Assessing brain activity in patients with disorder of consciousness using the amplitude of low-frequency fluctuations and regional homogeneity derived from resting-state functional magnetic resonance images

Assessing brain activity in patients with disorder of consciousness using the amplitude of low-frequency fluctuations and regional homogeneity derived from resting-state functional magnetic resonance images | 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 Assessing brain activity in patients with disorder of consciousness using the amplitude of low-frequency fluctuations and regional homogeneity derived from resting-state functional magnetic resonance images Xuewei Qin, Xuanling Chen, Lan Yao, hongchuan niu, Shengpei Wang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4614073/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 Disorder of consciousness (DoC) is an impaired state of consciousness. This study used the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) measures obtained from resting-state functional magnetic resonance imaging (rs-fMRI) to observe neuronal activity changes in patients with DoC from various injuries for prognostic predictions. Methods This study included six patients with traumatic brain injury (TBI)-induced DoC and six patients with cerebrovascular disease (CVD)-induced DoC. Images were processed using Data Processing Assistant for rs-fMRI software to obtain the ALFF and ReHo values. Results The ALFF values were lower in the TBI group than in the CVD (i.e., control) group for the Precuneus_R, Superior frontal gyrus_R, Middle frontal gyrus, Middle occipital gyrus, and Hippocampus_R but higher for the bilateral insula, Postcentral gyrus_L, right moment gyrus, Superior parietal gyrus_L, and Inferior temporal gyrus_L. The ReHo values were higher in the TBI group than in the CVD group for the Precental gyrus_L and Postcentral gyrus_L, Middle temporal gyrus_R, right superior temporal gyrus, Superior temporal gyrus_R, Superior parietal gyrus_L, Superior frontal gyrus_R, and Inferior frontal gyrus)_L but lower for the Insula_R, Postcentral gyrus_R, Inferior frontal gyrus, Orbital part_L, straight gyrus, and Anterior cingulate_L. Consciousness improved in three patients with CVD DoC and one with TBI DoC. Conclusion ALFF and ReHo enhancements in the precuneus and frontal lobes on rs-fMRI might suggest improved consciousness for patients with CVD and TBI DoC. resting-state functional MRI amplitude of low-frequency fluctuations regional homogeneity Disorder of consciousness Injury type Anterior cuneate lobe Frontal lobe Figures Figure 1 Figure 2 Figure 3 1. Introduction A disorder of consciousness (DoC) is an altered state of consciousness in which the patient has an impaired interaction with the environment [ 1 , 2 ] . Various injuries cause DoC in adults, but traumatic brain injuries (TBIs), intracerebral and subarachnoid hemorrhages, and hypoxic-ischemic encephalopathy are the most common [ 3 – 5 ] . Several studies have reported medical and surgical interventions for treating patients in a vegetative state (VS) and minimally conscious state (MCS). These include neuromodulation techniques, which have become the mainstream techniques for wake-promoting therapy for patients in a VS, such as deep brain stimulation [ 6 , 7 ] and spinal cord stimulation (SCS) [ 8 ] . Notably, SCS is also an effective brain intervention technique for patients in an MCS [ 8 , 9 ] . Two primary types of DoCs are TBI-induced and cerebrovascular disease (CVD)-induced DoC. Diffuse axonal injury (DAI) is the result of extensive damage to long axons of the brain caused by TBI; it results from the rapid acceleration and deceleration of axons and is sometimes accompanied by delayed axonal disconnection, which can result in DoC [ 10 ] . Usually, a basilar artery stroke causes CVD DoC, which destroys the thalamus and upper brainstem [ 11 , 12 ] . Patients with DoC from TBI have a better prognosis than those without TBI [ 13 ] , except they have a low probability of awakening induced by ischemic hypoxic encephalopathy [ 14 , 15 ] . Furthermore, those with TBI DoC have a better prognosis than those with CVD DoC [ 4 , 16 , 17 ] . In studies of TBI-induced DoC, 38% and 78% of patients regained (minimal) consciousness after 3 and 12 months, respectively [ 18 ] , but only 17% of patients with CVD DoC regained consciousness 8 months after the injury [ 18 ] . Clinical behavioral observations and evaluations are one of the primary diagnostic methods at present, but they are subjective based on the evaluator. However, resting-state functional magnetic resonance imaging (rs-fMRI) for exploring the neural mechanisms of nervous system diseases is becoming increasingly popular. Calculating the vibration amplitude of the blood oxygenation level-dependent (BOLD) signal relative to the baseline results in the amplitude of low-frequency fluctuations (ALFF), which reflects the level of spontaneous activity in each voxel of the brain and is proportional to the intensity of regional neural activity [ 19 ] . To analyze regional homogeneity (ReHo), Kendall’s coefficient concordance (KCC) is used to assess the consistency of an integral element with its neighbors, reflecting the synchronization of whole brain voxels in the functional activity state of local brain regions [ 20 , 21 ] . The higher the ReHo value, the higher the consistency and centrality of regional brain activity [ 22 ] . Determining the state of consciousness and recovery potential of patients with acquired brain injury and accurately predicting whether patients will regain consciousness and function independently is critical. Thus, this study used ALFF and ReHo values calculated from rs-fMRI to investigate the manifestations of patients with DoC of different etiologies before starting SCS implantation, aiming to provide a diagnostic and treatment reference. 2. Methods 2.1 Patient selection The Peking University International Hospital’s ethics committee authorized the study, which conformed to the Declaration of Helsinki. All participants provided written informed consent before entering the study. This study enrolled 16 patients with DoC in the Department of Neurosurgery at Peking University International Hospital from January 2020 to March 2021. rs-fMRI scans were performed on all patients before SCS implantation surgery for awakening treatment, and they were assessed using the revised coma recovery scale (CRS-R) in our hospital’s rehabilitation department. The patients had no contraindications to MRI scanning and were not sedated or anesthetized before the procedure. The same senior neurosurgeon trained and qualified in the CRS-R evaluated the patients at discharge or when they were transferred to another hospital, Fig. 1 2.2 Inclusion and exclusion criteria Male and female patients, aged 18–70 years, scheduled to undergo SCS implantation were included. Additionally, the patients did not receive central sedative medications within 24 hours before the rs-fMRI scan. Patients with single or multiple organ failure, severe coagulation dysfunction, and death within 3 months after surgery were excluded. 2.3 Data acquisition The technician positioned the patient on their back on an MRI scanning bed and then used a foam pad inside a coil to secure their head and prevent movement. fMRI scanning was performed using a 3.0 T MRI scanner (Siemens Verio Dot 3.0 T, Munich, Germany) and eight phase-sensitivity coding head coils. The structural image parameters were: time of repetition (TR) = 2200 ms, time of echo (TE) = 3.25 ms, inversion time = 900 ms, flip angle (FA) = 9°, field of view (FOV) = 250 × 250 mm, matrix = 256 × 256, 192 layers, and thickness = 1.0 mm, no spacing. A gradient echo plane echo sequence imaging technique was used for functional imaging with TR = 2220 ms, TE = 30 ms, FA = 90°, FOV = 192 × 192mm, and matrix size = 64 × 64. The functional image was scanned in the same orientation as the structural image with 32-time points, and a total of 540 s was collected. Data preprocessing was performed by converting the DICOM format to a NIFTI format, which involves discarding the initial 10-time point signals to prevent interference from the non-equilibrium magnetization effect. It also included time level and head motion correction (rejection criteria: translation > 3 mm, rotation > 3°). The operational picture was aligned with the standard Montreal Neurological Institute space through segmentation parameters, and the voxel dimensions were adjusted to a volume of 3 × 3 × 3 mm 3 . The 4-mm half-height and full-width Gaussian check image was used for spatial smoothing. A Band-pass filter (0.01–0.08 Hz) was used for filtering. The effects of global, 24 head motion, cerebrospinal fluid, and white matter signals were removed by the linear regression method. 2.4 Data preprocessing 2.4.1 ALFF analysis Before the ALFF calculation, the data underwent initial smoothing with half-height and 6-mm width isotropic Gaussian filter images for spatial smoothing. Each voxel’s time series was transformed into the frequency domain using a fast Fourier transform to derive the power spectrum, followed by calculating the square root of the power spectrum for each frequency. The ALFF value was the average square root obtained on the filter frequency band of 0.01–0.1 Hz of each voxel. Next, the ALFF value for each voxel was computed by subtracting the average value of all brain voxels and then dividing by the standard deviation of the entire brain to determine the standardized ALFF value for each voxel. 2.4.2 ReHo analysis Before the ReHo calculation, the preprocessed data was filtered for 0.01–0.08 Hz. Data Processing Assistant for rs-fMRI (i.e., DPARSF) software was utilized to conduct the ReHo analysis, specifically employing the KCC to assess the correlation between the time series of individual voxels and their surrounding neighbors (26 adjacent voxels). The whole brain ReHo image of the subject was obtained by calculating the KCC value of the whole brain voxel. The ReHo values are standardized for statistical comparisons using Z-scores, meaning each voxel’s ReHo value was adjusted by subtracting the average voxel value of the entire brain and then dividing by the standard deviation of the entire brain. To enhance the signal-to-noise ratio, isotropic Gaussian check images with a 6-mm height and width were employed for spatial smoothing. 2.5 Statistical analyses SPSS 26.0 software (IBM Corp., Armonk, NY, USA) was used to analyze the patients’ demographic and clinical data. The Shapiro–Wilk test was utilized to assess the normal distribution of continuous numeric variables, Continuous (quantitative) data were presented as median (25% percentile, 75% percentile), and comparisons between groups were performed using the Wilcox test. Fisher’s exact or chi-square tests were used to compare categorical variables. P -values of < 0.05 were considered statistically significant. 3. Results 3.1 Patients demographics sixteen patients with DoC were screened for participation in the study. Three patients were excluded due to excessive head movements during the rs-fMRI scan (Rejection criteria: translation > 3mm, rotation > 3°) and poor image quality. One patient with ischemic and hypoxic DoC was excluded as it was the only case. Thus, seven patients with DoC were included and classified with TBI DoC (n = 6) or CVD DoC (n = 6; control group) depending on the cause of the injury. Tables 1 and 2 present general data and comparisons for the included patients. Table 1 General patient characteristics Case Sex (M/F) Age (years) Etiology Course of disease (m) Preoperative 3 months after surgery Consciousness state CRS-R total score and sub-scores* (A, V, M, OM, C, A r) Consciousness state CRS-R total score and sub-scores* (A, V, M, OM, C, A r) 1 M 50 ~ 60 TBI 3 VS 2 (0, 0, 1, 1, 0, 0) VS 4 (1, 0, 2, 1, 0, 0) 2 M 10 ~ 20 CVD 4 MCS+ 10 (3, 2, 1, 2, 0, 2) EMCS 23 (4, 5, 6, 3, 2, 3) 3 F 40 ~ 50 TBI 20 VS 7 (1, 1, 2, 1, 0, 2) VS 8 (1, 2, 2, 1, 0, 2) 4 M 30 ~ 40 TBI 16 MCS– 8 (1, 3, 1, 1, 0, 2) MCS+ 10 (3, 3, 1, 1, 0, 2) 5 F 50 ~ 60 CVD 6 MCS– 11 (2, 3, 3, 1, 0, 2) MCS+ 12 (3, 3, 3, 1, 0, 2) 6 M 50 ~ 60 CVD 15 MCS– 8 (1, 3, 1, 1, 0, 2) MCS+ 18 (4, 5, 5, 1, 1, 2) 7 F 40 ~ 50 CVD 12 VS 7 (1, 2, 2, 0, 0, 2) VS 8 (1, 2, 2, 1, 0, 2) 8 M 30 ~ 40 CVD 3 MCS+ 15(3,4,5,1,0,2) MCS+ 15(3,4,5,1,0,2) 9 M 40 ~ 50 TBI 6 MCS- 9(2,2,2,1,0,2,) MCS- 9(2,2,2,1,0,2) 10 F 30 ~ 40 TBI 6 VS 7(1,1,2,1,0,2) VS 7(1,1,2,1,0,2) 11 M 50 ~ 60 CVD 3 VS 7(1,1,2,1,0,2) VS 7(1,1,2,1,0,2) 12 M 50 ~ 60 TBI 4 VS 7(1,1,2,1,0,2) VS 7(1,1,2,1,0,2) *CRS-R total score and subscales, A, Auditory; V, Visual; M, Motor; OM, Oral Motor; C, Communication; Ar, Awake.Abbreviations: CRS-R: Revised coma recovery scale; CVD: cerebrovascular disease; EMCS: Emerging from minimally conscious state; MCS: Minimally conscious state; TBI: Traumatic brain injury; VS: Vegetative state. Table 2 Comparison of general data between the two groups category TBI group(n = 6) CVD group(n = 6) t/z P Sex Male 4 4 1.0 Female 2 2 Age 46.67 ± 11.34 44.33 ± 14.87 0.306 0.766 Etiology 6(4.5,13.5) 5(3.25,10.5) 0.732 0.464 3.2 ALFF results ALFF values were lower in the TBI group than in the CVD group for the Precuneus_R, Superior frontal gyrus_R, Middle frontal gyrus, Superior occipital gyrus_R, Middle occipital gyrus, and Hippocampus_R. However, they were higher in the bilateral Insula, Postcentral gyrus_L, Rectangular gyrus_R, Superior parietal gyrus_L, Inferior temporal gyrus_L, and brain stem (Table 3, Fig. 2 ). Table 3. ALFF value changes between patients with traumatic brain injuries DoC versus cerebrovascular disease DoC in various brain regions ALFF value change Encephalic region MNI space coordinates Voxel number T-value of the extreme point X Y Z Increase Postcentral_L –33 –36 66 29 5.1616 Calcarine_R 21 –48 6 27 5.9483 Right Brainstem 3 –3 –18 25 6.0865 Parietal_Sup_L –21 –54 69 59 6.3494 Thalamus_R 18 -21 3 97 9.0081 Temporal_Inf_L –33 –13 –24 33 9.8776 Thalamus_L 0 –18 18 255 12.8166 Decrease Precuneus_R 0 –48 60 29 –11.0867 Cingulum_Ant_L 0 48 3 162 –9.4272 Frontal_Sup_Orb_L –9 30 –21 25 –8.5593 Occipital_Sup_R 21 –102 3 32 –7.8661 Frontal_Sup_R 21 63 6 20 –6.651 Rectus_R 9 18 –27 21 –6.1817 Frontal_Mid_Orb_R 24 39 –15 20 –5.4361 Occipital_Mid_R 39 –90 18 42 –5.2129 Frontal_Sup_Orb_R 15 54 –15 31 –5.0801 Hippocampus_R 15 –3 –15 22 –5.0254 Frontal_Sup_Medial_L 0 57 33 66 –4.8583 Abbreviations: ALFF: Amplitude of low-frequency fluctuations; MNI: Montreal Neurological Institute. 3.3 ReHo results The ReHo values were higher in the TBI group than in the CVD group for the Precental gyrus_L, Postcentral gyrus_L, Temporal pole: middle temporal gyrus_R, Superior parietal gyrus_L, Superior frontal gyrus_R, Superior temporal gyrus_R, Inferior frontal gyrus)_L and Middle occipital gyrus_L; they were lower for the Anterior cingulate_L, Middle frontal gyrus_R, Insula_R, Postcentral gyrus_R, Inferior frontal gyrus, Orbital part_L, Gyrus rectus and Hippocampus_R (Table 4, Figure 3). Table 4 ReHo value changes between patients with traumatic brain injuries DoC versus cerebrovascular disease DoC in various brain regions ReHo value change Encephalic region MNI space coordinates Voxel numbers T-value of the extreme point X Y Z Increase Precentral_L –39 0 63 33 4.6316 Temporal_Pole_Mid_R 36 6 –30 20 5.2712 Postcentral_L –30 –36 57 46 5.6218 Parietal_Sup_L –18 –60 66 30 5.7222 Frontal_Sup_R 15 51 18 40 7.4875 Temporal_Sup_R 60 –39 12 20 8.4648 Lingual_R 24 –87 –12 23 8.9563 Frontal_Inf_Oper_L –45 12 21 20 11.2372 Middle Occipital Gyrus L –33 –84 –3 22 11.8628 Decrease Rectus_L -6 30 –27 27 –10.1637 Frontal_Inf_Orb_L –39 36 –9 28 –8.1495 Frontal_Mid_R 39 42 36 21 –7.4918 Insula_R (aal) 27 24 0 65 –7.4756 Cingulum_Ant_L –6 42 –3 37 –6.2721 Postcentral_R –57 –13 30 27 –4.4405 Middle Frontal Gyrus R 39 27 51 20 –4.3964 Abbreviations: MNI: Montreal Neurological Institute; ReHo: Regional homogeneity. 4. Discussion When the BOLD signal changes, the ALFF value indirectly reflects the spontaneous activation of the brain, which can indicate brain abnormalities at rest [19,23,24] . By increasing the ALFF, neurons in the corresponding brain region are more likely to be activated spontaneously, and activating this functional region may compensate for certain cognitive function impairments. A decreased ALFF value indicates that the intensity of the spontaneous activity of neurons in corresponding brain regions decreased, meaning that a neural activity decrease in these brain regions may be related to the loss of corresponding cognitive function. Thus, the ALFF value can be used to probe the basic brain activity of diseases. ReHo applies the KCC to assess the resemblance between the temporal patterns of a specific voxel to those of adjacent voxels in spatial proximity, illustrating the state of spontaneous brain activity regions with notable synchronization features, serving as a crucial measure to determine abnormal neuronal activity [20,25] . Changes in ReHo values indicate either heightened or diminished spontaneous neuronal activity in the specific brain region. ALFF and ReHo values are frequently used for investigating brain functional activities through the lens of functional specialization, offering distinct benefits in identifying brain regions that exhibit sustained activity in the resting state and providing a deeper insight into the alterations in brain activity among patients with DoC from varying forms of trauma. In this study, activated brain regions with elevated ALFF values in the TBI group included the bilateral insula, Postcentral gyrus_L, right torque-like gyrus, Superior parietal gyrus_L, Inferior temporal gyrus_L, and brain stem. In contrast, ALFF decreased in the anterior cuneiform, right superior frontal, middle frontal, right occipital gyri, and right hippocampi. The insula and Postcentral gyrus primarily handle sensation, temperature, language, and place perception [26,27] . However, evidence suggests that the precuneus, one of the most active cortical regions in the default mode network [28] , is inactivated in altered consciousness. The precuneus is believed to be a central component in functional networks involved in consciousness owing to its extensive connections to the cortices and subcortices. Many metabolic and structural cascades are associated with precuneus-related diseases as it is one of the brain’s most tightly connected central regions. For patients with DoC who recover consciousness, the precuneus is among the earliest brain areas to regain activity, and the more pronounced the decline in precuneus activity, the deeper the neurological disorder. Laureys et al. [29] reported that the posterior medial cortex and the thalamus had a different functional relationship during the VS, but it returned to a near-normal level once the patient regained consciousness. The anterior cuneus and posterior cingulate cortex also appear to be brain regions that distinguish patients in an MSC from those in a VS [34] . The medial frontal gyrus is an important part of the dorsolateral prefrontal lobe, and a component of this system participates in cognitive formation, emotional regulation, working memory, behavioral decision-making, attention regulation, abstract reasoning, behavioral inhibition, and pain inhibition [30,31] . In the frontal lobe, which is closely linked to cognitive and memory functions, decreased ALFF values may indicate that the brain is no longer functioning correctly [32] . Assessing clinical symptoms and cognitive dysfunction is also possible using ReHo values [33] . In this study, the ReHo values were higher in the TBI group than in the CVD group for the Precental gyrus_L and Postcentral gyrus, Middle temporal gyrus_R, Superior parietal gyrus_L, Superior frontal gyrus_R, right superior temporal gyrus, Superior temporal gyrus_R, and Inferior frontal gyrus, Orbital part_L, but they were lower for the Postcentral gyrus_R, right posterior superior frontal gyrus, Inferior frontal gyrus, Orbital part_L, and orbital and straight gyrus. The medial temporal gyrus performs language-related tasks, such as word understanding and semantic cognition, which receive input from the occipital lobe [34] . The brain’s language network has two key nodes: the middle temporal gyrus and the inferior frontal gyrus [36,36] . The Superior frontal gyrus contributes to motor control, working memory, resting state, cognitive control, and resting state information processing [34] . As an important part of the limbic system, the cingulate gyrus usually receives bottom-up emotional feedback information from the limbic system and then projects it to the higher-order cognitive control system (such as the area of the prefrontal cortex) through extensive connections for top-down cognitive control, mainly involved in the emotional motivation of pain perception and cognitive attention [37] . Finally, the medial frontal gyrus is an important part of the dorsolateral prefrontal lobe, involved in cognitive formation, emotional regulation, working memory, behavioral decision-making, attention regulation, abstract reasoning, behavioral inhibition, and pain inhibition. [30,31] . In this study, ALFF and ReHo values decreased in the TBI group compared to the CVD (control) group in various brain regions. As the brain’s higher attention center, the Superior frontal gyrus plays a key role in cognitive functions. A decrease in ALFF in these areas may indicate reduced brain function. Zhou et al [38] used ALFF at 0.01-0.08 Hz to detect thalamic and cortical damage in patients with traumatic brain injury and found that the thalamus and frontotemporal lobe had lower ALFF values. Depending on the etiology, shear or penetrating mechanical injuries in patients with traumatic brain injury are usually the result of acute, intense external forces that lead to skull fractures, intracranial hemorrhage, and more extensive injuries [39] . Vessel stenosis in patients with CVD is a slow process and is confined to specific vasculature-supplied brain regions, which to a certain extent still provides an opportunity for reorganization of the cerebral network. Three months after implantation of the SCS, one patient in the TBI group and three patients in the CVD group had improved consciousness according to the CRS-R score. Furthermore, the ALFF and ReHo values in the anterior cuneiform and frontal lobes of the TBI group were lower than those in the CVD group. In contrast, the ALFF and ReHo values were elevated in the precuneus and frontal brain regions of the CVD group compared to the TBI group, which could explain the improved levels of consciousness. This study is subject to certain limitations. Primarily, the inclusion of only two DoC injury types and a relatively small sample size necessitates the conduct of large multicenter studies encompassing multiple injury types to enable a comprehensive evaluation of the impact of network connectivity on patient prognosis. In this study, DoC patients with cardiovascular disease were utilized as a control group. However, the inclusion of additional suitable control groups, such as normal participants, is essential to effectively observe differences in injury types and to determine treatment effects. Furthermore, this study is a retrospective study with information bias. To mitigate this, we have blinded the data collection and used objective criteria to obtain the information, thereby minimizing bias. Nevertheless, this study is the first to evaluate the performance of ALFF and ReHo in resting patients with cardiovascular disease using fMRI techniques. This study identified ALFF and ReHo enhancement in the precuneus and frontal lobes of patients with DoC, which might be the anatomical basis for possible improvements in consciousness. Routine preoperative rs-fMRI should be considered to improve awakening therapy recovery rates. Declarations Acknowledgments The authors thank Professor Zongsheng Xu for providing rs-fMRI data of DoC patients. Author Contributions We obtained the clinical data from XQ, XC, and HN. HN performed the follow-up analysis of the post-operative state and performed a neurological evaluation on SW. XQ and XC drafted the manuscript. The manuscript was critically revised by LY, JH, and XG for important intellectual content. XQ, XC, and SW performed the statistical analysis. LY, XG, and XL supervised the study. All authors approved the final draft. Funding This research was funded by STI2030-Major Projects +2021ZD0204300 Ethics approval and consent to participate By the Declaration of Helsinki, this study was approved by the Institutional Review Board (or Ethics Committee) of Peking University International Hospital (2022-KY-0023-01, 01/04/2022). for studies involving humans. Consent for publication Not applicable. 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J Clin Neurophysiol. 2017;34(4):300–6. 10.1097/WNP.0000000000000377 . Kropf E, Syan SK, Minuzzi L, et al. From anatomy to function: the role of the somatosensory cortex in emotional regulation. Braz J Psychiatry. 2019;41(3):261–9. 10.1590/1516-4446-2018-0183 . Tsai YH, Yuan R, Huang YC, et al. Disruption of brain connectivity in acute stroke patients with early impairment in consciousness. Front Psychol. 2014;4:956. 10.3389/fpsyg.2013.00956 . Laureys S, Owen AM, Schiff ND. Brain function in coma, vegetative state, and related disorders. Lancet Neurol. 2004;3(9):537–46. 10.1016/S1474-4422(04)00852-X . Matsuda N, Kobayashi S, Ugawa Y. Rinsho Shinkeigaku. 2018;58(12):756–60. 10.5692/clinicalneurol.cn-001182 . von Clemm C, Dreßing H. Diebstahl als Pramipexol-assoziierte Impulskontrollstörung – Ein Fallbericht aus der Schuldfähigkeitsbegutachtung [Stealing as an Impulse Control Disorder Associated with Pramipexole - A Case Report from Forensic Psychiatric Practice]. Psychiatr Prax. 2017;44(3):172–4. 10.1055/s-0043-100024 . Xiong KL, Zhang JN, Zhang YL, et al. Brain functional connectivity and cognition in mild traumatic brain injury. Neuroradiology. 2016;58(7):733–9. 10.1007/s00234-016-1675-0 . Gao S, Ming Y, Wang J, et al. Enhanced Prefrontal Regional Homogeneity and Its Correlations With Cognitive Dysfunction/Psychopathology in Patients With First-Diagnosed and Drug-Naive Schizophrenia. Front Psychiatry. 2020;11:580570. 10.3389/fpsyt.2020.580570 . Briggs RG, Tanglay O, Dadario NB, et al. The Unique Fiber Anatomy of Middle Temporal Gyrus Default Mode Connectivity. Oper Neurosurg (Hagerstown). 2021;21(1):E8–14. 10.1093/ons/opab109 . Acheson DJ, Hagoort P. Stimulating the brain's language network: syntactic ambiguity resolution after TMS to the inferior frontal gyrus and middle temporal gyrus. J Cogn Neurosci. 2013;25(10):1664–77. 10.1162/jocn_a_00430 . Furlan M, Babcock L, Vallesi A. Decoding rule search domain in the left inferior frontal gyrus. PLoS ONE. 2018;13(3):e0194054. 10.1371/journal.pone.0194054 . Disner SG, Beevers CG, Haigh EA, et al. Neural mechanisms of the cognitive model of depression. Nat Rev Neurosci. 2011;12(8):467–77. 10.1038/nrn3027 . Zou QH, Zhu CZ, Yang Y, et al. An improved approach to detection of amplitude of low-frequency fluctuation (ALFF) for resting-state fMRI: fractional ALFF. J Neurosci Methods. 2008;172(1):137–41. 10.1016/j.jneumeth.2008.04.012 . Humble SS, Wilson LD, Wang L, et al. Prognosis of diffuse axonal injury with traumatic brain injury. J Trauma Acute Care Surg. 2018;85(1):155–9. 10.1097/TA.0000000000001852 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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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-4614073","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":317177575,"identity":"0529be36-0672-49c4-8672-e40a42d7913e","order_by":0,"name":"Xuewei Qin","email":"","orcid":"","institution":"Peking University International Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xuewei","middleName":"","lastName":"Qin","suffix":""},{"id":317177576,"identity":"1aa9dce9-b843-416e-a501-a17901ced69c","order_by":1,"name":"Xuanling Chen","email":"","orcid":"","institution":"Peking University International Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xuanling","middleName":"","lastName":"Chen","suffix":""},{"id":317177577,"identity":"7445b930-9f16-4906-9e74-e7e9cadbd55f","order_by":2,"name":"Lan Yao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2UlEQVRIie3LIQvCQBTA8TeErUzzDRH9CAdGxc9yx8CVsWIxGC49i2IVBD+H8caBK9NVwaLFpGA1KA4VMcgxm+H+4T0evB+AyfSfWRKgDQQszI9SMZOT7u9E5QTsYoQmSsrLIou8qY876Le4cFZST9Iui8fptlclfEghDbhwI6YnMqSyjFs+JxyJhYoL4lI9yY40vuL6RW5FyCakqoySzx5EFCDe5sBUDf2eN9ojYcugiW6oJ5XMj/cn7EQkCQ7kPGjVJk6qJw353Ow9be1/Xl18EpPJZDJ96w5aekvN97RalQAAAABJRU5ErkJggg==","orcid":"","institution":"Peking University International Hospital","correspondingAuthor":true,"prefix":"","firstName":"Lan","middleName":"","lastName":"Yao","suffix":""},{"id":317177578,"identity":"c2ab745c-1ea8-4cb4-8492-82c0739ff7cd","order_by":3,"name":"hongchuan niu","email":"","orcid":"","institution":"Peking University International Hospital","correspondingAuthor":false,"prefix":"","firstName":"hongchuan","middleName":"","lastName":"niu","suffix":""},{"id":317177579,"identity":"154a9442-d115-41aa-ae3c-3620226b1857","order_by":4,"name":"Shengpei Wang","email":"","orcid":"","institution":"Chinese Academy of Sciences","correspondingAuthor":false,"prefix":"","firstName":"Shengpei","middleName":"","lastName":"Wang","suffix":""},{"id":317177580,"identity":"edc2acab-0090-4fe0-b5bd-8ed762908454","order_by":5,"name":"Jianghong He","email":"","orcid":"","institution":"Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jianghong","middleName":"","lastName":"He","suffix":""},{"id":317177581,"identity":"e0319b34-6c8d-4c17-8220-2e2c2c54473a","order_by":6,"name":"Xiangyang Guo","email":"","orcid":"","institution":"Peking University Third Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xiangyang","middleName":"","lastName":"Guo","suffix":""},{"id":317177582,"identity":"c5d3508a-06de-4c30-b5c2-cf61cc58a0b6","order_by":7,"name":"Xiaoli Li","email":"","orcid":"","institution":"Beijing Normal University","correspondingAuthor":false,"prefix":"","firstName":"Xiaoli","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2024-06-21 00:08:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4614073/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4614073/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":60610269,"identity":"a5e32ea2-3aab-4006-bac6-05c15bab39e7","added_by":"auto","created_at":"2024-07-18 18:25:51","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":35217,"visible":true,"origin":"","legend":"\u003cp\u003eflow chart\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-4614073/v1/1835a62fb6082321a3512ac9.png"},{"id":60610270,"identity":"7138fa7b-2568-44ba-ac68-89743a4e1eab","added_by":"auto","created_at":"2024-07-18 18:25:51","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":741481,"visible":true,"origin":"","legend":"\u003cp\u003eRegions of the brain with increased (red) and decreased (blue) amplitude of low-frequency fluctuation values in the TBI group versus the control group. (A) Shows elevated ALFF values in the bilateral Insula, Postcentral gyrus_L, Rectangular gyrus_R, Superior parietal gyrus_L, Inferior temporal gyrus_L and brain stem brain regions ; (B) Shows decreased ALFF values in the Precuneus_R, Superior frontal gyrus_R, Middle frontal gyrus, Superior occipital gyrus_R, Middle occipital gyrus, and Hippocampus_R brain regions.\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-4614073/v1/f670556d815b2cbdb1286b12.png"},{"id":60610268,"identity":"5b9c68b9-0855-4448-ba65-e35a35c025a3","added_by":"auto","created_at":"2024-07-18 18:25:51","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":826612,"visible":true,"origin":"","legend":"\u003cp\u003eRegions of the brain with increased (red) and decreased (blue) regional homogeneity values in the TBI group versus the control group. (A) Shows elevated ALFF values in the Precental gyrus_L, Postcentral gyrus_L, Temporal pole: middle temporal gyrus_R, Superior parietal gyrus_L, Superior frontal gyrus_R, Superior temporal gyrus_R, Inferior frontal gyrus)_L and Middle occipital gyrus_L ; (B) Shows decreased ALFF values in the Anterior cingulate_L, Middle frontal gyrus_R, Insula_R, Postcentral gyrus_R, Inferior frontal gyrus, Orbital part_L, Gyrus rectus, and Hippocampus_R brain regions.\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-4614073/v1/d6c7816591e3450d6a3ebe07.png"},{"id":68897378,"identity":"82a428a0-6b82-4ea5-83a1-0fc46ca5549d","added_by":"auto","created_at":"2024-11-13 09:02:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2883081,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4614073/v1/aa7e3cef-0185-4b03-b316-f3f5ca070448.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Assessing brain activity in patients with disorder of consciousness using the amplitude of low-frequency fluctuations and regional homogeneity derived from resting-state functional magnetic resonance images","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eA disorder of consciousness (DoC) is an altered state of consciousness in which the patient has an impaired interaction with the environment \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Various injuries cause DoC in adults, but traumatic brain injuries (TBIs), intracerebral and subarachnoid hemorrhages, and hypoxic-ischemic encephalopathy are the most common \u003csup\u003e[\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSeveral studies have reported medical and surgical interventions for treating patients in a vegetative state (VS) and minimally conscious state (MCS). These include neuromodulation techniques, which have become the mainstream techniques for wake-promoting therapy for patients in a VS, such as deep brain stimulation \u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e and spinal cord stimulation (SCS) \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. Notably, SCS is also an effective brain intervention technique for patients in an MCS \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eTwo primary types of DoCs are TBI-induced and cerebrovascular disease (CVD)-induced DoC. Diffuse axonal injury (DAI) is the result of extensive damage to long axons of the brain caused by TBI; it results from the rapid acceleration and deceleration of axons and is sometimes accompanied by delayed axonal disconnection, which can result in DoC \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. Usually, a basilar artery stroke causes CVD DoC, which destroys the thalamus and upper brainstem \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. Patients with DoC from TBI have a better prognosis than those without TBI \u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e, except they have a low probability of awakening induced by ischemic hypoxic encephalopathy \u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. Furthermore, those with TBI DoC have a better prognosis than those with CVD DoC \u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. In studies of TBI-induced DoC, 38% and 78% of patients regained (minimal) consciousness after 3 and 12 months, respectively \u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e, but only 17% of patients with CVD DoC regained consciousness 8 months after the injury \u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eClinical behavioral observations and evaluations are one of the primary diagnostic methods at present, but they are subjective based on the evaluator. However, resting-state functional magnetic resonance imaging (rs-fMRI) for exploring the neural mechanisms of nervous system diseases is becoming increasingly popular. Calculating the vibration amplitude of the blood oxygenation level-dependent (BOLD) signal relative to the baseline results in the amplitude of low-frequency fluctuations (ALFF), which reflects the level of spontaneous activity in each voxel of the brain and is proportional to the intensity of regional neural activity \u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e. To analyze regional homogeneity (ReHo), Kendall\u0026rsquo;s coefficient concordance (KCC) is used to assess the consistency of an integral element with its neighbors, reflecting the synchronization of whole brain voxels in the functional activity state of local brain regions \u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. The higher the ReHo value, the higher the consistency and centrality of regional brain activity \u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eDetermining the state of consciousness and recovery potential of patients with acquired brain injury and accurately predicting whether patients will regain consciousness and function independently is critical. Thus, this study used ALFF and ReHo values calculated from rs-fMRI to investigate the manifestations of patients with DoC of different etiologies before starting SCS implantation, aiming to provide a diagnostic and treatment reference.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Patient selection\u003c/h2\u003e \u003cp\u003e The Peking University International Hospital\u0026rsquo;s ethics committee authorized the study, which conformed to the Declaration of Helsinki. All participants provided written informed consent before entering the study.\u003c/p\u003e \u003cp\u003eThis study enrolled 16 patients with DoC in the Department of Neurosurgery at Peking University International Hospital from January 2020 to March 2021. rs-fMRI scans were performed on all patients before SCS implantation surgery for awakening treatment, and they were assessed using the revised coma recovery scale (CRS-R) in our hospital\u0026rsquo;s rehabilitation department. The patients had no contraindications to MRI scanning and were not sedated or anesthetized before the procedure. The same senior neurosurgeon trained and qualified in the CRS-R evaluated the patients at discharge or when they were transferred to another hospital, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003c/p\u003e\u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Inclusion and exclusion criteria\u003c/h2\u003e \u003cp\u003eMale and female patients, aged 18\u0026ndash;70 years, scheduled to undergo SCS implantation were included. Additionally, the patients did not receive central sedative medications within 24 hours before the rs-fMRI scan. Patients with single or multiple organ failure, severe coagulation dysfunction, and death within 3 months after surgery were excluded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Data acquisition\u003c/h2\u003e \u003cp\u003eThe technician positioned the patient on their back on an MRI scanning bed and then used a foam pad inside a coil to secure their head and prevent movement. fMRI scanning was performed using a 3.0 T MRI scanner (Siemens Verio Dot 3.0 T, Munich, Germany) and eight phase-sensitivity coding head coils. The structural image parameters were: time of repetition (TR)\u0026thinsp;=\u0026thinsp;2200 ms, time of echo (TE)\u0026thinsp;=\u0026thinsp;3.25 ms, inversion time\u0026thinsp;=\u0026thinsp;900 ms, flip angle (FA)\u0026thinsp;=\u0026thinsp;9\u0026deg;, field of view (FOV)\u0026thinsp;=\u0026thinsp;250 \u0026times; 250 mm, matrix\u0026thinsp;=\u0026thinsp;256 \u0026times; 256, 192 layers, and thickness\u0026thinsp;=\u0026thinsp;1.0 mm, no spacing. A gradient echo plane echo sequence imaging technique was used for functional imaging with TR\u0026thinsp;=\u0026thinsp;2220 ms, TE\u0026thinsp;=\u0026thinsp;30 ms, FA\u0026thinsp;=\u0026thinsp;90\u0026deg;, FOV\u0026thinsp;=\u0026thinsp;192 \u0026times; 192mm, and matrix size\u0026thinsp;=\u0026thinsp;64 \u0026times; 64. The functional image was scanned in the same orientation as the structural image with 32-time points, and a total of 540 s was collected.\u003c/p\u003e \u003cp\u003eData preprocessing was performed by converting the DICOM format to a NIFTI format, which involves discarding the initial 10-time point signals to prevent interference from the non-equilibrium magnetization effect. It also included time level and head motion correction (rejection criteria: translation\u0026thinsp;\u0026gt;\u0026thinsp;3 mm, rotation\u0026thinsp;\u0026gt;\u0026thinsp;3\u0026deg;). The operational picture was aligned with the standard Montreal Neurological Institute space through segmentation parameters, and the voxel dimensions were adjusted to a volume of 3 \u0026times; 3 \u0026times; 3 mm\u003csup\u003e3\u003c/sup\u003e. The 4-mm half-height and full-width Gaussian check image was used for spatial smoothing. A Band-pass filter (0.01\u0026ndash;0.08 Hz) was used for filtering. The effects of global, 24 head motion, cerebrospinal fluid, and white matter signals were removed by the linear regression method.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Data preprocessing\u003c/h2\u003e \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e \u003ch2\u003e2.4.1 ALFF analysis\u003c/h2\u003e \u003cp\u003eBefore the ALFF calculation, the data underwent initial smoothing with half-height and 6-mm width isotropic Gaussian filter images for spatial smoothing. Each voxel\u0026rsquo;s time series was transformed into the frequency domain using a fast Fourier transform to derive the power spectrum, followed by calculating the square root of the power spectrum for each frequency. The ALFF value was the average square root obtained on the filter frequency band of 0.01\u0026ndash;0.1 Hz of each voxel. Next, the ALFF value for each voxel was computed by subtracting the average value of all brain voxels and then dividing by the standard deviation of the entire brain to determine the standardized ALFF value for each voxel.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section3\"\u003e \u003ch2\u003e2.4.2 ReHo analysis\u003c/h2\u003e \u003cp\u003eBefore the ReHo calculation, the preprocessed data was filtered for 0.01\u0026ndash;0.08 Hz. Data Processing Assistant for rs-fMRI (i.e., DPARSF) software was utilized to conduct the ReHo analysis, specifically employing the KCC to assess the correlation between the time series of individual voxels and their surrounding neighbors (26 adjacent voxels). The whole brain ReHo image of the subject was obtained by calculating the KCC value of the whole brain voxel. The ReHo values are standardized for statistical comparisons using Z-scores, meaning each voxel\u0026rsquo;s ReHo value was adjusted by subtracting the average voxel value of the entire brain and then dividing by the standard deviation of the entire brain. To enhance the signal-to-noise ratio, isotropic Gaussian check images with a 6-mm height and width were employed for spatial smoothing.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Statistical analyses\u003c/h2\u003e \u003cp\u003eSPSS 26.0 software (IBM Corp., Armonk, NY, USA) was used to analyze the patients\u0026rsquo; demographic and clinical data. The Shapiro\u0026ndash;Wilk test was utilized to assess the normal distribution of continuous numeric variables, Continuous (quantitative) data were presented as median (25% percentile, 75% percentile), and comparisons between groups were performed using the Wilcox test. Fisher\u0026rsquo;s exact or chi-square tests were used to compare categorical variables. \u003cem\u003eP\u003c/em\u003e-values of \u0026lt;\u0026thinsp;0.05 were considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Patients demographics\u003c/h2\u003e \u003cp\u003esixteen patients with DoC were screened for participation in the study. Three patients were excluded due to excessive head movements during the rs-fMRI scan (Rejection criteria: translation\u0026thinsp;\u0026gt;\u0026thinsp;3mm, rotation\u0026thinsp;\u0026gt;\u0026thinsp;3\u0026deg;) and poor image quality. One patient with ischemic and hypoxic DoC was excluded as it was the only case. Thus, seven patients with DoC were included and classified with TBI DoC (n\u0026thinsp;=\u0026thinsp;6) or CVD DoC (n\u0026thinsp;=\u0026thinsp;6; control group) depending on the cause of the injury. Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e present general data and comparisons for the included patients.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eGeneral patient characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"11\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCase\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSex (M/F)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003cp\u003e(years)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eEtiology\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCourse of disease\u003c/p\u003e \u003cp\u003e(m)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c10\" namest=\"c6\"\u003e \u003cp\u003ePreoperative\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003e3 months after surgery\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eConsciousness state\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003eCRS-R total score and sub-scores*\u003c/p\u003e \u003cp\u003e(A, V, M, OM, C, A r)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eConsciousness state\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003eCRS-R total score and sub-scores*\u003c/p\u003e \u003cp\u003e(A, V, M, OM, C, A r)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50\u0026thinsp;~\u0026thinsp;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTBI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eVS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2 (0, 0, 1, 1, 0, 0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eVS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e4 (1, 0, 2, 1, 0, 0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u0026thinsp;~\u0026thinsp;20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCVD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMCS+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e10 (3, 2, 1, 2, 0, 2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eEMCS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e23 (4, 5, 6, 3, 2, 3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40\u0026thinsp;~\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTBI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eVS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7 (1, 1, 2, 1, 0, 2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eVS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e8 (1, 2, 2, 1, 0, 2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30\u0026thinsp;~\u0026thinsp;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTBI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMCS\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8 (1, 3, 1, 1, 0, 2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eMCS+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e10 (3, 3, 1, 1, 0, 2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50\u0026thinsp;~\u0026thinsp;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCVD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMCS\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e11 (2, 3, 3, 1, 0, 2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eMCS+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e12 (3, 3, 3, 1, 0, 2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50\u0026thinsp;~\u0026thinsp;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCVD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMCS\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8 (1, 3, 1, 1, 0, 2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eMCS+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e18 (4, 5, 5, 1, 1, 2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40\u0026thinsp;~\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCVD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eVS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7 (1, 2, 2, 0, 0, 2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eVS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e8 (1, 2, 2, 1, 0, 2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30\u0026thinsp;~\u0026thinsp;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCVD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMCS+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15(3,4,5,1,0,2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eMCS+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e15(3,4,5,1,0,2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40\u0026thinsp;~\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTBI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMCS-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9(2,2,2,1,0,2,)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eMCS-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e9(2,2,2,1,0,2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30\u0026thinsp;~\u0026thinsp;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTBI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eVS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7(1,1,2,1,0,2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eVS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e7(1,1,2,1,0,2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50\u0026thinsp;~\u0026thinsp;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCVD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eVS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7(1,1,2,1,0,2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eVS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e7(1,1,2,1,0,2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50\u0026thinsp;~\u0026thinsp;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTBI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eVS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7(1,1,2,1,0,2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eVS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e7(1,1,2,1,0,2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e*CRS-R total score and subscales, A, Auditory; V, Visual; M, Motor; OM, Oral Motor; C, Communication; Ar, Awake.Abbreviations: CRS-R: Revised coma recovery scale; CVD: cerebrovascular disease; EMCS: Emerging from minimally conscious state; MCS: Minimally conscious state; TBI: Traumatic brain injury; VS: Vegetative state.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of general data between the two groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecategory\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTBI group(n\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCVD group(n\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003et/z\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46.67\u0026thinsp;\u0026plusmn;\u0026thinsp;11.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44.33\u0026thinsp;\u0026plusmn;\u0026thinsp;14.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.306\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.766\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEtiology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(4.5,13.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5(3.25,10.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.732\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.464\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.2 ALFF results\u003c/h2\u003e \u003cp\u003eALFF values were lower in the TBI group than in the CVD group for the Precuneus_R, Superior frontal gyrus_R, Middle frontal gyrus, Superior occipital gyrus_R, Middle occipital gyrus, and Hippocampus_R. However, they were higher in the bilateral Insula, Postcentral gyrus_L, Rectangular gyrus_R, Superior parietal gyrus_L, Inferior temporal gyrus_L, and brain stem (Table\u0026nbsp;3, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e\u003cstrong\u003eTable 3.\u003c/strong\u003e ALFF value changes between patients with\u0026nbsp;traumatic brain injuries\u0026nbsp;DoC versus\u0026nbsp;cerebrovascular disease\u0026nbsp;DoC in various brain regions\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"728\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.15680880330124%\" rowspan=\"2\"\u003e\n \u003cp\u003eALFF\u0026nbsp;value change\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.944979367262725%\" rowspan=\"2\"\u003e\n \u003cp\u003eEncephalic region\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.822558459422282%\" colspan=\"3\"\u003e\n \u003cp\u003eMNI\u0026nbsp;space coordinates\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.480055020632737%\" rowspan=\"2\"\u003e\n \u003cp\u003eVoxel number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.595598349381017%\" rowspan=\"2\"\u003e\n \u003cp\u003eT-value of the extreme point\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.142857142857146%\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.081632653061224%\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.775510204081634%\"\u003e\n \u003cp\u003eZ\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.13186813186813%\" valign=\"top\"\u003e\n \u003cp\u003eIncrease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.917582417582416%\"\u003e\n \u003cp\u003ePostcentral_L\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.653846153846153%\"\u003e\n \u003cp\u003e\u0026ndash;33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.829670329670329%\"\u003e\n \u003cp\u003e\u0026ndash;36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.43956043956044%\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.461538461538462%\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.565934065934066%\"\u003e\n \u003cp\u003e5.1616\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.13186813186813%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.917582417582416%\"\u003e\n \u003cp\u003eCalcarine_R\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.653846153846153%\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.829670329670329%\"\u003e\n \u003cp\u003e\u0026ndash;48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.43956043956044%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.461538461538462%\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.565934065934066%\"\u003e\n \u003cp\u003e5.9483\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.13186813186813%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.917582417582416%\"\u003e\n \u003cp\u003eRight Brainstem\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.653846153846153%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.829670329670329%\"\u003e\n \u003cp\u003e\u0026ndash;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.43956043956044%\"\u003e\n \u003cp\u003e\u0026ndash;18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.461538461538462%\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.565934065934066%\"\u003e\n \u003cp\u003e6.0865\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.13186813186813%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.917582417582416%\"\u003e\n \u003cp\u003eParietal_Sup_L\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.653846153846153%\"\u003e\n \u003cp\u003e\u0026ndash;21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.829670329670329%\"\u003e\n \u003cp\u003e\u0026ndash;54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.43956043956044%\"\u003e\n \u003cp\u003e69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.461538461538462%\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.565934065934066%\"\u003e\n \u003cp\u003e6.3494\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.13186813186813%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.917582417582416%\"\u003e\n \u003cp\u003eThalamus_R\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.653846153846153%\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.829670329670329%\"\u003e\n \u003cp\u003e-21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.43956043956044%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.461538461538462%\"\u003e\n \u003cp\u003e97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.565934065934066%\"\u003e\n \u003cp\u003e9.0081\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.13186813186813%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.917582417582416%\"\u003e\n \u003cp\u003eTemporal_Inf_L\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.653846153846153%\"\u003e\n \u003cp\u003e\u0026ndash;33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.829670329670329%\"\u003e\n \u003cp\u003e\u0026ndash;13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.43956043956044%\"\u003e\n \u003cp\u003e\u0026ndash;24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.461538461538462%\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.565934065934066%\"\u003e\n \u003cp\u003e9.8776\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.13186813186813%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.917582417582416%\"\u003e\n \u003cp\u003eThalamus_L\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.653846153846153%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.829670329670329%\"\u003e\n \u003cp\u003e\u0026ndash;18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.43956043956044%\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.461538461538462%\"\u003e\n \u003cp\u003e255\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.565934065934066%\"\u003e\n \u003cp\u003e12.8166\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.13186813186813%\" valign=\"top\"\u003e\n \u003cp\u003eDecrease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.917582417582416%\"\u003e\n \u003cp\u003ePrecuneus_R\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.653846153846153%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.829670329670329%\"\u003e\n \u003cp\u003e\u0026ndash;48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.43956043956044%\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.461538461538462%\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.565934065934066%\"\u003e\n \u003cp\u003e\u0026ndash;11.0867\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.13186813186813%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.917582417582416%\"\u003e\n \u003cp\u003eCingulum_Ant_L\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.653846153846153%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.829670329670329%\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.43956043956044%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.461538461538462%\"\u003e\n \u003cp\u003e162\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.565934065934066%\"\u003e\n \u003cp\u003e\u0026ndash;9.4272\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.13186813186813%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.917582417582416%\"\u003e\n \u003cp\u003eFrontal_Sup_Orb_L\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.653846153846153%\"\u003e\n \u003cp\u003e\u0026ndash;9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.829670329670329%\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.43956043956044%\"\u003e\n \u003cp\u003e\u0026ndash;21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.461538461538462%\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.565934065934066%\"\u003e\n \u003cp\u003e\u0026ndash;8.5593\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.13186813186813%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.917582417582416%\"\u003e\n \u003cp\u003eOccipital_Sup_R\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.653846153846153%\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.829670329670329%\"\u003e\n \u003cp\u003e\u0026ndash;102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.43956043956044%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.461538461538462%\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.565934065934066%\"\u003e\n \u003cp\u003e\u0026ndash;7.8661\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.13186813186813%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.917582417582416%\"\u003e\n \u003cp\u003eFrontal_Sup_R\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.653846153846153%\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.829670329670329%\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.43956043956044%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.461538461538462%\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.565934065934066%\"\u003e\n \u003cp\u003e\u0026ndash;6.651\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.13186813186813%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.917582417582416%\"\u003e\n \u003cp\u003eRectus_R\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.653846153846153%\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.829670329670329%\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.43956043956044%\"\u003e\n \u003cp\u003e\u0026ndash;27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.461538461538462%\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.565934065934066%\"\u003e\n \u003cp\u003e\u0026ndash;6.1817\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.13186813186813%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.917582417582416%\"\u003e\n \u003cp\u003eFrontal_Mid_Orb_R\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.653846153846153%\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.829670329670329%\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.43956043956044%\"\u003e\n \u003cp\u003e\u0026ndash;15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.461538461538462%\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.565934065934066%\"\u003e\n \u003cp\u003e\u0026ndash;5.4361\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.13186813186813%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.917582417582416%\"\u003e\n \u003cp\u003eOccipital_Mid_R\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.653846153846153%\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.829670329670329%\"\u003e\n \u003cp\u003e\u0026ndash;90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.43956043956044%\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.461538461538462%\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.565934065934066%\"\u003e\n \u003cp\u003e\u0026ndash;5.2129\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.13186813186813%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.917582417582416%\"\u003e\n \u003cp\u003eFrontal_Sup_Orb_R\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.653846153846153%\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.829670329670329%\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.43956043956044%\"\u003e\n \u003cp\u003e\u0026ndash;15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.461538461538462%\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.565934065934066%\"\u003e\n \u003cp\u003e\u0026ndash;5.0801\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.13186813186813%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.917582417582416%\"\u003e\n \u003cp\u003eHippocampus_R\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.653846153846153%\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.829670329670329%\"\u003e\n \u003cp\u003e\u0026ndash;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.43956043956044%\"\u003e\n \u003cp\u003e\u0026ndash;15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.461538461538462%\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.565934065934066%\"\u003e\n \u003cp\u003e\u0026ndash;5.0254\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.13186813186813%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.917582417582416%\"\u003e\n \u003cp\u003eFrontal_Sup_Medial_L\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.653846153846153%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.829670329670329%\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.43956043956044%\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.461538461538462%\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.565934065934066%\"\u003e\n \u003cp\u003e\u0026ndash;4.8583\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\u003eAbbreviations: ALFF: Amplitude of low-frequency fluctuations; MNI: Montreal Neurological Institute.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.3 ReHo results\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe ReHo values were higher in the TBI group than in the CVD group for the Precental gyrus_L, Postcentral gyrus_L, Temporal pole: middle temporal gyrus_R, Superior parietal gyrus_L, Superior frontal gyrus_R, Superior temporal gyrus_R, Inferior frontal gyrus)_L and Middle occipital gyrus_L; they were lower for the Anterior cingulate_L, Middle frontal gyrus_R, Insula_R, Postcentral gyrus_R, Inferior frontal gyrus, Orbital part_L, Gyrus rectus and Hippocampus_R (Table 4, Figure 3).\u003c/p\u003e\n\u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eReHo value changes between patients with traumatic brain injuries DoC versus cerebrovascular disease DoC in various brain regions\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eReHo value change\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eEncephalic region\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003eMNI space coordinates\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVoxel numbers\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eT-value of the extreme point\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eY\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eZ\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIncrease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePrecentral_L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026ndash;39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.6316\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTemporal_Pole_Mid_R\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026ndash;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.2712\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePostcentral_L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026ndash;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026ndash;36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.6218\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eParietal_Sup_L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026ndash;18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026ndash;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.7222\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFrontal_Sup_R\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7.4875\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTemporal_Sup_R\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026ndash;39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8.4648\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLingual_R\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026ndash;87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026ndash;12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8.9563\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFrontal_Inf_Oper_L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026ndash;45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e11.2372\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMiddle Occipital Gyrus L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026ndash;33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026ndash;84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026ndash;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e11.8628\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDecrease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRectus_L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026ndash;27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026ndash;10.1637\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFrontal_Inf_Orb_L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026ndash;39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026ndash;9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026ndash;8.1495\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFrontal_Mid_R\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026ndash;7.4918\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInsula_R (aal)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026ndash;7.4756\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCingulum_Ant_L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026ndash;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026ndash;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026ndash;6.2721\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePostcentral_R\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026ndash;57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026ndash;13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026ndash;4.4405\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMiddle Frontal Gyrus R\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026ndash;4.3964\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eAbbreviations: MNI: Montreal Neurological Institute; ReHo: Regional homogeneity.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e "},{"header":"4. Discussion","content":"\u003cp\u003eWhen the BOLD signal changes, the ALFF value indirectly reflects the spontaneous activation of the brain, which can indicate brain abnormalities at rest \u003csup\u003e[19,23,24]\u003c/sup\u003e. By increasing the ALFF, neurons in the corresponding brain region are more likely to be activated spontaneously, and activating this functional region may compensate for certain cognitive function impairments. A decreased ALFF value indicates that the intensity of the spontaneous activity of neurons in corresponding brain regions decreased, meaning that a neural activity decrease in these brain regions may be related to the loss of corresponding cognitive function. Thus, the ALFF value can be used to probe the basic brain activity of diseases.\u003c/p\u003e\n\u003cp\u003eReHo applies the KCC to assess the resemblance between the temporal patterns of a specific voxel to those of adjacent voxels in spatial proximity, illustrating the state of spontaneous brain activity regions with notable synchronization features, serving as a crucial measure to determine abnormal neuronal activity \u003csup\u003e[20,25]\u003c/sup\u003e. Changes in ReHo values indicate either heightened or diminished spontaneous neuronal activity in the specific brain region.\u003c/p\u003e\n\u003cp\u003eALFF and ReHo values are frequently used for investigating brain functional activities through the lens of functional specialization, offering distinct benefits in identifying brain regions that exhibit sustained activity in the resting state and providing a deeper insight into the alterations in brain activity among patients with DoC from varying forms of trauma. In this study, activated brain regions with elevated ALFF values in the TBI group included the bilateral insula, Postcentral gyrus_L, right torque-like gyrus, Superior parietal gyrus_L, Inferior temporal gyrus_L, and brain stem. In contrast, ALFF decreased in the anterior cuneiform, right superior frontal, middle frontal, right occipital gyri, and right hippocampi. The insula and Postcentral gyrus primarily handle sensation, temperature, language, and place perception \u003csup\u003e[26,27]\u003c/sup\u003e. However, evidence suggests that the precuneus, one of the most active cortical regions in the default mode network \u003csup\u003e[28]\u003c/sup\u003e, is inactivated in altered consciousness. The precuneus is believed to be a central component in functional networks involved in consciousness owing to its extensive connections to the cortices and subcortices. Many metabolic and structural cascades are associated with precuneus-related diseases as it is one of the brain\u0026rsquo;s most tightly connected central regions. For patients with DoC who recover consciousness, the precuneus is among the earliest brain areas to regain activity, and the more pronounced the decline in precuneus activity, the deeper the neurological disorder. Laureys et al.\u003csup\u003e\u0026nbsp;[29]\u003c/sup\u003e reported that the posterior medial cortex and the thalamus had a different functional relationship during the VS, but it returned to a near-normal level once the patient regained consciousness. The anterior cuneus and posterior cingulate cortex also appear to be brain regions that distinguish patients in an MSC from those in a VS \u003csup\u003e[34]\u003c/sup\u003e. The medial frontal gyrus is an important part of the dorsolateral prefrontal lobe, and a component of this system participates in cognitive formation, emotional regulation, working memory, behavioral decision-making, attention regulation, abstract reasoning, behavioral inhibition, and pain inhibition \u003csup\u003e[30,31]\u003c/sup\u003e. In the frontal lobe, which is closely linked to cognitive and memory functions, decreased ALFF values may indicate that the brain is no longer functioning correctly \u003csup\u003e[32]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eAssessing clinical symptoms and cognitive dysfunction is also possible using ReHo values \u003csup\u003e[33]\u003c/sup\u003e. In this study, the ReHo values were higher in the TBI group than in the CVD group for the Precental gyrus_L and Postcentral gyrus, Middle temporal gyrus_R, Superior parietal gyrus_L, Superior frontal gyrus_R, right superior temporal gyrus, Superior temporal gyrus_R, and Inferior frontal gyrus, Orbital part_L, but they were lower for the Postcentral gyrus_R, right posterior superior frontal gyrus, Inferior frontal gyrus, Orbital part_L, and orbital and straight gyrus. The medial temporal gyrus performs language-related tasks, such as word understanding and semantic cognition, which receive input from the occipital lobe \u003csup\u003e[34]\u003c/sup\u003e. The brain\u0026rsquo;s language network has two key nodes: the middle temporal gyrus and the inferior frontal gyrus \u003csup\u003e[36,36]\u003c/sup\u003e. The Superior frontal gyrus contributes to motor control, working memory, resting state, cognitive control, and resting state information processing \u003csup\u003e[34]\u003c/sup\u003e. As an important part of the limbic system, the cingulate gyrus usually receives bottom-up emotional feedback information from the limbic system and then projects it to the higher-order cognitive control system (such as the area of the prefrontal cortex) through extensive connections for top-down cognitive control, mainly involved in the emotional motivation of pain perception and cognitive attention \u003csup\u003e[37]\u003c/sup\u003e. Finally, the medial frontal gyrus is an important part of the dorsolateral prefrontal lobe, involved in cognitive formation, emotional regulation, working memory, behavioral decision-making, attention regulation, abstract reasoning, behavioral inhibition, and pain inhibition. \u003csup\u003e[30,31]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eIn this study, ALFF and ReHo values decreased in the TBI group compared to the CVD (control) group in various brain regions. As the brain\u0026rsquo;s higher attention center, the Superior frontal gyrus plays a key role in cognitive functions. A decrease in ALFF in these areas may indicate reduced brain function. Zhou et al \u003csup\u003e[38]\u003c/sup\u003e used ALFF at 0.01-0.08 Hz to detect thalamic and cortical damage in patients with traumatic brain injury and found that the thalamus and frontotemporal lobe had lower ALFF values. Depending on the etiology, shear or penetrating mechanical injuries in patients with traumatic brain injury are usually the result of acute, intense external forces that lead to skull fractures, intracranial hemorrhage, and more extensive injuries \u003csup\u003e[39]\u003c/sup\u003e. Vessel stenosis in patients with CVD is a slow process and is confined to specific vasculature-supplied brain regions, which to a certain extent still provides an opportunity for reorganization of the cerebral network. Three months after implantation of the SCS, one patient in the TBI group and three patients in the CVD group had improved consciousness according to the CRS-R score. Furthermore, the ALFF and ReHo values in the anterior cuneiform and frontal lobes of the TBI group were lower than those in the CVD group. In contrast, the ALFF and ReHo values were elevated in the precuneus and frontal brain regions of the CVD group compared to the TBI group, which could explain the improved levels of consciousness.\u003c/p\u003e\n\u003cp\u003eThis study is subject to certain limitations. Primarily, the inclusion of only two DoC injury types and a relatively small sample size necessitates the conduct of large multicenter studies encompassing multiple injury types to enable a comprehensive evaluation of the impact of network connectivity on patient prognosis. In this study, DoC patients with cardiovascular disease were utilized as a control group. However, the inclusion of additional suitable control groups, such as normal participants, is essential to effectively observe differences in injury types and to determine treatment effects. Furthermore, this study is a retrospective study with information bias. To mitigate this, we have blinded the data collection and used objective criteria to obtain the information, thereby minimizing bias. Nevertheless, this study is the first to evaluate the performance of ALFF and ReHo in resting patients with cardiovascular disease using fMRI techniques.\u003c/p\u003e\n\u003cp\u003eThis study identified ALFF and ReHo enhancement in the precuneus and frontal lobes of patients with DoC, which might be the anatomical basis for possible improvements in consciousness. Routine preoperative rs-fMRI should be considered to improve awakening therapy recovery rates.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank Professor Zongsheng Xu for providing rs-fMRI data of DoC patients.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe obtained the clinical data from XQ, XC, and HN. HN performed the follow-up analysis of the post-operative state and performed a neurological evaluation on SW. XQ and XC drafted the manuscript. The manuscript was critically revised by LY, JH, and XG for important intellectual content. XQ, XC, and SW performed the statistical analysis. LY, XG, and XL supervised the study. All authors approved the final draft.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was funded by STI2030-Major Projects +2021ZD0204300\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBy the Declaration of Helsinki, this study was approved by the Institutional Review Board (or Ethics Committee) of Peking University International Hospital (2022-KY-0023-01, 01/04/2022). for studies involving humans. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eResearchers declare that there were no commercial or financial relationships that could potentially conflict with their research\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDatasets used and/or analyzed during the current study are available from the corresponding author.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGiacino JT, Fins JJ, Laureys S, Schiff ND. 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J Trauma Acute Care Surg. 2018;85(1):155\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/TA.0000000000001852\u003c/span\u003e\u003cspan address=\"10.1097/TA.0000000000001852\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\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":"resting-state functional MRI, amplitude of low-frequency fluctuations, regional homogeneity, Disorder of consciousness, Injury type, Anterior cuneate lobe, Frontal lobe","lastPublishedDoi":"10.21203/rs.3.rs-4614073/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4614073/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eDisorder of consciousness (DoC) is an impaired state of consciousness. This study used the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) measures obtained from resting-state functional magnetic resonance imaging (rs-fMRI) to observe neuronal activity changes in patients with DoC from various injuries for prognostic predictions.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis study included six patients with traumatic brain injury (TBI)-induced DoC and six patients with cerebrovascular disease (CVD)-induced DoC. Images were processed using Data Processing Assistant for rs-fMRI software to obtain the ALFF and ReHo values.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe ALFF values were lower in the TBI group than in the CVD (i.e., control) group for the Precuneus_R, Superior frontal gyrus_R, Middle frontal gyrus, Middle occipital gyrus, and Hippocampus_R but higher for the bilateral insula, Postcentral gyrus_L, right moment gyrus, Superior parietal gyrus_L, and Inferior temporal gyrus_L. The ReHo values were higher in the TBI group than in the CVD group for the Precental gyrus_L and Postcentral gyrus_L, Middle temporal gyrus_R, right superior temporal gyrus, Superior temporal gyrus_R, Superior parietal gyrus_L, Superior frontal gyrus_R, and Inferior frontal gyrus)_L but lower for the Insula_R, Postcentral gyrus_R, Inferior frontal gyrus, Orbital part_L, straight gyrus, and Anterior cingulate_L. Consciousness improved in three patients with CVD DoC and one with TBI DoC.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eALFF and ReHo enhancements in the precuneus and frontal lobes on rs-fMRI might suggest improved consciousness for patients with CVD and TBI DoC.\u003c/p\u003e","manuscriptTitle":"Assessing brain activity in patients with disorder of consciousness using the amplitude of low-frequency fluctuations and regional homogeneity derived from resting-state functional magnetic resonance images","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-18 18:25:46","doi":"10.21203/rs.3.rs-4614073/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":"63821c8e-c91e-43cb-817a-cc1b1b2029e6","owner":[],"postedDate":"July 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-11-13T08:54:08+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-18 18:25:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4614073","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4614073","identity":"rs-4614073","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}