Dynamic gray matter and intrinsic activity changes after epilepsy surgery.

OBJECTIVES: To explore the dynamic changes of gray matter volume and intrinsic brain activity following anterior temporal lobectomy (ATL) in patients with unilateral mesial temporal lobe epilepsy (mTLE) who achieved seizure-free for 2 years. MATERIALS AND METHODS: High-resolution T1-weighted MRI and resting-state functional MRI data were obtained in ten mTLE patients at five serial timepoints: before surgery, 3, 6, 12, and 24 months after surgery. The gray matter volume (GMV) and amplitude of low-frequency fluctuations (ALFF) were compared among the five scans to depict the dynamic changes after ATL. RESULTS: After successful ATL, GMV decreased in several ipsilateral brain regions: ipsilateral insula, thalamus, and putamen showed gradual gray matter atrophy from 3 to 24 months, while ipsilateral superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus, middle occipital gyrus, inferior occipital gyrus, caudate nucleus, lingual gyrus, and fusiform gyrus showed significant GMV decrease at 3 months follow-up, without further changes. Ipsilateral insula showed gradual ALFF decrease from 3 to 24 months after surgery. Ipsilateral superior temporal gyrus showed ALFF decrease at 3 months follow-up, without further changes. Ipsilateral thalamus and cerebellar vermis showed obvious ALFF increase after surgery. CONCLUSIONS: Surgical resection may lead to a short-term reduction of gray matter volume and intrinsic brain activity in neighboring regions, while the progressive gray matter atrophy may be due to possible intrinsic mechanism of mTLE. Dynamic ALFF changes provide evidence that disrupted focal spontaneous activities were reorganized after successful surgery.

Real-time effects of interictal spikes on hippocampus and amygdala functional connectivity in unilateral temporal lobe epilepsy: An EEG-fMRI study.

OBJECTIVE: To explore the real-time effects of interictal epileptiform discharges (IEDs) on hippocampus and amygdala functional connectivity (FC) in unilateral temporal lobe epilepsy (TLE). METHODS: Patients with unilateral TLE were recruited and underwent simultaneous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) scanning. Simultaneous EEG was used to define the prespike (10 s before spike) and postspike (10 s after spike) periods. Dynamic FC analysis was applied using the left/right hippocampus and amygdala separately as a seed region to map the network alterations after IED occurrence. RESULTS: A total of 261 IED events (133 left, 128 right) from 21 patients with unilateral TLE (10 left, 11 right) were analyzed. Left IEDs had a greater influence on the hippocampus-seeded networks, whereas right IEDs affected the amygdala-seeded networks more. Left IEDs disconnected the ipsilateral hippocampus and the default mode network, which might be related to cognitive impairment in TLE. The reward-emotion network (more of the prefrontal-limbic system) and visual network also showed FC changes after left IEDs. The reward-emotion network (more of the reward system) was coactivated after right IEDs, indicating a possible mechanism of forced normalization. SIGNIFICANCE: This study directly linked the disrupted functional networks in TLE to epileptic activities and offered a unique tool for future research to investigate mechanisms of comorbidities in TLE.

Differences of individual gray matter networks between MCI patients who converted to AD within 3 Years and nonconverters.

Objective: Here we aimed to explore the differences in individual gray matter (GM) networks at baseline in mild cognitive impairment patients who converted to Alzheimer's disease (AD) within 3 years (MCI-C) and nonconverters (MCI-NC). Materials and methods: Data from 461 MCI patients (180 MCI-C and 281 MCI-NC) were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI). For each subject, a GM network was constructed using 3D-T1 imaging and the Kullback-Leibler divergence method. Gradient and topological analyses of individual GM networks were performed, and partial correlations were calculated to evaluate relationships among network properties, cognitive function, and apolipoprotein E (APOE) €4 alleles. Subsequently, a support vector machine (SVM) model was constructed to discriminate the MCI-C and MCI-NC patients at baseline. Results: The gradient analysis revealed that the principal gradient score distribution was more compressed in the MCI-C group than in the MCI-NC group, with scores for the left lingual gyrus, right fusiform gyrus and left middle temporal gyrus being increased in the MCI-C group (p < 0.05, FDR corrected). The topological analysis showed significant differences in nodal efficiency in four nodes between the two groups. Furthermore, the regional gradient scores or nodal efficiency were found to be significantly related to the neuropsychological test scores, and the left middle temporal gyrus gradient scores were positively associated with the number of APOE €4 alleles (r = 0.192, p = 0.002). Ultimately, the SVM model achieved a balanced accuracy of 79.4% in classifying MCI-C and MCI-NC patients (p < 0.001). Conclusion: The whole-brain GM network hierarchy in the MCI-C group was more compressed than that in the MCI-NC group, suggesting more serious cognitive impairments in the MCI-C group. The left middle temporal gyrus gradient scores were related to both cognitive function and APOE €4 alleles, thus serving as potential biomarkers distinguishing MCI-C from MCI-NC at baseline.

Dynamics of the Brain Functional Network Associated With Subjective Cognitive Decline and Its Relationship to Apolipoprotein E €4 Alleles.

The aim of our study was to explore the dynamic functional alterations in the brain in patients with subjective cognitive decline (SCD) and their relationship to apolipoprotein E (APOE) €4 alleles. In total, 95 SCD patients and 49 healthy controls (HC) underwent resting-state functional magnetic resonance imaging (rs-fMRI). Then, the mean time series of 90 cortical or subcortical regions were extracted based on anatomical automatic labeling (AAL) atlas from the preprocessed rs-fMRI data. The static functional connectome (SFC) and dynamic functional connectome (DFC) were constructed and compared using graph theory methods and leading eigenvector dynamics analysis (LEiDA), respectively. The SCD group displayed a shorter lifetime (p = 0.003, false discovery rate corrected) and lower probability (p = 0.009, false discovery rate corrected) than the HC group in a characteristic dynamic functional network mainly involving the bilateral insular and temporal neocortex. No significant differences in the SFC were detected between the two groups. Moreover, the lower probability in the SCD group was found to be negatively correlated with the number of APOE ε4 alleles (r = -0.225, p = 0.041) in a partial correlation analysis with years of education as a covariate. Our results suggest that the DFC may be a more sensitive parameter than the SFC and can be used as a potential biomarker for the early detection of SCD.

Topological Alterations of the Brain Functional Network in Type 2 Diabetes Mellitus Patients With and Without Mild Cognitive Impairment.

The aim of this study was to explore the topological alterations of the brain functional network in type 2 diabetes mellitus (T2DM) patients with and without mild cognitive impairment (MCI) using resting-state functional magnetic resonance imaging (rs-fMRI) and graph theory approaches. In total, 27 T2DM patients with MCI, 27 T2DM patients without MCI, and 27 healthy controls (HCs) underwent rs-fMRI scanning. The whole-brain functional network was constructed by thresholding the Pearson's correlation matrices of 90 brain regions. The topological organization of the constructed networks was analyzed by using graph theory approaches. The global and nodal properties of the participants in the three groups were compared by using one-way ANOVA as well as post hoc Tukey's t-tests. The relationships between the altered topological properties and clinical features or scores of neuropsychological tests were analyzed in T2DM patients with MCI. At the global level, the global and local efficiency of the patients in the T2DM with MCI group were significantly higher than that of participants in the HCs group, and the length of the characteristic path was significantly lower than that of the participants in the HCs group (p < 0.05). No significant difference was found among the other groups. At the nodal level, when compared with T2DM patients without MCI, T2DM patients with MCI showed significantly increased nodal centrality in four brain regions, which were mainly located in the orbitofrontal lobe and anterior cingulate gyrus (ACG) (p < 0.05). No significant difference was found between the T2DM patients without MCI and HCs. Moreover, nodal degree related coefficient (r = -0381, p = 0.050) and nodal efficiency (r = -0.405, P = 0.036) of the ACG showed a significant closed correlation with the scores of the digit span backward test in the T2DM patients with MCI. Our results suggested that the increased nodal properties in brain regions of the orbitofrontal lobe and ACG were biomarkers of cognitive impairment in T2DM patients and could be used for its early diagnosis. The global topological alterations may be related to the combination of MCI and T2DM, rather than any of them.

Structural and functional reorganization of contralateral hippocampus after temporal lobe epilepsy surgery.

OBJECTIVE: To explore the structural and functional reorganization of contralateral hippocampus in patients with unilateral mesial temporal lobe epilepsy (mTLE) who achieved seizure-freedom after anterior temporal lobectomy (ATL). METHODS: We obtained high-resolution structural MRI and resting-state functional MRI data in 28 unilateral mTLE patients and 29 healthy controls. Patients were scanned before and three and 24 months after surgery while controls were scanned only once. Hippocampal gray matter volume (GMV) and functional connectivity (FC) were assessed. RESULTS: No obvious GMV changes were observed in contralateral hippocampus before and after successful surgery. Before surgery, ipsilateral hippocampus showed increased FC with ipsilateral insula (INS) and temporoparietal junction (TPJ), but decreased FC with widespread bilateral regions, as well as contralateral hippocampus. After successful ATL, contralateral hippocampus showed: (1) decreased FC with ipsilateral INS at three months follow-up, without further changes; (2) decreased FC with ipsilateral TPJ, postcentral gyrus and rolandic operculum at three months, with an obvious increase at 24 months follow-up; (3) increased FC with bilateral medial prefrontal cortex (MPFC) and superior frontal gyrus (SFG) at three months follow-up, without further changes. CONCLUSIONS: Successful ATL may not lead to an obvious structural reorganization in contralateral hippocampus. Surgical manipulation may lead to a transient FC reduction of contralateral hippocampus. Increased FC between contralateral hippocampus and bilateral MPFC and SFG may be related to postoperative functional remodeling.

Machine learning for detecting mesial temporal lobe epilepsy by structural and functional neuroimaging.

Mesial temporal lobe epilepsy (mTLE), the most common type of focal epilepsy, is associated with functional and structural brain alterations. Machine learning (ML) techniques have been successfully used in discriminating mTLE from healthy controls. However, either functional or structural neuroimaging data are mostly used separately as input, and the opportunity to combine both has not been exploited yet. We conducted a multimodal ML study based on functional and structural neuroimaging measures. We enrolled 37 patients with left mTLE, 37 patients with right mTLE, and 74 healthy controls and trained a support vector ML model to distinguish them by using each measure and the combinations of the measures. For each single measure, we obtained a mean accuracy of 74% and 69% for discriminating left mTLE and right mTLE from controls, respectively, and 64% when all patients were combined. We achieved an accuracy of 78% by integrating functional data and 79% by integrating structural data for left mTLE, and the highest accuracy of 84% was obtained when all functional and structural measures were combined. These findings suggest that combining multimodal measures within a single model is a promising direction for improving the classification of individual patients with mTLE.

A transdiagnostic neuroanatomical signature of psychiatric illness.

Despite an increasing focus on transdiagnostic approaches to mental health, it remains unclear whether different diagnostic categories share a common neuronatomical basis. The current investigation sought to investigate whether a transdiagnostic set of structural alterations characterized schizophrenia, depression, post-traumatic stress disorder, and obsessive-compulsive disorder, and determine whether any such alterations reflected markers of psychiatric illness or pre-existing familial vulnerability. A total of 404 patients with a psychiatric diagnosis were recruited (psychosis, n = 129; unipolar depression, n = 92; post-traumatic stress disorder, n = 91; obsessive-compulsive disorder, n = 92) alongside n = 201 healthy controls and n = 20 unaffected first-degree relatives. We collected structural magnetic resonance imaging scans from each participant, and tested for transdiagnostic alterations using Voxel-based morphometry. Inferences were made at p < 0.05 after family-wise error correction for multiple comparisons. The four psychiatric groups relative to healthy controls were all characterized by significantly greater gray matter volume in the putamen (right: z-score: 5.97, p-value < 0.001; left: z-score: 4.97, p-value = 0.001); the volume of this region was positively correlated with severity of symptoms across groups (r = 0.313; p < 0.001). Putamen enlargement was also evident in unaffected relatives compared to healthy controls (right: z-score: 8.13, p-value < 0.001; left: z-score: 9.38, p-value < 0.001). Taken collectively, these findings indicate that increased putamen volume may reflect a transdiagnostic marker of familial vulnerability to psychopathology. This is consistent with emerging conceptualizations of psychiatric illness, in which each disorder is understood as a combination of diagnosis-specific features and a transdiagnostic factor reflecting general psychopathology.

Dysconnectivity of the medio-dorsal thalamic nucleus in drug-naïve first episode schizophrenia: diagnosis-specific or trans-diagnostic effect?

Converging lines of evidence implicate the thalamocortical network in schizophrenia. In particular, the onset of the illness is associated with aberrant functional integration between the medio-dorsal thalamic nucleus (MDN) and widespread prefrontal, temporal and parietal cortical regions. Because the thalamus is also implicated in other psychiatric illnesses including post-traumatic stress disorder (PTSD) and major depressive disorder (MDD), the diagnostic specificity of these alterations is unclear. Here, we determined whether aberrant functional integration between the MDN and the cortex is a specific feature of schizophrenia or a trans-diagnostic feature of psychiatric illness. Effective connectivity (EC) between the MDN and rest of the cortex was measured by applying psychophysiological interaction analysis to resting-state functional magnetic resonance imaging data of 50 patients with first episode schizophrenia (FES), 50 patients with MDD, 50 patients with PTSD and 122 healthy controls. All participants were medication-naïve. The only significant schizophrenia-specific effect was increased EC between the right MDN and the right pallidum (p < 0.05 corrected). In contrast, there were a number of significant trans-diagnostic alterations, with both right and left MDN displaying trans-diagnostic increased EC with several prefrontal and parietal regions bilaterally (p < 0.05 corrected). EC alterations between the MDN and the cortex are not specific to schizophrenia but are a trans-diagnostic feature of psychiatric disorders, consistent with emerging conceptualizations of mental illness based on a single general psychopathology factor. Therefore, dysconnectivity of the MDN could potentially be used to assess the presence of general psychopathology above and beyond traditional diagnostic boundaries.

Different patterns of white matter changes after successful surgery of mesial temporal lobe epilepsy.

OBJECTIVES: To explore the dynamic changes of white matters following anterior temporal lobectomy (ATL) in mesial temporal lobe epilepsy (MTLE) patients who achieved seizure-free at two-year follow-up. METHODS: Diffusion tensor imaging (DTI) was obtained in ten MTLE patients at five serial time points: before surgery, three months, six months, 12 months and 24 months after surgery, as well as in 11 age- and sex-matched healthy controls at one time point. Regions with significant postoperative fractional anisotropy (FA) changes and their dynamic changes were confirmed by comparing all preoperative and postoperative data using Tract-Based Spatial Statistics (TBSS). RESULTS: After successful ATL, significant FA changes were found in widespread ipsilateral and contralateral white matter regions (P <.05, FWE correction). Ipsilateral external capsule, cingulum, superior corona radiate, body of corpus callosum, inferior longitudinal fasciculus, optic radiation and contralateral inferior cerebellar peduncle, inferior longitudinal fasciculus showed significant FA decrease at three months after surgery, without further changes. Ipsilateral superior cerebellar peduncle and contralateral corpus callosum, anterior corona radiate, external capsule, optic radiation showed significant FA decrease at three months follow up but increase later. Ipsilateral cerebral peduncle and contralateral middle cerebellar peduncle showed significant FA decrease at three months follow up, with further decrease after that. While ipsilateral posterior limb of internal capsule, retrolenticular part of internal capsule and contralateral posterior corona radiate showed significant FA increase after surgery. CONCLUSIONS: FA changes after successful ATL presented as four distinct patterns, reflecting different structural adaptions following epilepsy surgery. Some FA increases indicated the reversibility of preoperative diffusion abnormalities and the possibility of structural reorganization, especially in the contralateral hemisphere.

White matter volume loss in amyotrophic lateral sclerosis: A meta-analysis of voxel-based morphometry studies.

Structural neuroimaging studies of white matter (WM) volume in amyotrophic lateral sclerosis (ALS) using voxel-based morphometry (VBM) have yielded inconsistent findings. This study aimed to perform a quantitative voxel-based meta-analysis using effect-size signed differential mapping (ES-SDM) to establish a statistical consensus between published studies for WM volume alterations in ALS. The pooled meta-analysis revealed significant WM volume losses in the bilateral supplementary motor areas (SMAs), bilateral precentral gyri (PGs), left middle cerebellar peduncle and right cerebellum in patients with ALS, involving the corticospinal tract (CST), interhemispheric fibers, subcortical arcuate fibers, projection fibers to the striatum and cortico-ponto-cerebellar tract. The meta-regression showed that the ALS functional rating scale-revised (ALSFRS-R) was positively correlated with decreased WM volume in the bilateral SMAs, whereas illness duration was negatively correlated with WM volume reduction in the right SMA. This study provides a thorough profile of WM volume loss in ALS and robust evidence that ALS is a multisystem neurodegenerative disease that involves a variety of subcortical WM tracts extending beyond motor cortex involvement.