose age, sex, and education matched those of patients with TLE. All participants were right-handed and signed written informed consent. This study was approved by the Medical Ethics Committee of Clinical Research of Guangxi Medical University. The normal control group included healthy volunteers whose sex, age and education level matched with those of TLE patients. They were right-handed, with no history of alcohol drinking, drug addiction or dependence, brain trauma or other neuropsychiatric disorders. 2.2 Language testing Using the Boston naming test (BNT) due to Chinese culture, 30 items were selected from the 60 original items. For each one of the 30 items, the Chinese name of the object was set as the target response, and a semantic prompt is designed for each response, just like the original version of BNT. The presentation order of the three options for each project (target response, semantic interference, and perceptual interference) was random. The measure of naming performance included the total number of correct items after spontaneous naming, semantic prompt, and multiple selection recognition. If the participant named the project correctly, the assessor continued to test the next project. If the participant wrongly responded, or did not respond within 20 seconds, then a semantic clue was given. If the subject could not correctly say the name of the object after providing the semantic clue, he did not receive a score [14] . Verbal fluency test (VFT) is used to measure the spontaneous generation of a certain class of words in a limited time. The Chinese version of VFT was used in this study. The controlled oral vocabulary association test, especially the "fruit" category test, was used to assess semantic fluency. The subjects were asked to say as many different fruit names as possible in 1 minute. The test emphasizes the speed of generating the target word as soon as possible, rather than the quality of the answer. The examiner told tell the subject “this is a test to see how quickly you can say words that begin with a particular category.” The quality of speech is not important." VFT instructions include the types of errors to avoid (e.g., proper nouns) and also include error samples to ensure participants fully understand all rules. Temporal changes are not encouraged, and the purpose of these improvements is to ensure that each participant clearly understands that this is a 1-minute speed performance task and which types of responses are acceptable. Before the first test, a sample test of three to four words was conducted to ensure that each participant understood the task and, rebooted if necessary. We also asked participants if they had any questions [15, 16] . 2.3 Resting fMRI data acquisition Magnetic resonance imaging data w ere collected using an Achievia3.0T magnetic resonance imaging scanner (Philips, Amsterdam, the Netherlands). The 12-channel head phased array surface coil was used for data acquisition. The rs-fMRI scan lasted for 450s and 225 time points were obtained. During the scan, participants were reminded to close their eyes, stay awake and not think about anything. We used headphones and cushions to reduce noise and restrict head movement. We acquired sagittal high-resolution T1-weighted images. The axial T2 fluid-attenuated inversion recovery sequence was then used to remove clinically asymptomatic encephalopathy. The following parameters were adopted for RS-fMRI: repetition time (TR) / echo time (TE) = 2000 ms, voxel size = 3.44 mm × 3.44 mm × 4 mm, field of view = 220 mm × 220 mm, matrix size = 64 × 64, flip angle = 90°, number of slices = 41, slice thickness = 3.5 mm. slice gap = 0.5 mm. The parameters used for high-resolution 3DT1W weighted structural image were as follows: TR/TE = 7.8/ 3.4 ms, flip angle = 9°, field of view = 256 mm × 256 mm, image matrix = 256 × 256, number of slices = 176 slices, slice thickness = 1 mm, voxel size = 1.0 mm × 1.0 mm × 1.0 mm. 2.4 Analysis of resting fMRI data 2.4.1 MRI data preprocessing Based on the MATLAB R2018b running "CONN19c toolbox", we chose seed-based technology. We selected the default parameters to preprocess and analyze data. Preprocessing includeds the following steps: noise source reduction, first-level individual analysis (including correlation analysis), and second-level random effect group analysis, including time layer correction, system odd correction, head motion correction, image registration, image segmentation, spatial standardization, spatial smoothing (FWHM = 6mm), and 3D structure T1 weighted co-registration. 2.4.2 Functional connectivity analysis of resting state fMRI The CONN toolbox provides 116 ROIs comprising the cortical and subcortical regions of the AAL template and cerebellar regions. Therefore, 26 cerebellar regions were selected as ROIs. The indexes, names, and MNI coordinates of the 26 cerebellar ROIs used in this study are shown in the supplementary tabl e1 . The gray matter, white matter, and cerebrospinal fluid were separated from the image. We conducted noise reduction, primary individual analysis (including correlation analysis) and secondary random effect group analysis. The functional connectivity of network recognition based on ROI correlation analysis mainly focuses on sensorimotor network, language network, visual network, highlight network and default mode network. After selecting the bilateral cerebellum as the ROI, the whole brain could be associated with the time process, thus generating a spatial map of the network of interest. The cerebellar-whole brain functional connection, the correlation maps of the whole brain voxel ROI and ROI were calculated to show the cerebellar-whole brain functional connection. Unwanted head movements, physiological effects, and other noises were removed by linear regression and bandpass filtering. The general linear model weighted regression and correlation measurement were conducted, and the Fisher R to Z transform was used to generate the z graph for each subject. Finally, age, sex, and education level were used as covariates to analyze differences in functional connectivity between the two groups (P < 0.05, FDR correction). 2.5 Statistical analysis Statistical analysis was conducted using SPSS23.0 software. Demographic, clinical and neuropsychological data were analyzed. Independent sample T test was used to analyze the difference between normal distribution and uniform variance between the two groups. Mann-Whitney test was used for data with no normal distribution or uneven variance. Chi-square test was used for qualitative variables. p < 0.05 was considered statistically significant. 3 Result 3.1 Demographic, clinical, and behavioral data Table 1 shows the demographic data and clinical characteristics of 28 patients with LTLE, 30 patients with RTLE, and 30 HC group. There was no statistically significant difference in age, sex, and education level. The BNT and VFT scores of patients with LTLE and RTLE were significantly lower than those of normal controls, but there was no difference between the LTLE group and the RTLE group. Table 1 Demographics, clinical and language scale scores of subjects in three groups Variables LTLE(n = 28) RTLE(n = 30) HC(n = 30) P Demographic characteristics Age (years) 30.79 ± 8.03 30.67 ± 9.60 27.23 ± 5.76 0.155 a Sex (male/female) 8/20 11/19 10/20 0.806 b Education (years) Clinical features Age at onset (years) Epilepsy duration (years) Seizure type (Focal/FBTCS) AEDs (mono-/polytherapy) 13.50(9–15) 19.07 ± 9.20 8.00(5.00-16.25) 15/13 10/18 12.00(9–15) 20.10 ± 11.11 9.50(5.00–15.00) 21/9 12/18 12.00(9–16) NA NA NA NA 0.938 e 0.704d 0.981c NA NA Neuropsychological test BNT VFT 25(22.25–27.75) 10.32 ± 3.80 24.00(20.00–27.00) 10.37 ± 3.98 29(27.75-30) 15.63 ± 3.35 0.000e* 0.000a* Data are expressed as mean ± standard deviation and median (upper and lower quartile). a: one-way ANOVA was used to compare groups; b: χ 2 test was used to measure the significance level; c: Mann-Whitney test was used to measure the significance level; d: independent sample t test was used to measure the significance level; e: Kruskal-Wallis test was used. There was a significant difference (P < 0.05). *. Post-mortem analysis showed that there were significant differences between patients with LTLE and RTLE and HCs. LTLE: left temporal lobe epilepsy; RTLE: right temporal lobe epilepsy; HC: healthy control; FBTCS: focal to bilateral tonic-clonic seizures; FD: frame-wise displacement; AEDs: antiepileptic drugs; NA, unavailable; BNT: Boston naming test; VFT: verbal fluency test. 3.2 Functional connectivity analysis 3.2.1 Seed- to-Voxel result We set the seed point to the bilateral cerebellar region for functional connectivity analysis. The functional connections of Cerebelum_3_R, Cerebelum_7_L, and Cerebelum_Crus 2_R were significantly different between the three groups (Fig. 1 and Table 2 ). When Cerebelum_Crus2_R was used as ROI, the right frontal functional connection of patients with LTLE and RTLE was lower than that of the HC group. There was no difference between the RTLE and LTLE groups (Fig. 2 A and B). When Cerebelum_7_L was used as ROI, the right frontal functional connection of LTLE and RTLE patients was lower than that of the HC group, but there was no difference between the RTLE and LTLE groups (Fig. 2 C, D). When Cerebelum_3_R was used as ROI, the functional connections of left frontal pole, left inferior frontal gyrus and left fronto-orbital cortex in the RTLE group were lower than those in the LTLE group (Fig. 2 E). Table 3 shows the details of the brain regions with abnormal FC intensity. The above results show language lateralization in the cerebrum and cerebellum of patients with TLE. When Cerebelum_3_R and Cerebelum_7_L were used as seeds, cross cerebrocerebellar activation was found in both RTLE and LTLE patients. When Cerebelum_Crus2_R was used as the seed, patients showed language lateralization to the same side in the cerebellum and cerebral cortex. Table 2 Differences in resting state FC among the three groups (GroupANOVA) Seed Region Cluster Coordinates Cluster Size Cluster Regions Cluster p-Value(FDR) Cerebelum_3_R -48 + 44 − 04 352 72 Frontal Pole Left Inferior Frontal Gyrus Left 0.000029 Cerebelum_7_L + 20 + 62 − 16 206 Frontal Pole Right 0.014566 Cerebelum_Crus2_R + 14 + 62 + 04 181 Frontal Pole Right 0.015814 Results were corrected by FDR, P < 0.05. There were significant differences (excluding gender, age, education and cephalomotor factors). ANOVA: analysis of variance Table 3 Differences in resting state FC among the three groups(Post hoc t-test) Seed Region Group Cluster Coordinates Cluster Size Cluster Regions Cluster p-Value(FDR) Cerebelum_3_R LTLE vs RTLE -48 + 44 − 14 416 94 73 Frontal Pole Left Inferior Frontal Gyrus Left Frontal Orbital Cortex Left 0.000010 LTLE vs HC n.s. n.s. n.s. n.s. RTLE vs HC n.s. n.s. n.s. n.s. Cerebelum_7_L LTLE vs RTLE n.s. n.s. n.s. n.s. LTLE vs HC + 24 + 62 − 12 176 Frontal Pole Right 0.034397 RTLE vs HC + 20 + 60 − 16 198 Frontal Pole Right 0.017768 Cerebelum_Crus2_R LTLE vs RTLE n.s. n.s. n.s. n.s. LTLE vs HC + 14 + 62 + 02 170 Frontal Pole Right 0.021973 RTLE vs HC + 16 + 36 + 44 191 Frontal Pole Right 0.047409 Results were corrected by FDR, P < 0.05. There were significant differences (excluding gender, age, education and cephalomotor factors). n.s.: no significance was found. 3.2.1 ROI-to-ROI result The connection map between the RTLE group and the HC group revealed significant differences in functional connections between the two brain regions (Fig. 3 ). Specifically, it shows a Chord diagram of the ROI-to-ROI analysis after FDR correction for P-values. Compared with the HC group, the connections that significantly decreased the FC of language-related brain network nodes in the RTLE group were mainly between Cerebelum9L and Frontal Sup MedR, Frontal Sup R; between Cerebelum9R, right medial superior frontal gyrus, and left dorsolateral superior frontal gyrus (Frontal Sup L); between Vermis 9 and FrontoParietal.PPC L); between Vermis10 and Angular R; between Temporal Pol Mid L and Language.Pstg r; between Temporal Pol Mid R and Language.Pstg l/r. The language network consisted of bilateral inferior frontal gyrus (IFG) and bilateral superior temporal gyrus (STG), which were selected from the default automatic templates provided in the Conn toolbox. In terms of functional connections, no significant differences were found between the LTLE and RTLE groups or between LTLE and HC groups. 4 Discussion In this study, the functional cerebrocerebellar connections related to language in patients with LTLE and RTLE were analyzed at the baseline level of the resting brain. We found abnormalities in the functional connections between the cerebellum and the language network. Functional magnetic resonance imaging (fMRI) is a feasible neuroimaging tool for diagnosing hemispheric language dominance. Spontaneous neural activity in the resting state can also be considered the baseline activity of the brain. Comparing blood oxygen concentration- dependent (BOLD) levels between different parts of the brain shows a certain regulatory system and organization. There are also some similarities in this activation mode, known as brain network activity in the resting state. It is correctly verified by cortical electrical stimulation [13] . Outside the traditional "Wernicke area", there is a language area in the temporoparietal of the left hemisphere, namely the middle temporal gyrus, inferior temporal gyrus, fusiform gyrus and angular gyrus. Outside the classic "Broca area", the left prefrontal lobe has a wide range of language areas [17] . In individuals with left-hemisphere language dominance, this task has been shown to activate the right cerebellum. Petra et al. indicated the patterns of cerebellar cross language lateralization in healthy individuals, including typical left-sided language lateralization and atypical right-sided language lateralization [18] . Atypical language may manifest as a transfer of language function to the contralateral hemisphere or to the ipsilateral language area, or both. This cerebellar crossover language lateralization may be a useful diagnostic feature for determining language hemispheric dominance in patients with TLE, as cerebro-cerebellar language activation does not usually occur in the hypothetical supratentorial language area or nearby regions. This study aimed to evaluate the effect of cerebro-cerebellar language fMRI lateralization in patients with TLE. The neuroimaging study of the verb generation task showed that the cerebellum participates in the generation or maintenance of pronunciation and contributes to different cognitive components of language and all aspects of language production [13] . Trimmel depicts the anatomical areas of the frontal lobe associated with language. The frontal lobe comprises several of language-related gyri with different functions. The first is the inferior frontal gyrus (IFG) of speech processing, The second is the superior frontal gyrus (SFG) of the left hemisphere, which is activated during language fluency and auditory and picture naming tasks. The dorsolateral prefrontal cortex is located in the medial prefrontal cortex, which is related to language semantics [19, 20] . Compared with the LTLE group, the functional connections between Cerebelum_3_R and the left frontal pole, left inferior frontal gyrus, and left frontal orbital cortex were decreased in the RTLE group in the seed-to-voxel analysis. In the ROI-to-ROI analysis, the connection map also revealed significant differences between the RTLE group and the HC group in functional connections between the two brain regions. In the RTLE group, the connections of language-related brain network nodes suggested abnormal connections between Cerebelum 9 L and Frontal Sup Med R, and Frontal Sup R, and between cerebelum 9 R, Frontal Sup Med R, and Frontal Sup L. The right hemisphere of patients with RTLE involves more "global" representations, and seizures may be more likely to adversely affect the function of the frontal lobe. The middle temporal gyrus (MTG) integrates semantic and phonological functions, which is crucial for understanding sentences. Language fluency was associated with task-related fMRI inactivation in bilateral anterior MTG. FMRI with auditory naming task showed increased activation in the anterior and posterior segments of the left MTG [20] . ROI-to-ROI analysis revealed that compared with the HC group, the functional connections between the left middle temporal gyrus (Temporal Pol Mid L) and the Language.pSTG r and between the right middle temporal gyrus (Temporal Pol Mid R) and the language network Language.pSTG l/r decreased in the RTLE group. Thus, a decreased connection between bilateral MTG and language network may be a feature of language reorganization and is related to increased risk of language disorder in TLE. However, individual differences are still an important factor. The cortical area related to language in the parietal lobe contains the angular gyrus (AG), which can be considered a continuation of the superior temporal gyrus / middle gyrus entering the inferior parietal lobule as a cross-pattern hub. AG acts as the visual memory center of words, translating written language into spoken language. AG participates in understanding pronunciation and written language when semantic associations occur [21] . In patients with TLE, there are few studies on the language function of AG. Regarding the role of AG in automatically retrieving specific concepts from semantic associations, we found that the functional connectivity between Vermis10 and right AG in patients with RTLE was lower than that in the HC group. Considering the role of AG, the functional and structural reorganization of AG in RTLE, and the participation of the contralateral hemisphere in the formation of semantic concepts may be critical for language reorganization. With Cerebelum_3_R as the seed point, the results of seed-to-voxel showed that the functional connection difference between the three groups was located in the left frontal pole and left inferior frontal gyrus. With Cerebelum_7_L as the seed point, the functional connection difference among the three groups was located in the right frontal pole. The analysis of language-related brain network node connections in the RTLE group by ROI-to-ROI suggested that there were abnormal connections between Cerebelum 9L, Frontal Sup Med R, and Frontal Sup R, and between Cerebelum 9R and Frontal Sup L. These results suggest that there is a significant dependence on language lateralization between cerebellum and cerebrum in patients with unilateral TLE, which is consistent with the results of previous studies on healthy left-handed and right-handed people with typical language representations [18, 22] . In addition, we found that in almost all cases of lateralized cerebellar activation, there was a crossed cerebellar-cerebellar lateralization pattern regardless of whether the language representation was typical or atypical. According to previous studies, the language laterality of the brain can be considered contralateral in the presence of obvious cerebellar lateralization. Therefore, cerebellar language lateralization can be used as an additional diagnostic measure to determine the hemispheres with language dominance in individuals with typical or atypical language representations. The results showed that the cerebellum can provide an additional diagnostic measure assess hemispheres with to evaluate language dominance. In this study, the connection map between the RTLE group and the HC group revealed significant differences in functional connections between the two brain regions, while no significant differences were found between the LTLE group and the RTLE group, and between the LTLE group and the HC group. The spread of epileptic activity in the brain might be due to an asymmetry on the left side, which can explain more extensive changes in the left hemisphere [23] . The right hemisphere plays a protective role in preventing TLE from spreading to other cortical areas and compensating for cerebral dysfunction caused by epilepsy. The concepts of epileptic spread from left brain stimulation and epileptic protection of the right brain may be complementary rather than competitive. The left prefrontal lobe plays a key role when an individual with left language processing gets involved in the semantic processing during reading, especially in semantic information processing. When the prefrontal lobe of the left or right brain is damaged, semantic and language processing is expected to mainly depend on the contralateral hemisphere [24, 25] . The equipotential model of language suggests that the other hemisphere will develop language processing ability in the opposite direction when the dominant hemisphere of language is impaired in the early stage of development [26] . According to these studies, the negative effects of epileptic activity in one temporal lobe may lead to functional reorganization from one hemisphere to another [8] . These findings also indicate the potential predictive use of naming fMRI tasks in RTLE, and it is necessary to conduct studies with larger sample sizes in the future to confirm these findings. In patients with RTLE, we also observed more areas with increased functional connections between the two brain regions. Englot, Konrad, and Morgan [27] suggested that the increased effect of FC in peripheral dysfunctional areas may be related to the generation and spread of seizure, which may lead to neuronal loss. Then, they produce new excitatory synaptic and axonal burst buds. However, most of these newly formed synapses are anatomically and functionally abnormal. This well-described phenomenon of reactive plasticity can biologically explain increased FC in areas around the dysfunctional area. Englot et al. revealed that reactive plasticity is the source of epileptic persistence. In this study, we observed different patterns of FC changes according to the lateralization of epilepsy. Compared with the HC group, the RTLE group showed more obvious language FC recombination than the LTLE group. This study also has some limitations. First, patients with TLE may have different macroscopic network changes, depending on the hippocampal subregions affected by sclerosis. In addition, other factors may also affect patient connectivity, such as sex and age, left or right chirality, age of seizures, duration of epilepsy, antiepileptic drugs, and intermittent epileptic discharges. Although we controlled these factors, the effect of their persistent interaction on FC recombination and modulation should be assessed in future studies. 5 Conclusion In conclusion, this study showed that compared with patients with LTLE and HCs, patients with RTLE exhibited stronger activation of brain regions related to language (left frontal pole, left inferior frontal gyrus, and left frontoorbital cortex) in the left hemispher. On a finer scale (i.e., at the nodal level), based on the hemispherical lateralization of epilepsy and the spatial topology of language-related dysfunction, patients with RTLE had a more pronounced global disturbance of the language center (right medial superior frontal gyrus, right dorsolateral superior frontal gyrus, left dorsolateral superior frontal gyrus, left posterior parietal lobe of the frontal parietal network, and right angular gyrus) compared with the control group. We found that the cerebellar region has different connectivity patterns between LTLE and RTLE groups. Cerebral diseases, such as TLE, may lead to functional reorganization and transfer of language dominance to homologous regions in the other hemisphere. Declarations Data availability statement The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. Consent to participate Informed consent was obtained from all individual participants included in the study. Ethics approval Approval was obtained from the ethics committee of the First Affiliated Hospital of Guangxi Medical University. The procedures used in this study adhere to the tenets of the Declaration of Helsinki. Clinical trial number: not applicable. Funding This research was supported by the Self-funded Research Project of Health Commission of Guangxi (contract authorization number: Z-F20241850), Natural Science Foundation of Guangxi (contract authorization number: 2024GXNSFAA999103), Natural Science Foundation of Guangxi (contract authorization number: 2024GXNSFAA010265), National Natural Science Foundation of China (contract authorization number:81560223) . References Schneider F, Marcotte K, Brisebois A, et al. Neuroanatomical Correlates of Macrolinguistic Aspects in Narrative Discourse in Unilateral Left and Right Hemisphere Stroke: A Voxel-Based Morphometry Study [J]. Journal of Speech, Language, and Hearing Research, 2021, 64(5): 1650-65. Dijkstra K K, Ferrier C H. Patterns and predictors of atypical language representation in epilepsy [J]. J Neurol Neurosurg Psychiatry, 2013, 84(4): 379-85. Code C. Right hemisphere and verbal communication [J]. Trends in Neurosciences, 1991, 14(3): 121-. Chiarello C. On codes of meaning and the meaning of codes: Semantic access and retrieval within and between hemispheres [J]. 1998. Grindrod C M, Baum S R. Sensitivity to local sentence context information in lexical ambiguity resolution: evidence from left- and right-hemisphere-damaged individuals [J]. Brain Lang, 2003, 85(3): 503-23. Jokeit H, Seitz R J, Markowitsch H J, et al. Prefrontal asymmetric interictal glucose hypometabolism and cognitive impairment in patients with temporal lobe epilepsy [J]. Brain, 1997, (12): 2283-94. Thivard L, Hombrouck J, du Montcel S T, et al. Productive and perceptive language reorganization in temporal lobe epilepsy [J]. Neuroimage, 2005, 24(3): 841-51. Neudorf J, Kress S, Gould L, et al. Language lateralization differences between left and right temporal lobe epilepsy as measured by overt word reading fMRI activation and DTI structural connectivity [J]. Epilepsy & Behavior, 2020, 112. Zimmermann N, Branco L, Ska B, et al. Verbal Fluency in Right Brain Damage: Dissociations Among Production Criteria and Duration [J]. Applied Neuropsychology: Adult, 2013, 21(4): 260-8. Streng M L, Krook-Magnuson E. The cerebellum and epilepsy [J]. Epilepsy & Behavior, 2021, 121. Kros L, Lindeman S, Eelkman Rooda O H J, et al. Synchronicity and Rhythmicity of Purkinje Cell Firing during Generalized Spike-and-Wave Discharges in a Natural Mouse Model of Absence Epilepsy [J]. Frontiers in Cellular Neuroscience, 2017, 11. Guell X, Gabrieli J D E, Schmahmann J D. Triple representation of language, working memory, social and emotion processing in the cerebellum: convergent evidence from task and seed-based resting-state fMRI analyses in a single large cohort [J]. NeuroImage, 2018, 172: 437-49. Méndez Orellana C, Visch-Brink E, Vernooij M, et al. Crossed Cerebrocerebellar Language Lateralization: An Additional Diagnostic Feature for Assessing Atypical Language Representation in Presurgical Functional MR Imaging [J]. American Journal of Neuroradiology, 2015, 36(3): 518-24. Rebecca W. Cheung M-C C, Agnes S. Chan. Confrontation naming in Chinese patients with left,right or bilateral brain damage [J]. Journal of the International Neuropsychological Society, 2004, 10: 46-53. Tatia Lee K Y, Chetwyn Chan. Normative Data for Neuropsychological Measures of Fluency, Attention, and Memory Measures for Hong Kong Chinese [J]. Journal of Clinical and Experimental Neuropsychology, 2002, 24(5): 615-32. Erickson T, Malek-Ahmadi M, Luft C A, et al. Word Fluency Test (WFT): A parallel FAS alternative [J]. Applied Neuropsychology: Adult, 2022: 1-10. Jeffrey R. Binder J A F, Thomas A. Hammeke Robert W. Cox, Stephen M. Rao, and Thomas Prieto. Human Brain Language Areas Identified by Functional Magnetic Resonance Imaging [J]. The Journal of Neuroscience, 1997, 17(1): 353-62. Petra Hubrich-Ungureanu N K, Fritz A. Henn, Dieter F. Braus. Lateralized organization of the cerebellum in a silent verbal fluency task: a functional magnetic resonance imaging study in healthy volunteers [J]. Neuroscience Letters, 2002, 319(2): 91–4. Trimmel K, van Graan L A, Gonzálvez G G, et al. Naming fMRI predicts the effect of temporal lobe resection on language decline [J]. Annals of Clinical and Translational Neurology, 2019, 6(11): 2186-96. Binding L P, Dasgupta D, Giampiccolo D, et al. Structure and function of language networks in temporal lobe epilepsy [J]. Epilepsia, 2022, 63(5): 1025-40. Seghier M L. The Angular Gyrus [J]. The Neuroscientist, 2012, 19(1): 43-61. Jansen A, Flöel A, Van Randenborgh J, et al. Crossed cerebro–cerebellar language dominance [J]. Human Brain Mapping, 2004, 24(3): 165-72. Ridley B G Y, Rousseau C, Wirsich J, et al. Nodal approach reveals differential impact of lateralized focal epilepsies on hub reorganization [J]. NeuroImage, 2015, 118: 39-48. Engel J, Jr, Thompson P M, et al. Connectomics and epilepsy [J]. Current Opinion in Neurology, 2013, 26(2): 186-94. Royer J, Bernhardt B C, Larivière S, et al. Epilepsy and brain network hubs [J]. Epilepsia, 2022, 63(3): 537-50. de Bode S, Chanturidze M, Mathern G W, et al. Literacy after cerebral hemispherectomy: Can the isolated right hemisphere read? [J]. Epilepsy & Behavior, 2015, 45: 248-53. Englot D J, Konrad P E, Morgan V L. Regional and global connectivity disturbances in focal epilepsy, related neurocognitive sequelae, and potential mechanistic underpinnings [J]. Epilepsia, 2016, 57(10): 1546-57. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5397184","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":388747374,"identity":"adc90142-0a93-41bf-b83f-08fb4bbd4406","order_by":0,"name":"Linlin Pang","email":"","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Linlin","middleName":"","lastName":"Pang","suffix":""},{"id":388747375,"identity":"480289bf-03eb-4cc2-b9d0-0750ce8e740d","order_by":1,"name":"Zirong Chen","email":"","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zirong","middleName":"","lastName":"Chen","suffix":""},{"id":388747376,"identity":"ebc6f1e4-fd45-414c-a1d2-388bdc340265","order_by":2,"name":"Binglin Fan","email":"","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Binglin","middleName":"","lastName":"Fan","suffix":""},{"id":388747377,"identity":"64e51eb7-9433-4b9d-aebf-7e6e52215166","order_by":3,"name":"Zexiang Chen","email":"","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zexiang","middleName":"","lastName":"Chen","suffix":""},{"id":388747378,"identity":"c2f5cc8e-be4d-46d1-9562-2634fc915623","order_by":4,"name":"Xiaomin Pang","email":"","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xiaomin","middleName":"","lastName":"Pang","suffix":""},{"id":388747379,"identity":"21aae40e-1ec1-4565-ba1d-3be88c39e30f","order_by":5,"name":"Zhao Zhang","email":"","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zhao","middleName":"","lastName":"Zhang","suffix":""},{"id":388747380,"identity":"9fc09ec0-09fb-414f-bef7-87ec8f79b86d","order_by":6,"name":"Cai Zhong","email":"","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Cai","middleName":"","lastName":"Zhong","suffix":""},{"id":388747381,"identity":"b29f4007-8efc-4eaf-a977-08c1d2e412a3","order_by":7,"name":"Jinou Zheng","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzElEQVRIiWNgGAWjYBACxmYwdQCImQ8c+PCDNC1siQdn9hBvGUgLj/FhDjYi1DK38x58zPPnjpw5/5oPhxl4GOT5xQ4QchhfsjEPzzNjyxlvNxwusGAwnDk7gZAWHjNpHonDiRtunN1weAYPQ4LBbaK0GByu33DjzIPDPGxEa0k4nGBwvoeBaC3GhnMOHDbccIPNABjIEoT9Yth/xvDBmz+H5Q3OH3784cMPG3l+aUJaGmAsCbBKCfzKQUAezuI/QFj1KBgFo2AUjEwAAA4+R+UbptFiAAAAAElFTkSuQmCC","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":true,"prefix":"","firstName":"Jinou","middleName":"","lastName":"Zheng","suffix":""}],"badges":[],"createdAt":"2024-11-05 16:53:30","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5397184/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5397184/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":71740291,"identity":"1b56cda4-e619-4b38-92ef-ba26eb5ef1d6","added_by":"auto","created_at":"2024-12-18 08:05:48","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":621708,"visible":true,"origin":"","legend":"\u003cp\u003eBrain surface map for comparing functional connectivity between groups. (A) Taking Cerebelum_3_R as seed, the difference in functional connection between LTLE, RTLE, and HC groups was in the left frontal pole and left inferior frontal gyrus; (B) With Cerebelum_7_L as seed, the difference in functional connection between the three groups was located in the right frontal pole; (C) With Cerebelum_Crus2_R as seed, the difference in functional connection between the three groups was in the right frontal pole. Warm colors indicate increased functional connectivity. FDR correction, p \u0026lt; 0. 05.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-5397184/v1/81bd8530d233da58d465ea5e.png"},{"id":71741515,"identity":"9b1ae2af-f8ca-439b-bcdb-50d781fab6cb","added_by":"auto","created_at":"2024-12-18 08:13:48","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":611197,"visible":true,"origin":"","legend":"\u003cp\u003eBrain surface map for comparing of functional connectivity between the two groups. T-test showed that P \u0026lt; 0.05, FDR correction. (A). Compared with the HC group, the functional connection between Cerebelum_Crus2_R and the right frontal pole decreased in the LTLE group. (B). Compared with the HC group, the functional connection between Cerebelum_Crus2_R and the right frontal pole decreased in the RTLE group. (C).Compared with the HC group, the functional connection between Cerebelum_7_L and right frontal pole decreased in LTLE group, (D). Compared with the HC group, the functional connection between Cerebelum_7_L and the right frontal pole decreased in the RTLE group. (E). Compared with the LTLE group, the functional connection between Cerebelum_3_R and left frontal pole, left inferior frontal gyrus and left frontoorbital cortex decreased in the RTLE group. Cool colors show decreased functional connectivity.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-5397184/v1/221400c766751848a209c817.png"},{"id":71740296,"identity":"730c0a2a-6dcb-444d-a187-97dcd0b3683b","added_by":"auto","created_at":"2024-12-18 08:05:48","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":8605547,"visible":true,"origin":"","legend":"\u003cp\u003eChord diagram of the ROI-to-ROI FC z-score showing a significant difference between RTLE patients and HCs. The abbreviation outside the circle stands for 23 AAL cerebral regions. The red line indicates increased FC and the blue line indicates decreased FC in patients with RTLE compared with HCs. Abbreviation: ROI, region-of-interest; FC, functional connectivity; TLE, temporal lobe epilepsy; HC: healthy controls.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-5397184/v1/3b407de2581480271ca67c25.png"},{"id":100367340,"identity":"1428b71b-d716-4ec0-84ca-7203b45e04a5","added_by":"auto","created_at":"2026-01-16 07:56:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":9799311,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5397184/v1/3525c8f0-09a0-4bd7-8ad1-206d5fab82b7.pdf"},{"id":71740295,"identity":"1f75b8af-ec1e-46a9-8b63-a9b61d25da1e","added_by":"auto","created_at":"2024-12-18 08:05:48","extension":"docx","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":13589,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-5397184/v1/3c5fcccb29a66d2c2906af21.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effect and mechanism of lateralization of cerebellar-cerebellar network abnormalities on language in patients with unilateral temporal lobe epilepsy","fulltext":[{"header":"1 Introduction","content":"\u003cp\u003eIn most cases, language ability manifests in two well-defined regions of the left hemisphere : Broca's area in the inferior frontal gyrus and Wernicke's area in the superior temporal gyrus\u003csup\u003e[1]\u003c/sup\u003e. However, there is a higher proportion of atypical verbal presentations in patients with epilepsy. This may include abnormal presentations of the language dominant hemisphere or atypical lateralization\u003csup\u003e[2]\u003c/sup\u003e. Although the role of the left hemisphere in understanding language is well established, a growing number of scholars support the idea that the right hemisphere has a similar role in word-semantic processing\u003csup\u003e[3, 4]\u003c/sup\u003e. Studies have shown that damage to both the left hemisphere (LH) and right hemisphere (RH) of the brain impairs the resolution of ambiguous words in context. Moreover, the deficiencies in both groups focus on difficulties in using contextual information. Left hemisphere\u0026rsquo;s impairment can impair the initial ability to integrate semanteme into context, while also producing a faster-than-normal decline in word activation. Damage to the right hemisphere can also impair the initial acquisition of contextual information and lead to a reliance on frequency-based lexical activation. Both hemispheres need access to contextual information to successfully accomplish ambiguity resolution. The two hemispheres work together and play an important role in the process of resolution\u003csup\u003e[5]\u003c/sup\u003e. The distance between the language area and the epileptic focus in patients with TLE indicates that cerebral dysfunction occurs in a region outside the epileptic area without structural abnormalities. In fact, metabolic disorders have been observed in the temporal and frontal regions beyond the damaged temporal lobe\u003csup\u003e[6]\u003c/sup\u003e. Since lateralization of speech in epileptic patients is associated with different levels of cerebral dysfunction, there may be a recombination of language circuits in the course of epilepsy, and the recombination of language circuits to the right hemisphere may represent an adaptive process\u003csup\u003e[7]\u003c/sup\u003e. Neudorf et al. found that patients with RTLE exhibit stronger LH activation in language-related brain regions (tegmentum and fusiform gyrus) than patients with LTLE and HCs\u003csup\u003e[8]\u003c/sup\u003e. Zimmermann et al. \u003csup\u003e[9]\u003c/sup\u003e assessed the use of language fluency in 40 adults with vascular injury in the right hemisphere. The results showed that the patient group showed a greater degree of impairment in semantic fluency tasks. These studies show that there are differences in language lateralization between patients with LTLE and RTLE.\u003c/p\u003e \u003cp\u003eCombined with changes in cerebellar activity during seizures, Martha et al. suggested that the cerebellum may be a potential therapeutic target for controlling epilepsy\u003csup\u003e[10, 11]\u003c/sup\u003e. Different regions of the cerebellar cortex are involved in motor, language, working memory, social and emotional tasks. Non-motor processing mainly occurs in lobule VI, Crus I/II, VIIB, IX, and X\u003csup\u003e[12]\u003c/sup\u003e. Both the cerebral hemispheres and the cerebellum are activated when performing specific language tasks. A stronger laterality of language to the cerebral hemisphere predicts a stronger laterality to the contralateral cerebellar hemisphere. In almost all cases of lateralization of cerebellar activation, there is a crossed cerebellar-cerebellar lateralization pattern regardless of whether the language presentation is typical or atypical. According to previous studies, when the cerebellum is obviously lateralized, the language laterality of the brain can be considered contralateral\u003csup\u003e[13]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eWe speculate that in patients with TLE and language disorders, the cerebellum is involved during repeated attacks, which may damage the cerebellar language functional network of TLE patients, and lead to differences in cerebellar language functional networks of patients with different literalitiess of TLE. This difference in cerebellar functional brain networks can be used as an additional diagnostic feature to determine hemispheric language advantage in patients with lateralized TLE. Here, we considered the cerebellum as the area of interest to construct cerebellar-brain functional connectivity networks and explore the differences in speech impairment patterns in patients with TLE and different hemiencephalic episodes.\u003c/p\u003e"},{"header":"2 Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Participants\u003c/h2\u003e \u003cp\u003e Our study was approved by the Ethical Committee of the First Affliated Hospital of Guangxi Medical University, Written informed consent was obtained from each participant.\u003c/p\u003e \u003cp\u003e Fifty-eight patients with TLE in the epilepsy clinic of Department of Neurology of Guangxi Medical University were recruited from 2019 to 2022, including 28 participants in the LTLE group and 30 participants in the RTLE group. All patients with TLE epilepsy were diagnosed by two experienced epilepsy experts according to the diagnostic criteria of the International Anti-Epilepsy Alliance Association. The inclusion criteria for patients with TLE were as follows: (1) age between 18 and 50 years old, and scalp EEG showed epileptic discharge from unilateral temporal lobe during attack or intermission; (2) clinical symptoms of seizure were consistent with temporal lobe seizure and participants understood and signed the experimental informed consent form; (3) regular use of antiepileptic drugs, with no obvious mental illnesses or other serious systemic diseases. (4) except for hippocampal sclerosis, no structural abnormality was found in MRI. The exclusion criteria for patients with TLE were as follows: (1) other systemic, neurological, and mental disorders; (2) diagnosis of multifocal or extratemporal epilepsy; (3) developmental defects, cortical malformations, or other focal lesions in MRI; (4) severe mental disorders or dementia; (5) not cooperating during the examination; (6) any history of drug or alcohol abuse.\u003c/p\u003e \u003cp\u003eThe study included 30 healthy adult participants whose age, sex, and education matched those of patients with TLE. All participants were right-handed and signed written informed consent. This study was approved by the Medical Ethics Committee of Clinical Research of Guangxi Medical University. The normal control group included healthy volunteers whose sex, age and education level matched with those of TLE patients. They were right-handed, with no history of alcohol drinking, drug addiction or dependence, brain trauma or other neuropsychiatric disorders.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Language testing\u003c/h2\u003e \u003cp\u003eUsing the Boston naming test (BNT) due to Chinese culture, 30 items were selected from the 60 original items. For each one of the 30 items, the Chinese name of the object was set as the target response, and a semantic prompt is designed for each response, just like the original version of BNT. The presentation order of the three options for each project (target response, semantic interference, and perceptual interference) was random. The measure of naming performance included the total number of correct items after spontaneous naming, semantic prompt, and multiple selection recognition. If the participant named the project correctly, the assessor continued to test the next project. If the participant wrongly responded, or did not respond within 20 seconds, then a semantic clue was given. If the subject could not correctly say the name of the object after providing the semantic clue, he did not receive a score\u003csup\u003e[14]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003e Verbal fluency test (VFT) is used to measure the spontaneous generation of a certain class of words in a limited time. The Chinese version of VFT was used in this study. The controlled oral vocabulary association test, especially the \"fruit\" category test, was used to assess semantic fluency. The subjects were asked to say as many different fruit names as possible in 1 minute. The test emphasizes the speed of generating the target word as soon as possible, rather than the quality of the answer. The examiner told tell the subject \u0026ldquo;this is a test to see how quickly you can say words that begin with a particular category.\u0026rdquo; The quality of speech is not important.\" VFT instructions include the types of errors to avoid (e.g., proper nouns) and also include error samples to ensure participants fully understand all rules. Temporal changes are not encouraged, and the purpose of these improvements is to ensure that each participant clearly understands that this is a 1-minute speed performance task and which types of responses are acceptable. Before the first test, a sample test of three to four words was conducted to ensure that each participant understood the task and, rebooted if necessary. We also asked participants if they had any questions\u003csup\u003e[15, 16]\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Resting fMRI data acquisition\u003c/h2\u003e \u003cp\u003eMagnetic resonance imaging data \u003cb\u003ew\u003c/b\u003eere collected using an Achievia3.0T magnetic resonance imaging scanner (Philips, Amsterdam, the Netherlands). The 12-channel head phased array surface coil was used for data acquisition. The rs-fMRI scan lasted for 450s and 225 time points were obtained. During the scan, participants were reminded to close their eyes, stay awake and not think about anything. We used headphones and cushions to reduce noise and restrict head movement. We acquired sagittal high-resolution T1-weighted images. The axial T2 fluid-attenuated inversion recovery sequence was then used to remove clinically asymptomatic encephalopathy. The following parameters were adopted for RS-fMRI: repetition time (TR) / echo time (TE)\u0026thinsp;=\u0026thinsp;2000 ms, voxel size\u0026thinsp;=\u0026thinsp;3.44 mm \u0026times; 3.44 mm \u0026times; 4 mm, field of view\u0026thinsp;=\u0026thinsp;220 mm \u0026times; 220 mm, matrix size\u0026thinsp;=\u0026thinsp;64 \u0026times; 64, flip angle\u0026thinsp;=\u0026thinsp;90\u0026deg;, number of slices\u0026thinsp;=\u0026thinsp;41, slice thickness\u0026thinsp;=\u0026thinsp;3.5 mm. slice gap\u0026thinsp;=\u0026thinsp;0.5 mm. The parameters used for high-resolution 3DT1W weighted structural image were as follows: TR/TE\u0026thinsp;=\u0026thinsp;7.8/ 3.4 ms, flip angle\u0026thinsp;=\u0026thinsp;9\u0026deg;, field of view\u0026thinsp;=\u0026thinsp;256 mm \u0026times; 256 mm, image matrix\u0026thinsp;=\u0026thinsp;256 \u0026times; 256, number of slices\u0026thinsp;=\u0026thinsp;176 slices, slice thickness\u0026thinsp;=\u0026thinsp;1 mm, voxel size\u0026thinsp;=\u0026thinsp;1.0 mm \u0026times; 1.0 mm \u0026times; 1.0 mm.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Analysis of resting fMRI data\u003c/h2\u003e \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e \u003ch2\u003e2.4.1 MRI data preprocessing\u003c/h2\u003e \u003cp\u003eBased on the MATLAB R2018b running \"CONN19c toolbox\", we chose seed-based technology. We selected the default parameters to preprocess and analyze data. Preprocessing includeds the following steps: noise source reduction, first-level individual analysis (including correlation analysis), and second-level random effect group analysis, including time layer correction, system odd correction, head motion correction, image registration, image segmentation, spatial standardization, spatial smoothing (FWHM\u0026thinsp;=\u0026thinsp;6mm), and 3D structure T1 weighted co-registration.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section3\"\u003e \u003ch2\u003e2.4.2 Functional connectivity analysis of resting state fMRI\u003c/h2\u003e \u003cp\u003eThe CONN toolbox provides 116 ROIs comprising the cortical and subcortical regions of the AAL template and cerebellar regions. Therefore, 26 cerebellar regions were selected as ROIs. The indexes, names, and MNI coordinates of the 26 cerebellar ROIs used in this study are shown in the supplementary tabl\u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003ee1\u003c/span\u003e. The gray matter, white matter, and cerebrospinal fluid were separated from the image. We conducted noise reduction, primary individual analysis (including correlation analysis) and secondary random effect group analysis. The functional connectivity of network recognition based on ROI correlation analysis mainly focuses on sensorimotor network, language network, visual network, highlight network and default mode network. After selecting the bilateral cerebellum as the ROI, the whole brain could be associated with the time process, thus generating a spatial map of the network of interest. The cerebellar-whole brain functional connection, the correlation maps of the whole brain voxel ROI and ROI were calculated to show the cerebellar-whole brain functional connection. Unwanted head movements, physiological effects, and other noises were removed by linear regression and bandpass filtering. The general linear model weighted regression and correlation measurement were conducted, and the Fisher R to Z transform was used to generate the z graph for each subject. Finally, age, sex, and education level were used as covariates to analyze differences in functional connectivity between the two groups (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05, FDR correction).\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Statistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was conducted using SPSS23.0 software. Demographic, clinical and neuropsychological data were analyzed. Independent sample T test was used to analyze the difference between normal distribution and uniform variance between the two groups. Mann-Whitney test was used for data with no normal distribution or uneven variance. Chi-square test was used for qualitative variables. p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"3 Result","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n\u003ch2\u003e3.1 Demographic, clinical, and behavioral data\u003c/h2\u003e\n\u003cp\u003eTable\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e shows the demographic data and clinical characteristics of 28 patients with LTLE, 30 patients with RTLE, and 30 HC group. There was no statistically significant difference in age, sex, and education level. The BNT and VFT scores of patients with LTLE and RTLE were significantly lower than those of normal controls, but there was no difference between the LTLE group and the RTLE group.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eDemographics, clinical and language scale scores of subjects in three groups\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eVariables\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eLTLE(n\u0026thinsp;=\u0026thinsp;28)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eRTLE(n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eHC(n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP\u003c/p\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\u003cp\u003e\u003cstrong\u003eDemographic characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAge (years)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e30.79\u0026thinsp;\u0026plusmn;\u0026thinsp;8.03\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e30.67\u0026thinsp;\u0026plusmn;\u0026thinsp;9.60\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e27.23\u0026thinsp;\u0026plusmn;\u0026thinsp;5.76\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.155\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSex (male/female)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8/20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11/19\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10/20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.806\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eEducation (years)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical features\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAge at onset (years)\u003c/p\u003e\n\u003cp\u003eEpilepsy duration (years)\u003c/p\u003e\n\u003cp\u003eSeizure type (Focal/FBTCS)\u003c/p\u003e\n\u003cp\u003eAEDs (mono-/polytherapy)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e13.50(9\u0026ndash;15)\u003c/p\u003e\n\u003cp\u003e19.07\u0026thinsp;\u0026plusmn;\u0026thinsp;9.20\u003c/p\u003e\n\u003cp\u003e8.00(5.00-16.25)\u003c/p\u003e\n\u003cp\u003e15/13\u003c/p\u003e\n\u003cp\u003e10/18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e12.00(9\u0026ndash;15)\u003c/p\u003e\n\u003cp\u003e20.10\u0026thinsp;\u0026plusmn;\u0026thinsp;11.11\u003c/p\u003e\n\u003cp\u003e9.50(5.00\u0026ndash;15.00)\u003c/p\u003e\n\u003cp\u003e21/9\u003c/p\u003e\n\u003cp\u003e12/18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e12.00(9\u0026ndash;16)\u003c/p\u003e\n\u003cp\u003eNA\u003c/p\u003e\n\u003cp\u003eNA\u003c/p\u003e\n\u003cp\u003eNA\u003c/p\u003e\n\u003cp\u003eNA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.938\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e0.704d\u003c/p\u003e\n\u003cp\u003e0.981c\u003c/p\u003e\n\u003cp\u003eNA\u003c/p\u003e\n\u003cp\u003eNA\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNeuropsychological test\u003c/strong\u003e\u003c/p\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\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBNT\u003c/p\u003e\n\u003cp\u003eVFT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e25(22.25\u0026ndash;27.75)\u003c/p\u003e\n\u003cp\u003e10.32\u0026thinsp;\u0026plusmn;\u0026thinsp;3.80\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24.00(20.00\u0026ndash;27.00)\u003c/p\u003e\n\u003cp\u003e10.37\u0026thinsp;\u0026plusmn;\u0026thinsp;3.98\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e29(27.75-30)\u003c/p\u003e\n\u003cp\u003e15.63\u0026thinsp;\u0026plusmn;\u0026thinsp;3.35\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.000e*\u003c/p\u003e\n\u003cp\u003e0.000a*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eData are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation and median (upper and lower quartile). a: one-way ANOVA was used to compare groups; b: \u0026chi; 2 test was used to measure the significance level; c: Mann-Whitney test was used to measure the significance level; d: independent sample t test was used to measure the significance level; e: Kruskal-Wallis test was used. There was a significant difference (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). *. Post-mortem analysis showed that there were significant differences between patients with LTLE and RTLE and HCs. LTLE: left temporal lobe epilepsy; RTLE: right temporal lobe epilepsy; HC: healthy control; FBTCS: focal to bilateral tonic-clonic seizures; FD: frame-wise displacement; AEDs: antiepileptic drugs; NA, unavailable; BNT: Boston naming test; VFT: verbal fluency test.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n\u003ch2\u003e3.2 Functional connectivity analysis\u003c/h2\u003e\n\u003cdiv id=\"Sec13\" class=\"Section3\"\u003e\n\u003ch2\u003e3.2.1 Seed- to-Voxel result\u003c/h2\u003e\n\u003cp\u003eWe set the seed point to the bilateral cerebellar region for functional connectivity analysis. The functional connections of Cerebelum_3_R, Cerebelum_7_L, and Cerebelum_Crus 2_R were significantly different between the three groups (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). When Cerebelum_Crus2_R was used as ROI, the right frontal functional connection of patients with LTLE and RTLE was lower than that of the HC group. There was no difference between the RTLE and LTLE groups (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eA and B). When Cerebelum_7_L was used as ROI, the right frontal functional connection of LTLE and RTLE patients was lower than that of the HC group, but there was no difference between the RTLE and LTLE groups (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eC, D). When Cerebelum_3_R was used as ROI, the functional connections of left frontal pole, left inferior frontal gyrus and left fronto-orbital cortex in the RTLE group were lower than those in the LTLE group (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eE). Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e shows the details of the brain regions with abnormal FC intensity. The above results show language lateralization in the cerebrum and cerebellum of patients with TLE. When Cerebelum_3_R and Cerebelum_7_L were used as seeds, cross cerebrocerebellar activation was found in both RTLE and LTLE patients. When Cerebelum_Crus2_R was used as the seed, patients showed language lateralization to the same side in the cerebellum and cerebral cortex.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eDifferences in resting state FC among the three groups (GroupANOVA)\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSeed Region\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCluster Coordinates\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCluster Size\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCluster Regions\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCluster p-Value(FDR)\u003c/p\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\u003cp\u003eCerebelum_3_R\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e-48\u0026thinsp;+\u0026thinsp;44\u0026thinsp;\u0026minus;\u0026thinsp;04\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e352\u003c/p\u003e\n\u003cp\u003e72\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eFrontal Pole Left\u003c/p\u003e\n\u003cp\u003eInferior Frontal Gyrus Left\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.000029\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCerebelum_7_L\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e+\u0026thinsp;20\u0026thinsp;+\u0026thinsp;62\u0026thinsp;\u0026minus;\u0026thinsp;16\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e206\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eFrontal Pole Right\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.014566\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCerebelum_Crus2_R\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e+\u0026thinsp;14\u0026thinsp;+\u0026thinsp;62\u0026thinsp;+\u0026thinsp;04\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e181\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eFrontal Pole Right\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.015814\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"7\"\u003eResults were corrected by FDR, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05. There were significant differences (excluding gender, age, education and cephalomotor factors). ANOVA: analysis of variance\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eDifferences in resting state FC among the three groups(Post hoc t-test)\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSeed Region\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eGroup\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCluster Coordinates\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCluster Size\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCluster Regions\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCluster p-Value(FDR)\u003c/p\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\u003cp\u003eCerebelum_3_R\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eLTLE vs RTLE\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-48\u0026thinsp;+\u0026thinsp;44\u0026thinsp;\u0026minus;\u0026thinsp;14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e416\u003c/p\u003e\n\u003cp\u003e94\u003c/p\u003e\n\u003cp\u003e73\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003eFrontal Pole Left\u003c/p\u003e\n\u003cp\u003eInferior Frontal Gyrus Left\u003c/p\u003e\n\u003cp\u003eFrontal Orbital Cortex Left\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.000010\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eLTLE vs HC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003en.s.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003en.s.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003en.s.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003en.s.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eRTLE vs HC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003en.s.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003en.s.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003en.s.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003en.s.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCerebelum_7_L\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eLTLE vs RTLE\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003en.s.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003en.s.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003en.s.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003en.s.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eLTLE vs HC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+\u0026thinsp;24\u0026thinsp;+\u0026thinsp;62\u0026thinsp;\u0026minus;\u0026thinsp;12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e176\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003eFrontal Pole Right\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.034397\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eRTLE vs HC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+\u0026thinsp;20\u0026thinsp;+\u0026thinsp;60\u0026thinsp;\u0026minus;\u0026thinsp;16\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e198\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003eFrontal Pole Right\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.017768\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCerebelum_Crus2_R\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eLTLE vs RTLE\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003en.s.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003en.s.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003en.s.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003en.s.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eLTLE vs HC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+\u0026thinsp;14\u0026thinsp;+\u0026thinsp;62\u0026thinsp;+\u0026thinsp;02\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e170\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003eFrontal Pole Right\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.021973\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eRTLE vs HC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+\u0026thinsp;16\u0026thinsp;+\u0026thinsp;36\u0026thinsp;+\u0026thinsp;44\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e191\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003eFrontal Pole Right\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.047409\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eResults were corrected by FDR, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05. There were significant differences (excluding gender, age, education and cephalomotor factors). n.s.: no significance was found.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\" class=\"Section3\"\u003e\n\u003ch2\u003e3.2.1 ROI-to-ROI result\u003c/h2\u003e\n\u003cp\u003eThe connection map between the RTLE group and the HC group revealed significant differences in functional connections between the two brain regions (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). Specifically, it shows a Chord diagram of the ROI-to-ROI analysis after FDR correction for P-values. Compared with the HC group, the connections that significantly decreased the FC of language-related brain network nodes in the RTLE group were mainly between Cerebelum9L and Frontal Sup MedR, Frontal Sup R; between Cerebelum9R, right medial superior frontal gyrus, and left dorsolateral superior frontal gyrus (Frontal Sup L); between Vermis 9 and FrontoParietal.PPC L); between Vermis10 and Angular R; between Temporal Pol Mid L and Language.Pstg r; between Temporal Pol Mid R and Language.Pstg l/r. The language network consisted of bilateral inferior frontal gyrus (IFG) and bilateral superior temporal gyrus (STG), which were selected from the default automatic templates provided in the Conn toolbox. In terms of functional connections, no significant differences were found between the LTLE and RTLE groups or between LTLE and HC groups.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eIn this study, the functional cerebrocerebellar connections related to language in patients with LTLE and RTLE were analyzed at the baseline level of the resting brain. We found abnormalities in the functional connections between the cerebellum and the language network.\u003c/p\u003e \u003cp\u003eFunctional magnetic resonance imaging (fMRI) is a feasible neuroimaging tool for diagnosing hemispheric language dominance. Spontaneous neural activity in the resting state can also be considered the baseline activity of the brain. Comparing blood oxygen concentration- dependent (BOLD) levels between different parts of the brain shows a certain regulatory system and organization. There are also some similarities in this activation mode, known as brain network activity in the resting state. It is correctly verified by cortical electrical stimulation\u003csup\u003e[13]\u003c/sup\u003e. Outside the traditional \"Wernicke area\", there is a language area in the temporoparietal of the left hemisphere, namely the middle temporal gyrus, inferior temporal gyrus, fusiform gyrus and angular gyrus. Outside the classic \"Broca area\", the left prefrontal lobe has a wide range of language areas\u003csup\u003e[17]\u003c/sup\u003e. In individuals with left-hemisphere language dominance, this task has been shown to activate the right cerebellum. Petra et al. indicated the patterns of cerebellar cross language lateralization in healthy individuals, including typical left-sided language lateralization and atypical right-sided language lateralization\u003csup\u003e[18]\u003c/sup\u003e. Atypical language may manifest as a transfer of language function to the contralateral hemisphere or to the ipsilateral language area, or both. This cerebellar crossover language lateralization may be a useful diagnostic feature for determining language hemispheric dominance in patients with TLE, as cerebro-cerebellar language activation does not usually occur in the hypothetical supratentorial language area or nearby regions. This study aimed to evaluate the effect of cerebro-cerebellar language fMRI lateralization in patients with TLE.\u003c/p\u003e \u003cp\u003eThe neuroimaging study of the verb generation task showed that the cerebellum participates in the generation or maintenance of pronunciation and contributes to different cognitive components of language and all aspects of language production\u003csup\u003e[13]\u003c/sup\u003e. Trimmel depicts the anatomical areas of the frontal lobe associated with language. The frontal lobe comprises several of language-related gyri with different functions. The first is the inferior frontal gyrus (IFG) of speech processing, The second is the superior frontal gyrus (SFG) of the left hemisphere, which is activated during language fluency and auditory and picture naming tasks. The dorsolateral prefrontal cortex is located in the medial prefrontal cortex, which is related to language semantics\u003csup\u003e[19, 20]\u003c/sup\u003e. Compared with the LTLE group, the functional connections between Cerebelum_3_R and the left frontal pole, left inferior frontal gyrus, and left frontal orbital cortex were decreased in the RTLE group in the seed-to-voxel analysis. In the ROI-to-ROI analysis, the connection map also revealed significant differences between the RTLE group and the HC group in functional connections between the two brain regions. In the RTLE group, the connections of language-related brain network nodes suggested abnormal connections between Cerebelum 9 L and Frontal Sup Med R, and Frontal Sup R, and between cerebelum 9 R, Frontal Sup Med R, and Frontal Sup L. The right hemisphere of patients with RTLE involves more \"global\" representations, and seizures may be more likely to adversely affect the function of the frontal lobe.\u003c/p\u003e \u003cp\u003eThe middle temporal gyrus (MTG) integrates semantic and phonological functions, which is crucial for understanding sentences. Language fluency was associated with task-related fMRI inactivation in bilateral anterior MTG. FMRI with auditory naming task showed increased activation in the anterior and posterior segments of the left MTG\u003csup\u003e[20]\u003c/sup\u003e. ROI-to-ROI analysis revealed that compared with the HC group, the functional connections between the left middle temporal gyrus (Temporal Pol Mid L) and the Language.pSTG r and between the right middle temporal gyrus (Temporal Pol Mid R) and the language network Language.pSTG l/r decreased in the RTLE group. Thus, a decreased connection between bilateral MTG and language network may be a feature of language reorganization and is related to increased risk of language disorder in TLE. However, individual differences are still an important factor.\u003c/p\u003e \u003cp\u003eThe cortical area related to language in the parietal lobe contains the angular gyrus (AG), which can be considered a continuation of the superior temporal gyrus / middle gyrus entering the inferior parietal lobule as a cross-pattern hub. AG acts as the visual memory center of words, translating written language into spoken language. AG participates in understanding pronunciation and written language when semantic associations occur\u003csup\u003e[21]\u003c/sup\u003e. In patients with TLE, there are few studies on the language function of AG. Regarding the role of AG in automatically retrieving specific concepts from semantic associations, we found that the functional connectivity between Vermis10 and right AG in patients with RTLE was lower than that in the HC group. Considering the role of AG, the functional and structural reorganization of AG in RTLE, and the participation of the contralateral hemisphere in the formation of semantic concepts may be critical for language reorganization.\u003c/p\u003e \u003cp\u003eWith Cerebelum_3_R as the seed point, the results of seed-to-voxel showed that the functional connection difference between the three groups was located in the left frontal pole and left inferior frontal gyrus. With Cerebelum_7_L as the seed point, the functional connection difference among the three groups was located in the right frontal pole. The analysis of language-related brain network node connections in the RTLE group by ROI-to-ROI suggested that there were abnormal connections between Cerebelum 9L, Frontal Sup Med R, and Frontal Sup R, and between Cerebelum 9R and Frontal Sup L. These results suggest that there is a significant dependence on language lateralization between cerebellum and cerebrum in patients with unilateral TLE, which is consistent with the results of previous studies on healthy left-handed and right-handed people with typical language representations\u003csup\u003e[18, 22]\u003c/sup\u003e. In addition, we found that in almost all cases of lateralized cerebellar activation, there was a crossed cerebellar-cerebellar lateralization pattern regardless of whether the language representation was typical or atypical. According to previous studies, the language laterality of the brain can be considered contralateral in the presence of obvious cerebellar lateralization. Therefore, cerebellar language lateralization can be used as an additional diagnostic measure to determine the hemispheres with language dominance in individuals with typical or atypical language representations. The results showed that the cerebellum can provide an additional diagnostic measure assess hemispheres with to evaluate language dominance.\u003c/p\u003e \u003cp\u003eIn this study, the connection map between the RTLE group and the HC group revealed significant differences in functional connections between the two brain regions, while no significant differences were found between the LTLE group and the RTLE group, and between the LTLE group and the HC group. The spread of epileptic activity in the brain might be due to an asymmetry on the left side, which can explain more extensive changes in the left hemisphere\u003csup\u003e[23]\u003c/sup\u003e. The right hemisphere plays a protective role in preventing TLE from spreading to other cortical areas and compensating for cerebral dysfunction caused by epilepsy. The concepts of epileptic spread from left brain stimulation and epileptic protection of the right brain may be complementary rather than competitive. The left prefrontal lobe plays a key role when an individual with left language processing gets involved in the semantic processing during reading, especially in semantic information processing. When the prefrontal lobe of the left or right brain is damaged, semantic and language processing is expected to mainly depend on the contralateral hemisphere\u003csup\u003e[24, 25]\u003c/sup\u003e. The equipotential model of language suggests that the other hemisphere will develop language processing ability in the opposite direction when the dominant hemisphere of language is impaired in the early stage of development\u003csup\u003e[26]\u003c/sup\u003e. According to these studies, the negative effects of epileptic activity in one temporal lobe may lead to functional reorganization from one hemisphere to another\u003csup\u003e[8]\u003c/sup\u003e. These findings also indicate the potential predictive use of naming fMRI tasks in RTLE, and it is necessary to conduct studies with larger sample sizes in the future to confirm these findings.\u003c/p\u003e \u003cp\u003eIn patients with RTLE, we also observed more areas with increased functional connections between the two brain regions. Englot, Konrad, and Morgan\u003csup\u003e[27]\u003c/sup\u003e suggested that the increased effect of FC in peripheral dysfunctional areas may be related to the generation and spread of seizure, which may lead to neuronal loss. Then, they produce new excitatory synaptic and axonal burst buds. However, most of these newly formed synapses are anatomically and functionally abnormal. This well-described phenomenon of reactive plasticity can biologically explain increased FC in areas around the dysfunctional area. Englot et al. revealed that reactive plasticity is the source of epileptic persistence. In this study, we observed different patterns of FC changes according to the lateralization of epilepsy. Compared with the HC group, the RTLE group showed more obvious language FC recombination than the LTLE group.\u003c/p\u003e \u003cp\u003eThis study also has some limitations. First, patients with TLE may have different macroscopic network changes, depending on the hippocampal subregions affected by sclerosis. In addition, other factors may also affect patient connectivity, such as sex and age, left or right chirality, age of seizures, duration of epilepsy, antiepileptic drugs, and intermittent epileptic discharges. Although we controlled these factors, the effect of their persistent interaction on FC recombination and modulation should be assessed in future studies.\u003c/p\u003e"},{"header":"5 Conclusion","content":"\u003cp\u003eIn conclusion, this study showed that compared with patients with LTLE and HCs, patients with RTLE exhibited stronger activation of brain regions related to language (left frontal pole, left inferior frontal gyrus, and left frontoorbital cortex) in the left hemispher. On a finer scale (i.e., at the nodal level), based on the hemispherical lateralization of epilepsy and the spatial topology of language-related dysfunction, patients with RTLE had a more pronounced global disturbance of the language center (right medial superior frontal gyrus, right dorsolateral superior frontal gyrus, left dorsolateral superior frontal gyrus, left posterior parietal lobe of the frontal parietal network, and right angular gyrus) compared with the control group. We found that the cerebellar region has different connectivity patterns between LTLE and RTLE groups. Cerebral diseases, such as TLE, may lead to functional reorganization and transfer of language dominance to homologous regions in the other hemisphere.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eApproval was obtained from the ethics committee of the First Affiliated Hospital of Guangxi Medical University. The procedures used in this study adhere to the tenets of the Declaration of Helsinki.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eClinical trial number: not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was supported by the Self-funded Research Project of Health Commission of Guangxi (contract authorization number: Z-F20241850), Natural Science Foundation of Guangxi (contract authorization number: 2024GXNSFAA999103), Natural Science Foundation of Guangxi (contract authorization number: 2024GXNSFAA010265), National Natural Science Foundation of China (contract authorization number:81560223) .\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSchneider F, Marcotte K, Brisebois A, et al. Neuroanatomical Correlates of Macrolinguistic Aspects in Narrative Discourse in Unilateral Left and Right Hemisphere Stroke: A Voxel-Based Morphometry Study [J]. Journal of Speech, Language, and Hearing Research, 2021, 64(5): 1650-65.\u003c/li\u003e\n\u003cli\u003eDijkstra K K, Ferrier C H. Patterns and predictors of atypical language representation in epilepsy [J]. J Neurol Neurosurg Psychiatry, 2013, 84(4): 379-85.\u003c/li\u003e\n\u003cli\u003eCode C. Right hemisphere and verbal communication [J]. Trends in Neurosciences, 1991, 14(3): 121-.\u003c/li\u003e\n\u003cli\u003eChiarello C. On codes of meaning and the meaning of codes: Semantic access and retrieval within and between hemispheres [J]. 1998.\u003c/li\u003e\n\u003cli\u003eGrindrod C M, Baum S R. Sensitivity to local sentence context information in lexical ambiguity resolution: evidence from left- and right-hemisphere-damaged individuals [J]. Brain Lang, 2003, 85(3): 503-23.\u003c/li\u003e\n\u003cli\u003eJokeit H, Seitz R J, Markowitsch H J, et al. Prefrontal asymmetric interictal glucose hypometabolism and cognitive impairment in patients with temporal lobe epilepsy [J]. Brain, 1997, (12): 2283-94.\u003c/li\u003e\n\u003cli\u003eThivard L, Hombrouck J, du Montcel S T, et al. Productive and perceptive language reorganization in temporal lobe epilepsy [J]. Neuroimage, 2005, 24(3): 841-51.\u003c/li\u003e\n\u003cli\u003eNeudorf J, Kress S, Gould L, et al. Language lateralization differences between left and right temporal lobe epilepsy as measured by overt word reading fMRI activation and DTI structural connectivity [J]. Epilepsy \u0026amp; Behavior, 2020, 112.\u003c/li\u003e\n\u003cli\u003eZimmermann N, Branco L, Ska B, et al. Verbal Fluency in Right Brain Damage: Dissociations Among Production Criteria and Duration [J]. Applied Neuropsychology: Adult, 2013, 21(4): 260-8.\u003c/li\u003e\n\u003cli\u003e Streng M L, Krook-Magnuson E. The cerebellum and epilepsy [J]. Epilepsy \u0026amp; Behavior, 2021, 121.\u003c/li\u003e\n\u003cli\u003e Kros L, Lindeman S, Eelkman Rooda O H J, et al. Synchronicity and Rhythmicity of Purkinje Cell Firing during Generalized Spike-and-Wave Discharges in a Natural Mouse Model of Absence Epilepsy [J]. Frontiers in Cellular Neuroscience, 2017, 11.\u003c/li\u003e\n\u003cli\u003e Guell X, Gabrieli J D E, Schmahmann J D. Triple representation of language, working memory, social and emotion processing in the cerebellum: convergent evidence from task and seed-based resting-state fMRI analyses in a single large cohort [J]. NeuroImage, 2018, 172: 437-49.\u003c/li\u003e\n\u003cli\u003e M\u0026eacute;ndez Orellana C, Visch-Brink E, Vernooij M, et al. Crossed Cerebrocerebellar Language Lateralization: An Additional Diagnostic Feature for Assessing Atypical Language Representation in Presurgical Functional MR Imaging [J]. American Journal of Neuroradiology, 2015, 36(3): 518-24.\u003c/li\u003e\n\u003cli\u003e Rebecca W. Cheung M-C C, Agnes S. Chan. Confrontation naming in Chinese patients with left,right or bilateral brain damage [J]. Journal of the International Neuropsychological Society, 2004, 10: 46-53.\u003c/li\u003e\n\u003cli\u003e Tatia Lee K Y, Chetwyn Chan. Normative Data for Neuropsychological Measures of Fluency, Attention, and Memory Measures for Hong Kong Chinese [J]. Journal of Clinical and Experimental Neuropsychology, 2002, 24(5): 615-32.\u003c/li\u003e\n\u003cli\u003e Erickson T, Malek-Ahmadi M, Luft C A, et al. Word Fluency Test (WFT): A parallel FAS alternative [J]. Applied Neuropsychology: Adult, 2022: 1-10.\u003c/li\u003e\n\u003cli\u003e Jeffrey R. Binder J A F, Thomas A. Hammeke Robert W. Cox, Stephen M. Rao, and Thomas Prieto. Human Brain Language Areas Identified by Functional Magnetic Resonance Imaging [J]. The Journal of Neuroscience, 1997, 17(1): 353-62.\u003c/li\u003e\n\u003cli\u003e Petra Hubrich-Ungureanu N K, Fritz A. Henn, Dieter F. Braus. Lateralized organization of the cerebellum in a silent verbal fluency task: a functional magnetic resonance imaging study in healthy volunteers [J]. Neuroscience Letters, 2002, 319(2): 91\u0026ndash;4.\u003c/li\u003e\n\u003cli\u003e Trimmel K, van Graan L A, Gonz\u0026aacute;lvez G G, et al. Naming fMRI predicts the effect of temporal lobe resection on language decline [J]. Annals of Clinical and Translational Neurology, 2019, 6(11): 2186-96.\u003c/li\u003e\n\u003cli\u003e Binding L P, Dasgupta D, Giampiccolo D, et al. Structure and function of language networks in temporal lobe epilepsy [J]. Epilepsia, 2022, 63(5): 1025-40.\u003c/li\u003e\n\u003cli\u003e Seghier M L. The Angular Gyrus [J]. The Neuroscientist, 2012, 19(1): 43-61.\u003c/li\u003e\n\u003cli\u003e Jansen A, Fl\u0026ouml;el A, Van Randenborgh J, et al. Crossed cerebro\u0026ndash;cerebellar language dominance [J]. Human Brain Mapping, 2004, 24(3): 165-72.\u003c/li\u003e\n\u003cli\u003e Ridley B G Y, Rousseau C, Wirsich J, et al. Nodal approach reveals differential impact of lateralized focal epilepsies on hub reorganization [J]. NeuroImage, 2015, 118: 39-48.\u003c/li\u003e\n\u003cli\u003e Engel J, Jr, Thompson P M, et al. Connectomics and epilepsy [J]. Current Opinion in Neurology, 2013, 26(2): 186-94.\u003c/li\u003e\n\u003cli\u003e Royer J, Bernhardt B C, Larivi\u0026egrave;re S, et al. Epilepsy and brain network hubs [J]. Epilepsia, 2022, 63(3): 537-50.\u003c/li\u003e\n\u003cli\u003e de Bode S, Chanturidze M, Mathern G W, et al. Literacy after cerebral hemispherectomy: Can the isolated right hemisphere read? [J]. Epilepsy \u0026amp; Behavior, 2015, 45: 248-53.\u003c/li\u003e\n\u003cli\u003e Englot D J, Konrad P E, Morgan V L. Regional and global connectivity disturbances in focal epilepsy, related neurocognitive sequelae, and potential mechanistic underpinnings [J]. Epilepsia, 2016, 57(10): 1546-57.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Temporal lobe epilepsy, Cerebellum, Language impairment, Functional connectivity, Resting-state functional magnetic resonance imaging","lastPublishedDoi":"10.21203/rs.3.rs-5397184/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5397184/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eSince epilepsy is associated with different levels of cerebral dysfunction, there may be a recombination of language circuits in the course of epilepsy. The cerebellum is part of the whole brain language network. We explored the differences in speech impairment patterns in patients with TLE and different hemiencephalic attacks from the perspective of the cerebellum.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eFifty-eight patients with TLE and 30 healthy controls were recruited. including 28 patients with left temporal lobe epilepsy (LTLE) and 30 patients with right temporal lobe epilepsy (RTLE). The resting state functional connection method was used to investigate the effects of lateralization and cerebellar laterality on language function in patients with TLE. The differences in functional connectivity (FC) in the whole cerebellar cortex were compared between the three groups.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe FC analysis of the LTLE, RTLE, and HC groups showed significant differences between the three groups. Compared with the HC group, FC was decreased from the Cerebelum_Crus2_R to the right frontal cortex, from the Cerebelum_7_L to the right frontal cortex in both LTLE and RTLE groups. Compared with the LTLE group, FC was decreased from the Cerebelum_3_R to the left frontal pole, left inferior frontal gyrus, and left frontoorbital cortex in the RTLE group. Compared with the HC group, FC in the RTLE group was decreased between the Cerebelum 9L and right medial superior frontal gyrus and right dorsolateral superior frontal gyrus; between Cerebelum 9R and right medial superior frontal gyrus and left dorsolateral superior frontal gyrus; between Vermis9 and left posterior parietal lobe, between Vermis10 and right angular gyrus; between left middle temporal gyrus and language network; between right middle temporal gyrus and language network.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eIn the brain regions related to language, patients with RTLE had stronger left hemispheric activation than patients with LTLE. At the node level, the RTLE group had greater language central connection disorder than the HC group. Cerebellar-cerebral FC has different connectivity patterns between LTLE and RTLE groups. Cerebellar injury of TLE may lead to functional reorganization and transfer of language dominance to homologous regions in the other hemisphere.\u003c/p\u003e","manuscriptTitle":"Effect and mechanism of lateralization of cerebellar-cerebellar network abnormalities on language in patients with unilateral temporal lobe epilepsy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-18 08:05:43","doi":"10.21203/rs.3.rs-5397184/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"cf8c0c5b-6dcb-45ae-aeb8-481c1a3cb204","owner":[],"postedDate":"December 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-13T12:24:51+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-18 08:05:43","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5397184","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5397184","identity":"rs-5397184","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}