Voxel-based morphometry and intellectual assessment in patients with congenital bilateral perisylvian syndrome

Congenital bilateral perisylvian syndrome (CBPS) presents with heterogeneous clinical manifestations such as pseudobulbar palsy, language disorder, variable cognitive deficits, epilepsy, and perisylvian abnormalities (most frequently polymicrogyria) on imaging studies. We investigated the relationship between seizures and extent of gray matter (GM) and white matter (WM) abnormalities using voxel-based morphometry (VBM) of brain magnetic resonance imaging (MRI) as well the association between seizures, structural abnormalities and cognitive ability. In this cross-sectional study, we evaluated 51 healthy volunteers and 18 patients with CBPS with epilepsy (seizure group, n = 7) and without (non-seizure group, n = 11). We used VBM (SPM8/DARTEL) to investigate areas with excess and atrophy of both gray and white matter, comparing groups of patients with controls. Intellectual ability of patients was assessed by the WISC-III or WAIS-III. Both groups with CBPS and the control group were homogeneous with respect to gender (p = 0.07) and age (p = 0.065). Besides perisylvian polymicrogyria, the seizure group exhibited areas with GM and WM reduction including temporal, frontal, parietal and occipital lobes. In contrast, we identified fewer areas with GM and WM reduction in the non-seizure group. The seizure group presented worse intellectual performance (performance IQ and global IQ) than the non-seizure group. The seizure group presented with a more widespread pattern of cortical and sub-cortical abnormalities, as well as worse cognition. Our results suggest that patients with CBPS and epilepsy appear to have widespread neuronal damage that goes beyond the areas with MRI-visible perisylvian polymicrogyria.     

White matter abnormalities in subjects at ultra high-risk for schizophrenia and first-episode schizophrenic patients

Schizophrenia is associated with neuroanatomical abnormalities. Gray matter decrease seems to predate first schizophrenic episode. Whether white matter abnormalities predate the onset of psychotic symptoms is unclear. We investigated this issue using voxel-based morphometry (VBM) of structural magnetic resonance images to examine individuals with prodromal symptoms who were at ultra high-risk (UHR) of developing schizophrenia and compared them to first-episode schizophrenic patients and healthy controls. White matter volume maps from high-resolution magnetic resonance T1 weighted whole brain images were analyzed in a cross-sectional study using SPM2 in 30 UHR patients, 23 first-episode schizophrenic patients and 29 healthy controls. UHR patients showed significant lower white matter volume in the right superior temporal lobe compared to healthy controls. First-episode patients with schizophrenia showed widespread smaller white matter volume bilaterally compared to UHR patients. This study provides first evidence for smaller white matter volume in the right temporal lobe of UHR patients, one of the key structures in the pathophysiology of schizophrenia. Furthermore, white matter abnormalities seem to progress after transition into schizophrenia.     

No change to grey and white matter volumes in bipolar I disorder patients

BACKGROUND: Structural brain imaging is assumed to be a key method to elucidate the underlying neuropathology of bipolar disorder. However, magnetic resonance imaging studies using region of interest analysis and voxel-based morphometry (VBM) revealed quite inconsistent findings. Hence, there is no clear evidence so far for core regions of cortical or subcortical structural abnormalities in bipolar disorder. The aim of this study was to investigate grey and white matter volumes in a large sample of patients with bipolar I disorder. METHODS: Thirty-five patients with bipolar I disorder and 32 healthy controls matched with respect to gender, handedness and education participated in the study. MRI scanning was performed and an optimized VBM analysis was conducted. RESULTS: We could not observe any significant differences of grey or white matter volumes between patients with bipolar disorder and healthy control subjects. Additional analyses did not reveal significant correlations between grey or white matter volume with number of manic or depressive episodes, duration of illness, existence of psychotic symptoms, and treatment with lithium or antipsychotics. CONCLUSIONS: With this VBM study we were not able to identify core regions of structural abnormalities in bipolar disorder.     

强迫症患者脑结构异常的多模态研究

目的探讨强迫症患者脑灰质和白质结构改变是否在同一样本中反映了相同环路的异常。方法对54例强迫症患者(强迫症组)和54名健康对照(对照组)进行3D结构磁共振成像扫描和弥散张量成像扫描。基于SPM分析软件,采用基于体素的形态学分析方法分析强迫症组全脑灰质体积与对照组的差异;基于FSL软件,采用基于纤维束示踪的空间统计学探讨强迫症组各向异性分数(fractional anisotropy,FA)与对照组的差异。结果与对照组相比,强迫症组左侧额中回、左侧前扣带和旁扣带脑回、左侧中央前回及右侧颞下回灰质体积减小(P<0.05,Alphasim校正),胼胝体体部和胼胝体膝部FA值减小(P<0.05,FWE校正)。结论强迫症患者的灰质体积和白质完整性均存在异常,且异常区域多位于皮质-纹状体-丘脑-皮质环路相关脑区,强迫症的灰、白质结构异常可能同时出现。     

White matter alterations following thromboembolic stroke: a β-amyloid precursor protein immunocytochemical study in rats

Thromboembolic stroke in rats leads to a well-described pattern of histopathological and behavioral abnormalities. However, limited data are available in animal models concerning the response of the white matter to embolic events. The purpose of this study was to document patterns of white matter abnormalities using β-amyloid precursor protein (βAPP) immunocytochemistry as a marker of axonal damage. Twelve male Wistar rats underwent photochemically induced right common carotid artery thrombosis (CCAT) or sham procedures. At 3 days after CCAT, rats were perfusion-fixed and sections immunostained for the visualization of βAPP or stained with hematoxylin and eosin for routine histopathological analysis. As previously described, CCAT produced small ipsilateral embolic infarcts and ischemic cell change within gray matter structures including the medial cerebral cortex, striatum, hippocampus and thalamus. In areas of frank infarction, numerous reactive profiles were observed within borderzones of the damaged site. However, βAPP immunocytochemistry also revealed reactive axonal profiles within various white matter tracts including the corpus callosum, external capsule and fimbria of the hippocampus. In many cases, the presence of axonal damage could not be appreciated with routine hematoxylin and eosin staining. These data indicate that CCAT leading to platelet embolization to the brain not only produces embolic infarcts but also produces more subtle white matter abnormalities. Previously undetected white matter damage would be expected to participate in the sensorimotor and cognitive behavioral deficits following embolic stroke. Received: 8 August 1997 / Revised, accepted: 10 November 1997     

Multivariate pattern analysis reveals subtle brain anomalies relevant to the cognitive phenotype in neurofibromatosis type 1

Neurofibromatosis Type 1 (NF1) is a common genetic condition associated with cognitive dysfunction. However, the pathophysiology of the NF1 cognitive deficits is not well understood. Abnormal brain structure, including increased total brain volume, white matter (WM) and grey matter (GM) abnormalities have been reported in the NF1 brain. These previous studies employed univariate model‐driven methods preventing detection of subtle and spatially distributed differences in brain anatomy. Multivariate pattern analysis allows the combination of information from multiple spatial locations yielding a discriminative power beyond that of single voxels. Here we investigated for the first time subtle anomalies in the NF1 brain, using a multivariate data‐driven classification approach. We used support vector machines (SVM) to classify whole‐brain GM and WM segments of structural T₁‐weighted MRI scans from 39 participants with NF1 and 60 non‐affected individuals, divided in children/adolescents and adults groups. We also employed voxel‐based morphometry (VBM) as a univariate gold standard to study brain structural differences. SVM classifiers correctly classified 94% of cases (sensitivity 92%; specificity 96%) revealing the existence of brain structural anomalies that discriminate NF1 individuals from controls. Accordingly, VBM analysis revealed structural differences in agreement with the SVM weight maps representing the most relevant brain regions for group discrimination. These included the hippocampus, basal ganglia, thalamus, and visual cortex. This multivariate data‐driven analysis thus identified subtle anomalies in brain structure in the absence of visible pathology. Our results provide further insight into the neuroanatomical correlates of known features of the cognitive phenotype of NF1. Hum Brain Mapp 35:89–106, 2014. © 2012 Wiley Periodicals, Inc.     

Thalamic atrophy in childhood absence epilepsy

PURPOSE: Patients with childhood absence epilepsy (CAE) have normal clinical magnetic resonance imaging (MRI) studies. The presence of abnormalities in corticothalamic networks has been suggested to be the functional basis of absence seizure generation. We assessed whether structural grey and white matter volume changes of these areas occurred in patients with absence seizures by using optimized voxel-based morphometry (VBM). METHODS: We recruited 13 patients with a clinical and EEG diagnosis of CAE (mean age at examination, 17 +/- 8 years) and compared them with a consecutive series of 109 controls (mean age, 29 +/- 9 years). The 3 tesla MRI examination included a 3D T(1)-weighted sequence, which was analyzed with an optimized VBM protocol using the SPM2 package. The threshold was set at p < 0.05, corrected for multiple comparisons. RESULTS: Compared with controls, CAE patients showed areas of grey matter decrease in both thalami and in the subcallosal gyrus. White matter decrease was found in the extranuclear subcortical area and in the white matter of the basal forebrain. Grey and white matter increase was restricted to small clusters of cortical and subcortical areas. CONCLUSIONS: Evidence exists of subcortical grey and white matter volume reduction in CAE patients. Bilateral thalamic atrophy may be either a result of damage from seizures (as in hippocampal sclerosis) or a reflection of a primary underlying pathology as the cause of absence seizures.     

Voxel-based morphometric analyses of the brain in children and adolescents prenatally exposed to alcohol

Children of mothers who abuse alcohol during pregnancy can suffer varying degrees of neurological abnormality, cognitive impairment, and behavioral problems, and in the worst case, are diagnosed with fetal alcohol syndrome (FAS). The purpose of the present study was to localize brain abnormalities in a group of children and adolescents prenatally exposed to alcohol using high resolution, 3D structural MRI data and whole-brain voxel-based morphometry (VBM). Data were collected for 21 children and adolescents with histories of prenatal alcohol exposure (ALC) and 21 normally developing individuals. Statistical parametric maps revealed abnormalities most prominent in the left hemisphere perisylvian cortices of the temporal and parietal lobes where the ALC patients tended to have too much gray matter and not enough white matter. These results provide further support for dysmorphology in temporo-parietal cortices above and beyond the overall microcephaly that results from severe prenatal alcohol exposure.     

Reduced gray matter volume of dorsal cingulate cortex in patients with obsessive-compulsive disorder: a voxel-based morphometric study

Aims: Previous morphometric studies using magnetic resonance imaging (MRI) have revealed structural brain abnormalities in obsessive–compulsive disorder (OCD). The aim of the present study was to investigate the alterations in brain structure of patients with OCD using a voxel‐based morphometry (VBM) method. Methods: Sixteen patients with OCD free of comorbid major depression, and 32 sex‐ and age‐matched healthy subjects underwent MRI using a 1.5‐T MR scanner. OCD severity was assessed with the Yale–Brown Obsessive–Compulsive Scale (mean ± SD: 22 ± 7.6; range: 7–32). MR images were spatially normalized and segmented using the VBM5 package ( http://dbm.neuro.uni‐jena.de/vbm/ ). Statistical analysis was performed using statistical parametric mapping software. Results: Significant reductions in regional gray matter volume were detected in the left caudal anterior cingulate cortex and right dorsal posterior cingulate cortex in the patients with OCD as compared to healthy controls (uncorrected, P < 0.001). No significant differences in white matter volumes were observed in any brain regions of the patients. No significant correlation between Yale–Brown Obsessive–Compulsive Scale score and regional gray matter or white matter volume was observed. Conclusions: Regional gray matter alteration in the dorsal cingulate cortex, which is suggested to play a role in non‐emotional cognitive processes, may be related to the pathophysiology in OCD.     

Regional gray matter abnormalities in panic disorder: A voxel-based morphometry study

Although abnormalities in brain structures involved in the neurobiology of fear and anxiety have been implicated in the pathophysiology of panic disorder (PD), relatively few studies have made use of voxel-based morphometry (VBM) magnetic resonance imaging (MRI) to determine structural brain abnormalities in PD. We have assessed gray matter volume in 19 PD patients and 20 healthy volunteers using VBM. Images were acquired using a 1.5 T MRI scanner, and were spatially normalized and segmented using optimized VBM. Statistical comparisons were performed using the general linear model. A relative increase in gray matter volume was found in the left insula of PD patients compared with controls. Additional structures showing differential increases were the left superior temporal gyrus, the midbrain, and the pons. A relative gray matter deficit was found in the right anterior cingulate cortex. The insula and anterior cingulate abnormalities may be relevant to the pathophysiology of PD, since these structures participate in the evaluation process that ascribes negative emotional meaning to potentially distressing cognitive and interoceptive sensory information. The abnormal brain stem structures may be involved in the generation of panic attacks.     

Regional gray matter abnormalities in panic disorder: a voxel-based morphometry study

Although abnormalities in brain structures involved in the neurobiology of fear and anxiety have been implicated in the pathophysiology of panic disorder (PD), relatively few studies have made use of voxel-based morphometry (VBM) magnetic resonance imaging (MRI) to determine structural brain abnormalities in PD. We have assessed gray matter volume in 19 PD patients and 20 healthy volunteers using VBM. Images were acquired using a 1.5 T MRI scanner, and were spatially normalized and segmented using optimized VBM. Statistical comparisons were performed using the general linear model. A relative increase in gray matter volume was found in the left insula of PD patients compared with controls. Additional structures showing differential increases were the left superior temporal gyrus, the midbrain, and the pons. A relative gray matter deficit was found in the right anterior cingulate cortex. The insula and anterior cingulate abnormalities may be relevant to the pathophysiology of PD, since these structures participate in the evaluation process that ascribes negative emotional meaning to potentially distressing cognitive and interoceptive sensory information. The abnormal brain stem structures may be involved in the generation of panic attacks.     

Altered white matter integrity in temporal lobe epilepsy: Association with cognitive and clinical profiles

Purpose: Diffusion tensor imaging (DTI) studies have reported substantial white matter abnormalities in patients with temporal lobe epilepsy (TLE). However, limited data exist regarding the extent of white matter tract abnormalities, cognitive effects of these abnormalities, and relationship to clinical factors. The current study examined these issues in subjects with chronic TLE. Methods: DTI data were obtained in 12 TLE subjects and 10 age‐matched healthy controls. Voxel‐wise statistical analysis of fractional anisotropy (FA) was carried out using tract‐based spatial statistics (TBSS). White matter integrity was correlated with cognitive performance and epilepsy‐related clinical parameters. Results: Subjects with TLE, as compared to healthy controls, demonstrated four clusters of reduced FA, in anterior temporal lobe, mesial temporal lobe, and cerebellum ipsilateral, as well as frontoparietal lobe contralateral to the side of seizure onset. Mean FA was positively correlated with delayed memory, in anterior temporal lobe; and immediate memory, in mesial temporal lobe. Lower FA values in the posterior region of corpus callosum were related to earlier age of seizure onset. Conclusion: TLE is associated with widespread disturbances in white matter tracts and these changes have important cognitive and clinical consequences.     

White matter volume alterations in hair-pulling disorder (trichotillomania)

Trichotillomania (TTM) is a disorder characterized by repetitive hair-pulling resulting in hair loss. Key processes affected in TTM comprise affective, cognitive, and motor functions. Emerging evidence suggests that brain matter aberrations in fronto-striatal and fronto-limbic brain networks and the cerebellum may characterize the pathophysiology of TTM. The aim of the present voxel-based morphometry (VBM) study was to evaluate whole brain grey and white matter volume alteration in TTM and its correlation with hair-pulling severity. High-resolution magnetic resonance imaging (3 T) data were acquired from 29 TTM patients and 28 age-matched healthy controls (CTRLs). All TTM participants completed the Massachusetts General Hospital Hair-Pulling Scale (MGH-HPS) to assess illness/pulling severity. Using whole-brain VBM, between-group differences in regional brain volumes were measured. Additionally, within the TTM group, the relationship between MGH-HPS scores, illness duration and brain volumes were examined. All data were corrected for multiple comparisons using family-wise error (FWE) correction at p?<?0.05. Patients with TTM showed larger white matter volumes in the parahippocampal gyrus and cerebellum compared to CTRLs. Estimated white matter volumes showed no significant association with illness duration or MGH-HPS total scores. No significant between-group differences were found for grey matter volumes. Our observations suggest regional alterations in cortico-limbic and cerebellar white matter in patients with TTM, which may underlie deficits in cognitive and affective processing. Such volumetric white matter changes may precipitate impaired cortico-cerebellar communication leading to a reduced ability to control hair pulling behavior.

     

Broad white matter impairment in multiple system atrophy

Multiple system atrophy (MSA) is a rare neurodegenerative disorder characterized by the widespread aberrant accumulation of α‐synuclein (α‐syn). MSA differs from other synucleinopathies such as Parkinson''s disease (PD) in that α‐syn accumulates primarily in oligodendrocytes, the only source of white matter myelination in the brain. Previous MSA imaging studies have uncovered focal differences in white matter. Here, we sought to build on this work by taking a global perspective on whole brain white matter. In order to do this, in vivo structural imaging and diffusion magnetic resonance imaging were acquired on 26 MSA patients, 26 healthy controls, and 23 PD patients. A refined whole brain approach encompassing the major fiber tracts and the superficial white matter located at the boundary of the cortical mantle was applied. The primary observation was that MSA but not PD patients had whole brain deep and superficial white matter diffusivity abnormalities (p < .001). In addition, in MSA patients, these abnormalities were associated with motor (Unified MSA Rating Scale, Part II) and cognitive functions (Mini‐Mental State Examination). The pervasive whole brain abnormalities we observe suggest that there is widespread white matter damage in MSA patients which mirrors the widespread aggregation of α‐syn in oligodendrocytes. Importantly, whole brain white matter abnormalities were associated with clinical symptoms, suggesting that white matter impairment may be more central to MSA than previously thought.     

MP2RAGE multispectral voxel‐based morphometry in focal epilepsy

We assessed the applicability of MP2RAGE for voxel‐based morphometry. To this end, we analyzed its brain tissue segmentation characteristics in healthy subjects and the potential for detecting focal epileptogenic lesions (previously visible and nonvisible). Automated results and expert visual interpretations were compared with conventional VBM variants (i.e., T1 and T1 + FLAIR). Thirty‐one healthy controls and 21 patients with focal epilepsy were recruited. 3D T1‐, T2‐FLAIR, and MP2RAGE images (consisting of INV1, INV2, and MP2 maps) were acquired on a 3T MRI. The effects of brain tissue segmentation and lesion detection rates were analyzed among single‐ and multispectral VBM variants. MP2‐single‐contrast gave better delineation of deep, subcortical nuclei but was prone to misclassification of dura/vessels as gray matter, even more than conventional‐T1. The addition of multispectral combinations (INV1, INV2, or FLAIR) could markedly reduce such misclassifications. MP2 + INV1 yielded generally clearer gray matter segmentation allowing better differentiation of white matter and neighboring gyri. Different models detected known lesions with a sensitivity between 60 and 100%. In non lesional cases, MP2 + INV1 was found to be best with a concordant rate of 37.5%, specificity of 51.6% and concordant to discordant ratio of 0.60. In summary, we show that multispectral MP2RAGE VBM (e.g., MP2 + INV1, MP2 + INV2) can improve brain tissue segmentation and lesion detection in epilepsy.     

基于体素的形态测量法分析高功能孤独性障碍患儿的脑组织密度

目的 分析学龄孤独性障碍患儿脑组织密度.方法 对17例智能正常的孤独性障碍患儿(病例组)以及15名年龄、性别、智商与之相匹配的健康儿童(对照组)进行T1加权三维磁共振成像扫描,应用基于体素的形态测量法(VBM)比较两组脑灰质及脑白质密度的差异.结果 与对照组相比,孤独性障碍患儿右侧小脑前叶的脑灰质密度低.右前扣带回、右额中回区域的脑白质密度低,双侧顶下小叶、右缘上回、右中央后回、右颞上回、右小脑后叶、左楔前叶、左楔叶的脑灰质密度高(P<0.001).结论 智力正常的学龄孤独性障碍患儿脑组织密度异常明显,且部位广泛.     

Microstructural white matter changes and their relation to neuropsychological deficits in patients with juvenile myoclonic epilepsy

ObjectiveJuvenile myoclonic epilepsy (JME) is the most common idiopathic generalized epilepsy syndrome. Neuropsychological, electrophysiological, and neuroimaging studies have led to the hypothesis that JME is related to dysfunction of frontal brain regions and mainly frontal thalamocortical networks.MethodsWe investigated possible microstructural white matter abnormalities of 20 patients with JME as compared with 20 healthy control subjects using diffusion tensor imaging (DTI). We analyzed whole-head DTI scans without an a-priori hypothesis using Tract-Based Spatial Statistics (TBSS). To analyze associated gray matter changes, we applied voxel-based morphometry (VBM) to a 3D T1 magnetization prepared rapid gradient echo (MPRAGE) sequence. Neuropsychological testing and personality trait tests were performed to bridge the gap between structure and function.ResultsIn patients, DTI revealed microstructural white matter changes in anterior parts of the Corpus callosum, anterior parts of the cingulate gyrus, and widespread frontal white matter bilaterally as well as in anterior parts of the right thalamus, which were not accompanied by gray matter changes in VBM. Microstructural changes in the cingulum correlated with personality traits. Neuropsychological test results showed impaired attention and executive functions and reduced short-term memory in the patient group. Also, there was a tendency toward alexithymia and significantly higher scores on depression.SignificanceThe present study results showed neuropsychological deficits including frontal lobe cognitive performance and a tendency toward alexithymia as well as accompanying microstructural neuroimaging changes in patients with JME, which all point to alterations in frontal brain regions and frontal thalamocortical networks in these patients.     

Proton magnetic resonance spectroscopy of systemic lupus erythematosus involving the central nervous system

We examined 13 patients with neurological manifestations of systemic lupus erythematosus (SLE) based on previous and/or current neurological or psychotic episodes by magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) together with psychiatric and cognitive assessment. MRI was abnormal in 7 patients, showing high signal lesions in the white matter and/or cerebral atrophy. Proton MRS centred on white matter lesions in 5 patients showed a reduction in theN-acetyl aspartate creatine ratio compared with normal appearing white matter in the SLE group and in 10 healthy controls. This pattern of abnormality does not allow differentiation of SLE lesions from the chronic plaques occurring in multiple sclerosis. There was a very high incidence of current psychiatric morbidity in the SLE group, namely in 12 of the 13 patients. There was no correlation between the presence of current psychiatric involvement and/or cognitive dysfunction and abnormalities detected with MRI or MRS.     

Grey and white matter loss along cerebral midline structures in myotonic dystrophy type 2

Abstract   Myotonic dystrophy type 2 (DM2) is an autosomal dominantly inherited multisystemic disorder and a common cause of muscular dystrophy in adults. Although neuromuscular symptoms predominate, there is clinical and imaging evidence of cerebral involvement. We used voxel-based morphometry (VBM) based on T1-weighted magnetic resonance images to investigate brain morphology in 13 DM2 patients in comparison to 13 sex- and age-matched controls. Further, we employed novel computational surface-based methods that specifically assess callosal thickness. We found grey and white matter loss along cerebral midline structures in our patient group. Grey matter reductions were present in brainstem and adjacent hypothalamic and thalamic regions, while white matter was mainly reduced in corpus callosum. The reduced callosal size was highly significant and independently confirmed by different methods. Our data provide first evidence for grey and white matter loss along brain midline structures in DM2 patients. The reduced size of the corpus callosum further extends the spectrum of white matter changes in DM2 and may represent the morphological substrate of neuropsychological abnormalities previously described in this disorder.     

Distinct white matter abnormalities in different idiopathic generalized epilepsy syndromes

Purpose: By definition idiopathic generalized epilepsy (IGE) is not associated with structural abnormalities on conventional magnetic resonance imaging (MRI). However, recent quantitative studies suggest white and gray matter alterations in IGE. The purpose of this study was to investigate whether there are white and/or gray matter structural differences between controls and two subsets of IGE, namely juvenile myoclonic epilepsy (JME) and IGE with generalized tonic–clonic seizures only (IGE‐GTC). Methods: We assessed white matter integrity and gray matter volume using diffusion tensor tractography–based analysis of fractional anisotropy and voxel‐based morphometry, respectively, in 25 patients with IGE, all of whom had experienced generalized tonic–clonic convulsions. Specifically, 15 patients with JME and 10 patients with IGE‐GTC were compared to two groups of similarly matched controls separately. Correlations between total lifetime generalized tonic–clonic seizures and fractional anisotropy were investigated for both groups. Key Findings: Tractography revealed lower fractional anisotropy in specific tracts including the crus of the fornix, body of corpus callosum, uncinate fasciculi, superior longitudinal fasciculi, anterior limb of internal capsule, and corticospinal tracts in JME with respect to controls, whereas there were no fractional anisotropy differences in IGE‐GTC. No correlation was found between fractional anisotropy and total lifetime generalized tonic–clonic seizures for either JME or IGE‐GTC. Although false discovery rate–corrected voxel‐based morphometry (VBM) showed no gray matter volume differences between patient and control groups, spatial extent cluster–corrected VBM analysis suggested a trend of gray matter volume reduction in frontal and central regions in both patient groups, more lateral in JME and more medial in IGE‐GTC. Significance: The findings support the idea that the clinical syndromes of JME and IGE‐GTC have unique anatomic substrates. The fact that the primary clinical difference between JME and IGE‐GTC is the occurrence of myoclonus in the former raises the possibility that disruption of white matter integrity may be the underlying mechanism responsible for myoclonus in JME. The cross‐sectional study design and relatively small number of subjects limits the conclusions that can be drawn here; however, the absence of a correlation between fractional anisotropy and lifetime seizures is suggestive that the white matter abnormalities observed in JME may not be secondary to seizures.