Transcranial magnetic stimulation shows impaired transcallosal inhibition in Marchiafava–Bignami syndrome

A case of Marchiafava–Bignami (MB) syndrome with selective callosal involvement was evaluated by clinical examination and magnetic resonance imaging (MRI) in the acute phase and 6 months after the onset of symptoms; at the same time, the corticospinally and transcallosally mediated effects elicited by transcranial magnetic stimulation (TMS) were investigated. The first MRI study showed the presence of extensive abnormal signal intensity throughout the entire corpus callosum. After high-dose corticosteroid administration her symptoms rapidly resolved, in parallel with the reversion of MRI changes, except for severe cognitive impairment. Follow-up TMS examination revealed persistent transcallosal inhibition (TI) abnormalities. This report indicates that the measurement of TI during the course of MB syndrome is useful for evaluating functional changes to the corpus callosum, including their evaluation with time and after treatment and for elucidating the pathophysiology of MB syndrome.     

Callosal degeneration topographically correlated with cognitive function in amnestic mild cognitive impairment and alzheimer's disease dementia

Degeneration of the corpus callosum (CC) is evident in the pathogenesis of Alzheimer's disease (AD). However, the correlation of microstructural damage in the CC on the cognitive performance of patients with amnestic mild cognitive impairment (aMCI) and AD dementia is undetermined. We enrolled 26 normal controls, 24 patients with AD dementia, and 40 single‐domain aMCI patients with at least grade 1 hippocampal atrophy and isolated memory impairment. Diffusion tensor imaging (DTI) with fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (DA), and radial diffusivity (DR) were measured. The entire CC was parcellated based on fiber trajectories to specific cortical Brodmann areas using a probabilistic tractography method. The relationship between the DTI measures in the subregions of the CC and cognitive performance was examined. Although the callosal degeneration in the patients with aMCI was less extended than in the patients with AD dementia, degeneration was already exhibited in several subregions of the CC at the aMCI stage. Scores of various neuropsychological tests were correlated to the severity of microstructural changes in the subregional CC connecting to functionally corresponding cortical regions. Our results confirm that CC degeneration is noticeable as early as the aMCI stage of AD and the disconnection of the CC subregional fibers to the corresponding Brodmann areas has an apparent impact on the related cognitive performance. Hum Brain Mapp 35:1529–1543, 2014. © 2013 Wiley Periodicals, Inc.     

Measurements of transcallosally mediated cortical inhibition for differentiating parkinsonian syndromes.

Clinicopathologic evidence suggests differential involvement of cortex and corpus callosum (CC) in various disorders presenting with a parkinsonian syndrome. We tested the hypothesis of whether neurophysiologic and morphometric assessments of CC as surrogate parameters of cortical involvement could be helpful in differential diagnosis of parkinsonian disorders. The integrity of CC was assessed neurophysiologically by measuring the ipsilateral silent period (iSP) evoked by transcranial magnetic stimulation (TMS) in a total of 25 patients with idiopathic parkinsonian syndromes (IPS), corticobasal ganglionic degeneration (CBD), progressive supranuclear palsy (PSP), or multiple system atrophy (MSA). Additionally, morphometric analyses of magnetic resonance imaging (MRI) measurements of CC was carried out in all patients. iSP was abnormal in all 5 CBD and all 5 PSP patients, whereas it was intact in all 10 IPS patients and all 5 MSA patients. Among various MRI parameters of CC, testing between different groups revealed a significant difference only for measurements of the middle part of the truncus. CBD and PSP patients exhibited a significant atrophy as compared with control subjects. These data suggest impairment of callosal integrity in patients with CBD and PSP. iSP measurements may be a useful clinical neurophysiologic test in differential diagnosis of patients with parkinsonian syndromes.     

Involvement of motor pathways in corticobasal syndrome detected by diffusion tensor tractography

Corticobasal syndrome (CBS) is a progressive parkinsonian disease characterized by cortical and subcortical neuronal loss. Although motor disabilities are a core feature of CBS, the involvement of motor pathways in this condition has not been completely clarified. We used magnetic resonance diffusion tensor imaging (DTI) to study corticospinal and transcallosal motor projections in CBS, and applied fiber tractography to analyze the axonal integrity of white matter projections. Ten patients with CBS were compared with 10 age‐matched healthy controls. Fiber tracts were computed using a Monte‐Carlo simulation approach. Tract‐specific mean values of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were determined. CBS patients showed a reduction of corticospinal tract (CST) fibers on the first affected side with significantly increased ADC and reduced FA values. In the corpus callosum (CC), particularly in the posterior trunk, patients also had significantly reduced fiber projections, with a higher ADC and lower FA than controls. This pattern indicates changes of the white matter integrity in both CST and CC. Thus, magnetic resonance DTI can be used to assess motor pathway involvement in CBS patients. © 2008 Movement Disorder Society     

Motor callosal disconnection in early relapsing-remitting multiple sclerosis

In relapsing-remitting multiple sclerosis (RRMS) the corpus callosum (CC) is often and early affected by macroscopic lesions when investigated by conventional MRI. We sought to determine to which extent microstructural and effective disconnection of the CC are already present in RRMS patients at the earliest stages of the disease prior to evidence of macroscopic CC lesion. We compared 16 very early RRMS patients (median expanded disability status scale (EDSS), 1.5; range, 0-2.0) to an age-matched group of healthy controls and focused analysis to the motor CC, i.e. that part of the CC relaying interhemispheric motor information. A combined functional magnetic resonance imaging/diffusion tensor imaging fiber-tracking procedure was applied to identify the callosal motor fibers (CMFs) connecting the hand areas of the primary motor cortices of the two hemispheres. Fractional anisotropy (FA) within the motor CC (FA-CC) assessed the CMF microstructural integrity. Bifocal paired transcranial magnetic stimulation (TMS) tested short-interval interhemispheric inhibition (S-IHI), an established measure of CMF effective connectivity. FA-CC and S-IHI were significantly reduced in early RRMS compared to healthy controls. Furthermore, a significant linear correlation between microstructure (FA-CC) and function (S-IHI) in the controls was broken down in the patients. These abnormalities were obtained in the absence of macroscopic CMF lesion in conventional MRI, and whilst motor hand/arm function in the nine-hole-peg test and corticospinal conduction time were normal. Findings suggest that reductions in FA and S-IHI may serve as surrogate markers of motor callosal disconnection at the earliest stages of RRMS prior to development of macroscopic lesion.     

“Ears of the Lynx” Sign in a Marchiafava–Bignami patient: Structural Basis and Fiber‐Tracking DTI Contribution to the Understanding of this Imaging Abnormality

The “ears of the lynx” sign was previously reported as a neuroimaging finding observed in patients with autosomal recessive hereditary spastic paraplegia in association with a thin corpus callosum (ARHSP–TCC). We report a patient with a chronic form of Marchiafava–Bignami disease (MBD) that presented with this imaging feature. Diffusion tensor imaging (DTI) and fiber‐tracking data support that this finding is a consequence of the structural derangement, which enlarges a preexisting border zone of the bundles of fibers from the corpus callosum (CC) genu to the forceps minor and anterior corona radiata. Therefore, we assume that despite their pathological differences, damage to the anterior portion of the CC is responsible for the imaging similarities between MBD and ARHSP–TCC.     

Interhemispheric motor networks are abnormal in patients with Gilles de la Tourette syndrome

Brain imaging has shown altered corpus callosum (CC) morphology in patients with Gilles de la Tourette syndrome (GTS). Yet it is unclear whether these morphological changes are associated with altered interhemispheric interactions. Here, we combined transcranial magnetic stimulation (TMS) with diffusion tensor magnetic resonance imaging (DTI) to explore functional and structural interhemispheric connections between the left and right motor hand areas. We studied 14 unmedicated GTS patients without psychiatric comorbidity (2 women, mean age 35.5 years) and 15 healthy volunteers (3 women, mean age 35 years). Left‐to‐right and right‐to‐left interhemispheric inhibitions (IHIs) were measured in hand muscles with TMS. In 13 GTS patients and all healthy controls, we measured fractional anisotropy (FA) with DTI to examine the relation between functional measures of interhemispheric connectivity as derived by TMS and structural properties of the CC region that carries fibers interconnecting both motor cortices. In GTS patients, left‐to‐right IHI was weaker than right‐to‐left IHI. Left‐to‐right IHI in GTS patients was also reduced compared with healthy controls. Voxel‐based morphometric analysis revealed that FA in the motor region of the CC did not differ between groups. However, there was a significant interaction between groups and the relation between regional FA and left‐to‐right IHI in the motor region of the CC. A negative linear relation between FA and left‐to‐right IHI was present in control subjects but not in patients. Our combined TMS‐DTI approach demonstrates abnormal functional interhemispheric connectivity in GTS accompanied by an altered structure–function relationship in the motor CC. © 2010 Movement Disorder Society.     

Diffusion Tensor Tractography Analysis of the Corpus Callosum Fibers in Amyotrophic Lateral Sclerosis

Background and Purpose

Involvement of the corpus callosum (CC) is reported to be a consistent feature of amyotrophic lateral sclerosis (ALS). We examined the CC pathology using diffusion tensor tractography analysis to identify precisely which fiber bundles are involved in ALS.

Methods

Diffusion tensor imaging was performed in 14 sporadic ALS patients and 16 age-matched healthy controls. Whole brain tractography was performed using the multiple-region of interest (ROI) approach, and CC fiber bundles were extracted in two ways based on functional and structural relevance: (i) cortical ROI selection based on Brodmann areas (BAs), and (ii) the sulcal-gyral pattern of cortical gray matter using FreeSurfer software, respectively.

Results

The mean fractional anisotropy (FA) values of the CC fibers interconnecting the primary motor (BA4), supplementary motor (BA6), and dorsolateral prefrontal cortex (BA9/46) were significantly lower in ALS patients than in controls, whereas those of the primary sensory cortex (BA1, BA2, BA3), Broca''s area (BA44/45), and the orbitofrontal cortex (BA11/47) did not differ significantly between the two groups. The FreeSurfer ROI approach revealed a very similar pattern of abnormalities. In addition, a significant correlation was found between the mean FA value of the CC fibers interconnecting the primary motor area and disease severity, as assessed using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale, and the clinical extent of upper motor neuron signs.

Conclusions

Our findings suggest that there is some degree of selectivity or a gradient in the CC pathology in ALS. The CC fibers interconnecting the primary motor and dorsolateral prefrontal cortices may be preferentially involved in ALS.     

Changes in callosal motor fiber integrity after subcortical stroke of the pyramidal tract

In the healthy brain, there are close correlations between task-related activation of the primary motor cortex (M1), the magnitude of interhemispheric inhibition, and microstructural properties of transcallosal fiber tracts. After subcortical stroke affecting the pyramidal tract (PT), an abnormal pattern of bilateral activity develops in M1. With this prospective longitudinal study, we aimed to determine whether a morphological correlate of poststroke disinhibition could be measured within 20 days and 6 months of PT stroke. Using diffusion tensor imaging with tractography, we delineated transcallosal motor fibers (CMF) in nine PT stroke patients, six patients with subcortical infarct not affecting the PT (NonPT) and six transient ischemic attack patients. We compared changes in CMF fractional anisotropy ratios (rFA) with rFA in a distinct bundle of callosal occipital fibers (COF). At the initial time point, there were no significant differences in rFA between groups and fiber bundles. At follow-up, PT-group rFA(CMF) was significantly lower than PT-group rFA(COF) and NonPT-group rFA(CMF). PT-group rFA(CMF) decreased over time and correlated with rFA of the PT (rFA(PT)) retrograde to the infarct at 6 months. Our data suggest a progressive degenerative transsynaptic effect of PT stroke on CMF, which could be a morphological correlate of transcallosal disinhibition.     

Modular‐level alterations of structure–function coupling in schizophrenia connectome

Convergent evidences have revealed that schizophrenia is associated with brain dysconnectivity, which leads to abnormal network organization. However, discrepancies were apparent between the structural connectivity (SC) and functional connectivity (FC) studies, and the relationship between structural and functional deficits in schizophrenia remains largely unknown. In this study, resting‐state functional magnetic resonance imaging and structural diffusion tensor imaging were performed in 20 patients with schizophrenia and 20 matched healthy volunteers (patients/controls = 19/17 after head motion rejection). Functional and structural brain networks were obtained for each participant. Graph theoretical approaches were employed to parcellate the FC networks into functional modules. The relationships between the entries of SC and FC were estimated within each module to identify group differences and their correlations with clinical symptoms. Although five common functional modules (including the default mode, occipital, subcortical, frontoparietal, and central modules) were identified in both groups, the patients showed a significantly reduced modularity in comparison with healthy participants. Furthermore, we found that schizophrenia‐related aberrations of SC–FC coupling exhibited complex patterns among modules. Compared with controls, patients showed an increased SC–FC coupling in the default mode and the central modules. Moreover, significant SC–FC decoupling was demonstrated in the occipital and the subcortical modules, which was associated with longer duration of illness and more severe clinical manifestations of schizophrenia. Taken together, these findings demonstrated that altered module‐dependent SC–FC coupling may underlie abnormal brain function and clinical symptoms observed in schizophrenia and highlighted the potential for using new multimodal neuroimaging biomarkers for diagnosis and severity evaluation of schizophrenia. Hum Brain Mapp 38:2008–2025, 2017. © 2017 Wiley Periodicals, Inc.