White matter abnormalities in early-onset schizophrenia: a voxel-based diffusion tensor imaging study

OBJECTIVE: To investigate abnormalities in the structural integrity of brain white matter as suggested by diffusion tensor imaging in adolescents with early-onset schizophrenia (onset of psychosis by age 18). METHOD: Twenty-six patients with schizophrenia and 34 age- and gender-matched healthy volunteers received diffusion tensor imaging and structural magnetic resonance imaging examinations. Fractional anisotropy maps were compared between groups in the white matter using a voxelwise analysis after intersubject registration to Talairach space. RESULTS: Compared with healthy volunteers, patients demonstrated lower fractional anisotropy values in the left anterior cingulate region in close proximity to the caudate nucleus (95% confidence interval of schizophrenic-healthy: -66 to -20). Using regression analysis, the rate of change in fractional anisotropy differed significantly between groups in this region across the age span examined (10-20 years), after adjusting for group differences in premorbid intellectual capacity and parental socioeconomic status. There were no areas of significantly higher fractional anisotropy in patients compared with healthy volunteers. CONCLUSIONS: These data suggest that early-onset schizophrenia is associated with a disruption in the structural integrity of white matter tracts in the anterior cingulate region. These structural abnormalities may contribute to the deficits in motivation, attention, memory, and higher executive functions in adolescents with schizophrenia.     

Altered cingulate white matter connectivity in panic disorder patients

OBJECTIVE: Functional imaging studies of panic disorder subjects suggest an increased activation of the cingulate regions of the brain. Aim of the current study was to explore the white matter connectivity differences between subjects with panic disorder and healthy comparison subjects. METHOD: Structural white matter connectivity, as determined from fractional anisotropy (FA) values obtained by diffusion tensor imaging, was assessed for anterior and posterior cingulate regions in 24 panic disorder patients and 24 age and sex-matched healthy comparison subjects. RESULTS: Subjects with panic disorder exhibited significantly greater FA values in left anterior and right posterior cingulate regions (by 13.3% and 19.6%, respectively) relative to comparison subjects. White matter connectivity for these two cingulate regions was also positively correlated with clinical severity, as determined by Panic Disorder Severity Scale. FA values in left anterior cingulate region negatively correlated with the time of Trail Making Tests and positively with Digit Symbol Substitution Test. CONCLUSIONS: Findings suggest a potential 'enhancement' in white matter connectivity in left anterior and right posterior cingulate regions in panic disorder, and that these changes may play an important role in mediating clinical symptoms of panic disorder.     

White matter integrity alterations in post‐traumatic stress disorder

Post‐traumatic stress disorder (PTSD) is a debilitating condition which can develop after exposure to traumatic stressors. Seventy‐five adults were recruited from the community, 25 diagnosed with PTSD along with 25 healthy and 25 trauma‐exposed age‐ and gender‐matched controls. Participants underwent clinical assessment and magnetic resonance imaging. A previous voxel based morphometry (VBM) study using the same subject cohort identified decreased grey matter (GM) volumes within frontal/subcortical brain regions including the hippocampus, amygdala, and anterior cingulate cortex (ACC). This study examines the microstructural integrity of white matter (WM) tracts connecting the aforementioned regions/structures. Using diffusion tensor imaging, we investigated the integrity of frontal/subcortical WM tracts between all three subject groups. Trauma exposed subjects with and without PTSD diagnosis were identified to have significant disruption in WM integrity as indexed by decreased fractional anisotropy (FA) in the uncinate fasciculus (UF), cingulum cingulate gyrus (CCG), and corpus callosum (CC), when compared with healthy non‐trauma‐exposed controls. Significant negative correlations were found between total Clinician Administered PTSD scale (CAPS) lifetime clinical subscores and FA values of PTSD subjects in the right UF, CCG, CC body, and right superior longitudinal fasciculus (SLF). An analysis between UF and SLF FA values and VBM determined rostral ACC GM values found a negative correlation in PTSD subjects. Findings suggest that compromised WM integrity in important tracts connecting limbic structures such as the amygdala to frontal regions including the ACC (i.e., the UF and CCG) may contribute to impairments in threat/fear processing associated with PTSD.     

Correlation between white matter damage and gray matter lesions in multiple sclerosis patients

We observed the characteristics of white matter fibers and gray matter in multiple sclerosis patients, to identify changes in diffusion tensor imaging fractional anisotropy values following white matter fiber injury. We analyzed the correlation between fractional anisotropy values and changes in whole-brain gray matter volume. The participants included 20 patients with relapsing-remitting multiple sclerosis and 20 healthy volunteers as controls. All subjects underwent head magnetic resonance imaging and diffusion tensor imaging. Our results revealed that fractional anisotropy values decreased and gray matter volumes were reduced in the genu and splenium of corpus callosum, left anterior thalamic radiation, hippocampus, uncinate fasciculus, right corticospinal tract, bilateral cingulate gyri, and inferior longitudinal fasciculus in multiple sclerosis patients. Gray matter volumes were significantly different between the two groups in the right frontal lobe(superior frontal, middle frontal, precentral, and orbital gyri), right parietal lobe(postcentral and inferior parietal gyri), right temporal lobe(caudate nucleus), right occipital lobe(middle occipital gyrus), right insula, right parahippocampal gyrus, and left cingulate gyrus. The voxel sizes of atrophic gray matter positively correlated with fractional anisotropy values in white matter association fibers in the patient group. These findings suggest that white matter fiber bundles are extensively injured in multiple sclerosis patients. The main areas of gray matter atrophy in multiple sclerosis are the frontal lobe, parietal lobe, caudate nucleus, parahippocampal gyrus, and cingulate gyrus. Gray matter atrophy is strongly associated with white matter injury in multiple sclerosis patients, particularly with injury to association fibers.     

Reduced structural connectivity of a major frontolimbic pathway in generalized anxiety disorder

CONTEXT Emotion regulation deficits figure prominently in generalized anxiety disorder (GAD) and in other anxiety and mood disorders. Research examining emotion regulation and top-down modulation has implicated reduced coupling of the amygdala with prefrontal cortex and anterior cingulate cortex, suggesting altered frontolimbic white matter connectivity in GAD. OBJECTIVES To investigate structural connectivity between ventral prefrontal cortex or anterior cingulate cortex areas and the amygdala in GAD and to assess associations with functional connectivity between those areas. DESIGN Participants underwent diffusion-tensor imaging and functional magnetic resonance imaging. SETTING University magnetic resonance imaging facility. PARTICIPANTS Forty-nine patients with GAD and 39 healthy volunteer control subjects, including a matched subset of 21 patients having GAD without comorbid Axis I diagnoses and 21 healthy volunteers matched for age, sex, and education. MAIN OUTCOME MEASURES The mean fractional anisotropy values in the left and right uncinate fasciculus, as measured by tract-based analysis for diffusion-tensor imaging data. RESULTS Lower mean fractional anisotropy values in the bilateral uncinate fasciculus indicated reduced frontolimbic structural connectivity in patients with GAD. This reduction in uncinate fasciculus integrity was most pronounced for patients without comorbidity and was not observed in other white matter tracts. Across all participants, higher fractional anisotropy values were associated with more negative functional coupling between the pregenual anterior cingulate cortex and the amygdala during the anticipation of aversion. CONCLUSIONS Reduced structural connectivity of a major frontolimbic pathway suggests a neural basis for emotion regulation deficits in GAD. The functional significance of these structural differences is underscored by decreased functional connectivity between the anterior cingulate cortex and the amygdala in individuals with reduced structural integrity of the uncinate fasciculus.     

Anterior cingulate, gyrus rectus, and orbitofrontal abnormalities in elderly depressed patients: an MRI-based parcellation of the prefrontal cortex

OBJECTIVE: To examine structural abnormalities in subregions of the prefrontal cortex in elderly patients with depression, the authors explored differences in gray matter, white matter, and CSF volumes by applying a parcellation method based on magnetic resonance imaging (MRI). METHOD: Twenty-four elderly patients with major depression and 19 group-matched comparison subjects were studied with high-resolution MRI. Cortical surface extraction, tissue segmentation, and cortical parcellation methods were applied to obtain volume measures of gray matter, white matter, and CSF in seven prefrontal subregions: the anterior cingulate, gyrus rectus, orbitofrontal cortex, precentral gyrus, superior frontal cortex, middle frontal cortex, and inferior frontal cortex. RESULTS: Highly significant bilateral volume reductions in gray matter were observed in the anterior cingulate, the gyrus rectus, and the orbitofrontal cortex. Depressed patients also exhibited significant bilateral white matter volume reductions and significant CSF volume increases in the anterior cingulate and the gyrus rectus. Finally, the depressed group showed significant CSF volume reductions in the orbitofrontal cortex relative to the comparison subjects. None of the other regions examined revealed significant structural abnormalities. CONCLUSIONS: The prominent bilateral gray matter deficits in the anterior cingulate and the gyrus rectus as well as the orbitofrontal cortex may reflect disease-specific modifications of elderly depression. The differential pattern of abnormalities detected in the white matter and CSF compartments imply that distinct etiopathological mechanisms might underlie the structural cortical changes in these regions.     

Frontal white matter anisotropy and symptom severity of late-life depression: a magnetic resonance diffusion tensor imaging study

OBJECTIVES: To investigate the disruption of neural circuits in the frontal lobes and limbic structures in late-life depressed patients compared with healthy controls, and to examine the correlation between the degree of microstructural abnormalities of white matter and clinical symptom severity in late-life depression. METHODS: Thirteen patients with late-life depression and matched control subjects underwent diffusion tensor imaging. Fractional anisotropy (FA), an index of the integrity of white matter tracts, was determined in the white matter of frontal, temporal, and occipital brain regions and the corpus callosum. RESULTS: A significant reduction was found in white matter FA values of widespread regions of the frontal and temporal lobes of depressed patients. Also, there was some evidence suggesting that white matter FA values of the inferior frontal brain region are inversely related to severity of depression. CONCLUSIONS: These results suggest the possible loss of integrity within frontal and temporal white matter fibre tracts and implicate the orbitofrontal circuit in symptom severity in late-life depression.     

Frontal lobe gray matter density decreases in bipolar I disorder.

BACKGROUND: This study was conducted to explore differences in gray and white matter density between bipolar and healthy comparison groups using voxel-based morphometry (VBM). METHODS: Brain magnetic resonance imaging was performed for 39 subjects with bipolar I disorder and 43 comparison subjects. Images were registered into a proportional stereotaxic space and segmented into gray matter, white mater, and cerebrospinal fluid. Statistical parametric mapping was used to calculate differences in gray and white matter density between groups. RESULTS: Bipolar subjects had decreased gray matter density in left anterior cingulate gyrus (Brodmann's area [BA] 32, 7.3% decrease), an adjacent left medial frontal gyrus (BA 10, 6.9% decrease), right inferior frontal gyrus (BA 47, 9.2% decrease), and right precentral gyrus (BA 44, 6.2% decrease), relative to comparison subjects. CONCLUSIONS: The observation of a gray matter density decrease in the left anterior cingulate, which processes emotions, in bipolar subjects is consistent with prior reports that used region-of-interest analytic methods. Decreased gray matter density in the right inferior frontal gyrus, which processes nonverbal and intrinsic functions, supports nondominant hemisphere dysfunction as a component of bipolar disorder.     

药物过度使用性头痛患者脑白质结构的变化

目的利用磁共振弥散张量成像技术研究药物过度使用性头痛患者脑白质结构的变化。方法药物过度使用性头痛患者(病例组)及年龄、性别相匹配的同期健康体检者(对照组)各80例,收集一般临床资料,进行颅脑磁共振弥散张量成像(diffusion tensor imaging,DTI)检查,测取部分各向异性(fractional anisotropy,FA)值、表观弥散系数(apparent diffusion coefficient,ADC)值,并结合临床特点进行相关性分析。结果 (1)病例组眶额皮质、前后扣带回皮质、胼胝体压部、右侧内囊前肢FA值较对照组明显降低,差异有统计学意义(P0.05);(2)病例组右侧眶额皮质、左侧额下回皮质及前扣带回皮质ADC值较对照组明显升高,差异有统计学意义(P0.05);(3)病例组双侧眶额部皮质以及右侧内囊后肢FA值与患者头痛病程及发作频率呈负相关;左侧内囊后肢FA值与头痛频率呈负相关;(4)病例组左侧眶额皮质ADC值与患者头痛病程及发作频率呈正相关;右侧眶额皮质以及前扣带回皮质ADC值与患者头痛发作频率呈正相关;后扣带回皮质ADC值与患者头痛病程呈正相关。结论药物过度使用性头痛患者双侧额叶皮质及扣带回皮质存在白质微观结构异常变化,FA值与患者头痛病程及发作频率呈负相关,ADC值则呈正相关。     

Frontal white matter integrity in borderline personality disorder with self-injurious behavior

Self-injurious behavior in borderline personality disorder is a frequent cause of morbidity and mortality, but neurobiological studies examining this behavior are few. Nine women with borderline personality disorder self-injurious behavior and seven comparison subjects underwent diffusion tensor imaging (DTI). Trace and fractional anisotropy (FA) were calculated for frontal and posterior regions. Borderline personality disorder-self-injurious behavior subjects also underwent a battery of neuropsychological tests that emphasized executive functions. They had significantly higher trace and lower FA in inferior frontal but not posterior regions. Correlational analyses between DTI and cognitive variables showed a pattern of results that was contrary to expectations with posterior white matter integrity correlating with isolated measures of executive function and anterior white matter integrity correlating with a component of verbal memory test performance. Women with borderline personality disorder-self-injurious behavior exhibit decreased white matter microstructural integrity in inferior frontal brain regions that may include components of orbito-frontal circuitry.     

Dorsolateral Prefrontal Cortex and Anterior Cingulate Cortex White Matter Alterations in Late-Life Depression

BACKGROUND: The dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) are critical for mood regulation. Alterations in the white matter connections of these regions may impair their role in mood regulation and increase the risk of developing depression. This study used diffusion tensor imaging to examine for white matter microstructural abnormalities of these regions and of central white matter structures in late-life depression. METHODS: One hundred six elderly depressed subjects and eighty-four elderly nondepressed subjects underwent clinical assessment and diffusion tensor imaging. The apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in regions of interest placed in the white matter of the DLPFC, ACC, corpus callosum, and internal capsule. Differences between groups were assessed, controlling for age, sex, and total cerebral volume. RESULTS: After controlling for covariates, depressed subjects had significantly lower FA values in white matter of the right ACC, bilateral superior frontal gyri, and left middle frontal gyrus. There were no significant differences in ADC values. CONCLUSIONS: Lower FA, representing lower tissue organization, is observed in depressed elders in the DLPFC and right ACC. These findings support the hypothesis that altered connectivity between brain regions contributes to the risk of depression.     

A proton MRSI study of brain N-acetylaspartate level after 12 weeks of citalopram treatment in drug-naive patients with obsessive-compulsive disorder

OBJECTIVE: Reductions in the level of N-acetylaspartate within subcortical structures of patients with obsessive-compulsive disorder (OCD) have been reported in several studies. However, there have been, as yet, no reports regarding N-acetylaspartate levels in the prefrontal cortex of adult drug-naive OCD patients. The authors used proton magnetic resonance spectroscopic imaging ((1)H-MRSI) to investigate regional N-acetylaspartate level abnormalities and changes after 12 weeks of pharmacotherapy with citalopram in drug-naive OCD patients. METHOD: Thirteen drug-naive OCD patients and 13 age- and sex-matched healthy comparison subjects were included in this study. N-acetylaspartate levels (obtained from ratios of N-acetylaspartate with creatine, choline, and creatine plus choline) in the prefrontal cortex, parietal cortex, anterior cingulate, posterior cingulate, frontal white matter, and parietal white matter were measured by (1)H-MRSI. In OCD patients, measurements were taken before and after 12 weeks of citalopram treatment. Correlations between N-acetylaspartate concentrations in regions of interest and clinical measures were also assessed. RESULTS: Drug-naive OCD patients exhibited significantly lower N-acetylaspartate levels in the prefrontal cortex, frontal white matter, and anterior cingulate at baseline than did comparison subjects. Significant increases in N-acetylaspartate level were detected in the prefrontal cortex and frontal white matter in OCD patients after 12 weeks of citalopram treatment. CONCLUSIONS: These data suggest that reductions in neuronal viability occur in the frontal region of OCD patients and that these reductions may be partly reversible.     

White matter abnormalities in obsessive-compulsive disorder: a diffusion tensor imaging study

CONTEXT: Several neurobiological models of obsessive-compulsive disorder (OCD) posit a primary role for dysfunction of the anterior cingulate gyrus. Both functional and structural neuroimaging studies have implicated anterior cingulate gray matter abnormalities in the pathophysiology of OCD, but there has been little investigation of the anterior cingulate white matter in this disorder. OBJECTIVE: To test the hypothesis that patients with OCD have abnormal white matter microstructure in the anterior cingulate gyrus compared with healthy volunteers as inferred from diffusion tensor imaging. Additional analyses examined group differences in white matter integrity across the entire brain. DESIGN, SETTING, AND PARTICIPANTS: Fifteen patients with a DSM-IV diagnosis of OCD and 15 healthy volunteers matched for age, sex, and handedness underwent diffusion tensor imaging and structural magnetic resonance imaging examinations. Fractional anisotropy (FA), a robust intravoxel measure of water self-diffusion, was compared between groups on a voxel-by-voxel basis in the anterior cingulate white matter after standardization in Talairach space. MAIN OUTCOME MEASURES: Clinical ratings of symptom severity (ie, Yale-Brown Obsessive-Compulsive Scale) and FA. RESULTS: Compared with healthy volunteers, patients demonstrated significantly lower FA bilaterally in 3 areas of the anterior cingulate gyrus white matter. Additional analyses conducted across the rest of the brain white matter revealed lower FA bilaterally in the parietal region (supramarginal gyri), right posterior cingulate gyrus, and left occipital lobe (lingual gyrus). No areas of significantly higher FA were observed in patients compared with healthy volunteers. Lower FA in the parietal region correlated significantly with higher Yale-Brown Obsessive-Compulsive Scale scores. CONCLUSIONS: These preliminary findings provide evidence of an abnormality that involves the anterior cingulate white matter in the pathogenesis of OCD and are consistent with neurobiological models that posit a defect in connectivity in the anterior cingulate basal ganglia-thalamocortical circuit. White matter abnormalities in other brain regions may also be implicated in the neurobiology of OCD.     

The effect of meditation on brain structure: cortical thickness mapping and diffusion tensor imaging

A convergent line of neuroscientific evidence suggests that meditation alters the functional and structural plasticity of distributed neural processes underlying attention and emotion. The purpose of this study was to examine the brain structural differences between a well-matched sample of long-term meditators and controls. We employed whole-brain cortical thickness analysis based on magnetic resonance imaging, and diffusion tensor imaging to quantify white matter integrity in the brains of 46 experienced meditators compared with 46 matched meditation-naïve volunteers. Meditators, compared with controls, showed significantly greater cortical thickness in the anterior regions of the brain, located in frontal and temporal areas, including the medial prefrontal cortex, superior frontal cortex, temporal pole and the middle and interior temporal cortices. Significantly thinner cortical thickness was found in the posterior regions of the brain, located in the parietal and occipital areas, including the postcentral cortex, inferior parietal cortex, middle occipital cortex and posterior cingulate cortex. Moreover, in the region adjacent to the medial prefrontal cortex, both higher fractional anisotropy values and greater cortical thickness were observed. Our findings suggest that long-term meditators have structural differences in both gray and white matter.     

Disrupted white matter tract integrity of anterior cingulate in trauma survivors

The objective of this study was to examine the integrity of whole-brain white matter in posttraumatic stress disorder patients. Twenty posttraumatic stress disorder patients who survived the Taegu subway fire incident and 20 healthy volunteers participated in this study. Statistical parametric mapping was used to evaluate the global differences in fractional anisotropy values between the two groups. The results show that posttraumatic stress disorder patients had significantly lower fractional anisotropy values in the left anterior cingulate regions. Posttraumatic stress disorder symptom severity negatively correlated to the level of decrease in anterior cingulate fractional anisotropy values. The outcome of the current study suggests that the disruption of the left anterior cingulate white matter tract integrity may play an important role in the pathophysiology of posttraumatic stress disorder.     

Brain structural abnormalities in psychotropic drug-naive pediatric patients with obsessive-compulsive disorder

OBJECTIVE: The authors investigated structural abnormalities in brain regions comprising cortical-striatal-thalamic-cortical loops in pediatric patients with obsessive-compulsive disorder (OCD). METHOD: Volumes of the caudate nucleus, putamen, and globus pallidus and gray and white matter volumes of the anterior cingulate gyrus and superior frontal gyrus were computed from contiguous 1.5-mm magnetic resonance images from 23 psychotropic drug-naive pediatric patients with OCD (seven male patients and 16 female patients) and 27 healthy volunteers (12 male subjects and 15 female subjects). RESULTS: Patients had smaller globus pallidus volumes than healthy volunteers, but the two groups did not differ in volumes of the caudate nucleus, putamen, or frontal white matter regions. Compared to healthy volunteers, patients had more total gray matter in the anterior cingulate gyrus but not the superior frontal gyrus. Total anterior cingulate gyrus volume correlated significantly and positively with globus pallidus volume in the healthy volunteers but not in patients. CONCLUSIONS: These findings provide evidence of smaller globus pallidus volume in patients with OCD without the potentially confounding effects of prior psychotropic drug exposure. Volumetric abnormalities in the anterior cingulate gyrus appear specific to the gray matter in OCD, at least at the gross anatomic level, and are consistent with findings of functional neuroimaging studies that have reported anterior cingulate hypermetabolism in the disorder.     

Frontal white matter biochemical abnormalities in late-life major depression detected with proton magnetic resonance spectroscopy

OBJECTIVE: Neuroanatomical abnormalities have been identified in patients with late-life mood disorders by using magnetic resonance imaging. This study examined the biochemical correlates of late-life major depression in the frontal gray and white matter by using single-voxel proton spectroscopy. METHOD: Twenty elderly patients with major depression and 18 comparison subjects similar in age and gender to the patients were scanned on a 1.5-T magnetic resonance scanner with head coil. Voxels were placed in the left dorsolateral white matter and bilaterally in the anterior cingulate gray matter. Absolute levels of N-acetylaspartate, choline, myo-inositol, and creatine were estimated with the LC-Model algorithm. Ratios of metabolite to creatine levels were computed from the absolute values. RESULTS: myo-Inositol/creatine and choline/creatine ratios were significantly higher in the frontal white matter in the major depression group than in the comparison group. The groups had no significant differences in the metabolite ratios in the gray matter. CONCLUSIONS: Biochemical changes in the white matter may provide some of the neurobiological substrates to late-life major depression.     

未经治疗的抑郁症首次发病患者脑弥散张量成像的研究

目的 通过对未经治疗的抑郁症首次发病(以下简称首发)患者进行弥散张最成像(DTI)检查,探讨抑郁症患者脑门质的完整性及其与病程和抑郁严重程度的相关性.方法 对17名首发末服药抑郁症患者(以下简称患者组)和17名年龄、性别和文化程度相匹配的健康对照(以下简称对照组)进行全脑DTI扫描.以基于体素的分析比较两组受试者脑白质的分数各向异性(FA)的差异.提取差异有统计学意义的脑区的FA绝对值,将其与汉密尔顿抑郁量表(17项,HAMD)总分和患者病程进行相关分析.结果 患者组的双侧额中回、左侧扣带回和颞下回白质的FA值显著低于对照组(P＜0.01,cluster＞100).右侧额中回的FA值与病程呈显著负相关(r=-0.732,P=0.001).未发现各脑区的FA值与HAMD总分存在相关.结论脑白质完整性异常可能是抑郁症的生物学特征之一,抑郁症病程对脑白质的完整性有明显影响.     

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.