Increased grey matter volume and associated resting-state functional connectivity in chronic spontaneous urticaria: A structural and functional MRI study

Background and purposeChronic itch is one of the most common irritating sensations, yet its mechanisms have not been fully elucidated. Although some studies have revealed relationships between itching and brain function, the structural changes in the brain induced by chronic itching, such as those accompanying chronic spontaneous urticaria (CSU), remain unclear. In this study, we aimed to explore the potential changes in brain structure and the associated functional circuitry in CSU patients to generate insights to aid chronic itch management.MethodsForty CSU patients and forty healthy controls (HCs) were recruited. Seven-day urticaria activity score (UAS7) values were collected to evaluate clinical symptoms. Voxel-based morphometry (VBM) and seed-based resting-state functional connectivity (rs-FC) analysis were used to assess structural changes in the brain and associated changes in functional circuitry.ResultsCompared with HCs, CSU patients had significantly increased grey matter (GM) volume in the right premotor cortex, left fusiform cortex, and cerebellum. UAS7 values were positively associated with GM volume in the left fusiform cortex. In CSU patients relative to HCs, the left fusiform cortex as extracted by VBM analysis demonstrated decreased functional connectivity with the right orbitofrontal cortex, medial prefrontal cortex (mPFC), premotor cortex, primary motor cortex (MI), and cerebellum and increased functional connectivity with the right posterior insular cortex, primary somatosensory cortex (SI), and secondary somatosensory cortex (SII). The left cerebellum as extracted from VBM analysis demonstrated decreased functional connectivity with the right supplementary motor area (SMA) and MI in CSU patients relative to HCs.ConclusionsOur findings indicate that patients suffering from chronic itching conditions, such as CSU, are likely to demonstrate altered GM volume in some brain regions. These changes may affect not only the sensorimotor area but also brain regions associated with cognitive function.     

A multicentre study of motor functional connectivity changes in patients with multiple sclerosis

In this multicentre study involving eight European centres, we characterized the spatial pattern of functional connectivity (FC) in the sensorimotor network from 61 right-handed patients with multiple sclerosis (MS) and 74 age-matched healthy subjects assessed with the use of functional magnetic resonance imaging (fMRI) and a simple motor task of their right dominant hand. FC was investigated by using: (i) voxel-wise correlations between the left sensorimotor cortex (SMC) and any other area in the brain; and (ii) bivariate correlations between time series extracted from several regions of interest (ROIs) belonging to the sensorimotor network. Both healthy controls and MS patients had significant FC between the left SMC and several areas of the sensorimotor network, including the bilateral postcentral and precentral gyri, supplementary motor area, middle frontal gyri, insulae, secondary somatosensory cortices, thalami, and right cerebellum. Voxel-wise assessment of FC revealed increased connectivity between the left SMC and the right precentral gyrus, right middle frontal gyrus (MFG) and bilateral postcentral gyri in MS patients as compared with controls. ROI analysis also showed a widespread pattern of altered connectivity, characterized by increased FC between the right MFG, the left insula and the right inferior frontal gyrus in comparison with many regions of the sensorimotor network. These results provide further evidence for increased bihemispheric contributions to motor control in patients with MS relative to healthy controls. They further suggest that multicentre fMRI studies of FC changes are possible, and provide a potential imaging biomarker for use in experimental therapeutic studies directed at enhancing adaptive plasticity in the disease.     

Abnormal connectivity of the sensorimotor network in patients with MS: A multicenter fMRI study

In this multicenter study, we used dynamic causal modeling to characterize the abnormalities of effective connectivity of the sensorimotor network in 61 patients with multiple sclerosis (MS) compared with 74 age‐matched healthy subjects. We also investigated the correlation of such abnormalities with findings derived from structural MRI. In a subgroup of subjects, diffusion tensor (DT) MRI metrics of the corpus callosum and the left corticospinal tract (CST) were also assessed. MS patients showed increased effective connectivity relative to controls between: (a) the left primary SMC and the left dorsal premotor cortex (PMd), (b) the left PMd and the supplementary motor areas (SMA), (c) the left secondary sensorimotor cortex (SII) and the SMA, (d) the right SII and the SMA, (e) the left SII and the right SII, and (f) the right SMC and the SMA. MS patients had relatively reduced effective connectivity between the left SMC and the right cerebellum. No interaction was found between disease group and center. Coefficients of altered connectivity were weakly correlated with brain T2 LV, but moderately correlated with DT MRI‐measured damage of the left CST. In conclusion, large multicenter fMRI studies of effective connectivity changes in diseased people are feasible and can facilitate studies with sample size large enough for robust outcomes. Increased effective connectivity in the patients for the simple motor task suggests local network modulation contributing to enhanced long‐distance effective connectivity in MS patients. This extends and generalizes previous evidence that enhancement of effective connectivity may provide an important compensatory mechanism in MS. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.     

Precentral degeneration and cerebellar compensation in amyotrophic lateral sclerosis: A multimodal MRI analysis

Amyotrophic lateral sclerosis (ALS) is a progressive and intractable neurodegenerative disease of human motor system characterized by progressive muscular weakness and atrophy. A considerable body of research has demonstrated significant structural and functional abnormalities of the primary motor cortex in patients with ALS. In contrast, much less attention has been paid to the abnormalities of cerebellum in this disease. Using multimodal magnetic resonance imagining data of 60 patients with ALS and 60 healthy controls, we examined changes in gray matter volume (GMV), white matter (WM) fractional anisotropy (FA), and functional connectivity (FC) in patients with ALS. Compared with healthy controls, patients with ALS showed decreased GMV in the left precentral gyrus and increased GMV in bilateral cerebellum, decreased FA in the left corticospinal tract and body of corpus callosum, and decreased FC in multiple brain regions, involving bilateral postcentral gyrus, precentral gyrus and cerebellum anterior lobe, among others. Meanwhile, we found significant intermodal correlations among GMV of left precentral gyrus, FA of altered WM tracts, and FC of left precentral gyrus, and that WM microstructural alterations seem to play important roles in mediating the relationship between GMV and FC of the precentral gyrus, as well as the relationship between GMVs of the precentral gyrus and cerebellum. These findings provided evidence for the precentral degeneration and cerebellar compensation in ALS, and the involvement of WM alterations in mediating the relationship between pathologies of the primary motor cortex and cerebellum, which may contribute to a better understanding of the pathophysiology of ALS.     

Disrupted thalamocortical connectivity in PSP: a resting-state fMRI, DTI, and VBM study

Progressive supranuclear palsy (PSP) is associated with pathological changes along the dentatorubrothalamic tract and in premotor cortex. We aimed to assess whether functional neural connectivity is disrupted along this pathway in PSP, and to determine how functional changes relate to changes in structure and diffusion. Eighteen probable PSP subjects and 18 controls had resting-state (task-free) fMRI, diffusion tensor imaging and structural MRI. Functional connectivity was assessed between thalamus and the rest of the brain, and within the basal ganglia, salience and default mode networks (DMN). Patterns of atrophy were assessed using voxel-based morphometry, and patterns of white matter tract degeneration were assessed using tract-based spatial statistics. Reduced in-phase functional connectivity was observed between the thalamus and premotor cortex including supplemental motor area (SMA), striatum, thalamus and cerebellum in PSP. Reduced connectivity in premotor cortex, striatum and thalamus were observed in the basal ganglia network and DMN, with subcortical salience network reductions. Tract degeneration was observed between cerebellum and thalamus and in superior longitudinal fasciculus, with grey matter loss in frontal lobe, premotor cortex, SMA and caudate nucleus. SMA functional connectivity correlated with SMA volume and measures of cognitive and motor dysfunction, while thalamic connectivity correlated with degeneration of superior cerebellar peduncles. PSP is therefore associated with disrupted thalamocortical connectivity that is associated with degeneration of the dentatorubrothalamic tract and the presence of cortical atrophy.     

Functional Connectivity Differences of the Subthalamic Nucleus Related to Parkinson's Disease

A typical feature of Parkinson's disease (PD) is pathological activity in the subthalamic nucleus (STN). Here, we tested whether in patients with PD under dopaminergic treatment functional connectivity of the STN differs from healthy controls (HC) and whether some brain regions show (anti‐) correlations between functional connectivity with STN and motor symptoms. We used functional magnetic resonance imaging to investigate whole‐brain resting‐state functional connectivity with STN in 54 patients with PD and 55 HC matched for age, gender, and within‐scanner motion. Compared to HC, we found attenuated negative STN‐coupling with Crus I of the right cerebellum and with right ventromedial prefrontal regions in patients with PD. Furthermore, we observed enhanced negative STN‐coupling with bilateral intraparietal sulcus/superior parietal cortex, right sensorimotor, right premotor, and left visual cortex compared to HC. Finally, we found a decline in positive STN‐coupling with the left insula related to severity of motor symptoms and a decline of inter‐hemispheric functional connectivity between left and right STN with progression of PD‐related motor symptoms. Motor symptom related uncoupling of the insula, a key region in the saliency network and for executive function, from the STN might be associated with well‐known executive dysfunction in PD. Moreover, uncoupling between insula and STN might also induce an insufficient setting of thresholds for the discrimination between relevant and irrelevant salient environmental stimuli, explaining observations of disturbed response control in PD. In sum, motor symptoms in PD are associated with a reduced coupling between STN and a key region for executive function. Hum Brain Mapp 37:1235–1253, 2016. © 2015 Wiley Periodicals, Inc .     

Structural and functional magnetic resonance imaging correlates of motor network dysfunction in primary progressive multiple sclerosis

We combined functional magnetic resonance imaging (fMRI) and diffusion tensor tractography to investigate the functional and structural substrates of motor network dysfunction in patients with primary progressive multiple sclerosis (PPMS). In 15 right‐handed PPMS patients and 15 age‐matched healthy controls, we acquired diffusion tensor magnetic resonance imaging and fMRI during the performance of a simple motor task. Tractography was used to calculate diffusion tensor‐derived measures of the corpus callosum, the corticospinal tract, the optic radiation, the fronto‐occipital fasciculus, and the inferior longitudinal fasciculus. Analyses of fMRI activations and functional connectivity were performed using statistical parametric mapping (cluster threshold of P = 0.001, and extent cluster threshold of 10 voxels for comparison of activations; P < 0.05, family‐wise error corrected for functional connectivity). As compared with controls, PPMS patients had more significant activations of the left postcentral gyrus, left secondary sensorimotor area, left parahippocampal gyrus, left cerebellum, right primary sensorimotor cortex (SMC), right basal ganglia, right insula, right cingulum, and cuneus bilaterally. As compared with PPMS patients, controls had increased functional connectivity between the left primary SMC and the ipsilateral inferior frontal gyrus. Conversely, PPMS patients showed increased functional connectivity between the left primary SMC and the right cuneus. Moderate correlations were found between functional activations and damage to the tracts studied (r‐values between 0.82 and 0.84; P < 0.001). These results suggest that, as compared with healthy controls, PPMS patients show increased activations and abnormal functional connectivity measures in several areas of the sensorimotor network. Such changes are correlated with the structural damage to the white matter fiber bundles connecting these regions.     

Subcortical motor plasticity in patients with sporadic ALS: An fMRI study

OBJECTIVE: To address the potential contribution of subcortical brain regions in the functional reorganization of the motor system in patients with sporadic ALS (sALS) and to investigate whether functional changes in brain activity are different in sALS patients with predominant upper motor neuron (UMN) or lower motor neuron (LMN) dysfunction. METHODS: We studied 16 patients with sALS and 13 healthy controls, using BOLD-fMRI, while they performed a simple visually paced motor task. Seven patients had definite clinical UMN signs while nine patients had prevalent clinical and electrophysiological LMN involvement. fMRI data were analyzed with Brain Voyager QX. RESULTS: Task-related functional changes were identified in motor cortical regions in both patients and healthy controls. Direct group comparisons revealed relatively decreased BOLD fMRI responses in left sensorimotor cortex, lateral premotor area, supplementary motor area and right posterior parietal cortex (p < 0.05 corrected) and relatively increased responses in the left anterior putamen (p < 0.001 uncorrected) in sALS patients. Additional analyses between the two patients subgroups demonstrated significant BOLD fMRI response differences in the anterior cingulate cortex and right caudate nucleus (p < 0.001 uncorrected) with more robust activation of these areas in patients with greater UMN burden. Importantly, there were no significant differences in performance of the motor task between sALS patients and controls as well as between sALS patient subgroups. CONCLUSIONS: Our data demonstrate a different BOLD fMRI pattern between our sALS patients and healthy controls even during simple motor behavior. Furthermore, patients with sALS and greater UMN involvement show a different reorganization of the motor system compared to sALS patients with greater LMN dysfunction.     

Disruption of visual and motor connectivity in spinocerebellar ataxia type 7

Spinocerebellar ataxia type 7 (SCA7) is an autosomal‐dominant neurodegenerative disorder characterized by progressive ataxia and retinal dystrophy. It is caused by a CAG trinucleotide expansion in the ataxin7 gene. Anatomical studies have shown severe cerebellar degeneration and region‐specific neocortical atrophy in SCA7 patients. However, the impact of the neurodegeneration on the functional integration of the remaining tissue is still unknown. The aim of this study was to examine functional connectivity abnormalities in areas with significant gray matter atrophy in SCA7 patients and their relationship with number of CAG repeats. Using a combination of voxel‐based morphometry and resting‐state fMRI, we studied 26 genetically confirmed SCA7 patients and aged‐matched healthy controls. In SCA7 patients we found reduced functional interaction between the cerebellum and the middle and superior frontal gyri, disrupted functional connectivity between the visual and motor cortices, and increased functional coordination between atrophied areas of the cerebellum and a range of visual cortical areas compared with healthy controls. The degree of mutation expansion showed a negative effect on both the functional interaction between the right anterior cerebellum and the left superior frontal gyrus and the connectivity between the right anterior cerebellum and left parahippocampal gyrus. We found abnormal functional connectivity patterns, including both hypo‐ and hyperconnectivity, compared with controls. These abnormal patterns show reasonable association with the severity of gene mutation. Our findings suggest that aberrant changes are prevalent in both motor and visual systems, adding significantly to our understanding of the pathophysiology of SCA7. © 2013 International Parkinson and Movement Disorder Society     

Changes in brain activation patterns according to cross-training effect in serial reaction time task An functional MRI study

Cross-training is a phenomenon related to motor learning, where motor performance of the untrained limb shows improvement in strength and skill execution following unilateral training of the homologous contralateral limb. We used functional MRI to investigate whether motor performance of the untrained limb could be improved using a serial reaction time task according to motor sequential learning of the trained limb, and whether these skill acquisitions led to changes in brain activation patterns. We recruited 20 right-handed healthy subjects, who were randomly allocated into training and control groups. The training group was trained in performance of a serial reaction time task using their non-dominant left hand, 40 minutes per day, for 10 days, over a period of 2 weeks. The control group did not receive training. Measurements of response time and percentile of response accuracy were performed twice during pre- and post-training, while brain functional MRI was scanned during performance of the serial reaction time task using the untrained right hand. In the training group, prominent changes in response time and percentile of response accuracy were observed in both the untrained right hand and the trained left hand between pre- and post-training. The control group showed no significant changes in the untrained hand between pre- and post-training. In the training group, the activated volume of the cortical areas related to motor function (i.e., primary motor cortex, premotor area, posterior parietal cortex) showed a gradual decrease, and enhanced cerebellar activation of the vermis and the newly activated ipsilateral dentate nucleus were observed during performance of the serial reaction time task using the untrained right hand, accompanied by the cross-motor learning effect. However, no significant changes were observed in the control group. Our findings indicate that motor skills learned over the 2-week training using the trained limb were transferred to the opposite homologous limb, and motor skill acquisition of the untrained limb led to changes in brain activation patterns in the cerebral cortex and cerebellum.     

Regional brain activation changes and abnormal functional connectivity of the ventrolateral prefrontal cortex during working memory processing in adults with attention‐deficit/hyperactivity disorder

Previous studies on working memory (WM) function in adults with attention‐deficit/hyperactivity disorder (ADHD) suggested aberrant activation of the prefrontal cortex and the cerebellum. Although it has been hypothesized that activation differences in these regions most likely reflect aberrant frontocerebellar circuits, the functional coupling of these brain networks during cognitive performance has not been investigated so far. In this study, functional magnetic resonance imaging (fMRI) and both univariate and multivariate analytic techniques were used to investigate regional activation changes and functional connectivity differences during cognitive processing in healthy controls (n = 12) and ADHD adults (n = 12). Behavioral performance during a parametric verbal WM paradigm did not significantly differ between adults with ADHD and healthy controls. During the delay period of the activation task, however, ADHD patients showed significantly less activation in the left ventrolateral prefrontal cortex (VLPFC), as well as in cerebellar and occipital regions compared with healthy control subjects. In both groups, independent component analyses revealed a functional network comprising bilateral lateral prefrontal, striatal, and cingulate regions. ADHD adults had significantly lower connectivity in the bilateral VLPFC, the anterior cingulate cortex, the superior parietal lobule, and the cerebellum compared with healthy controls. Increased connectivity in ADHD adults was found in right prefrontal regions, the left dorsal cingulate cortex and the left cuneus. These findings suggest both regional brain activation deficits and functional connectivity changes of the VLPFC and the cerebellum as well as functional connectivity abnormalities of the anterior cingulate and the parietal cortex in ADHD adults during WM processing. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.     

Remote effects of hippocampal damage on default network connectivity in the human brain

In the healthy human brain the hippocampus is known to work in concert with a variety of cortical brain regions. It has recently been linked to the default network of the brain, with the precuneus being its core hub. Here we studied the remote effects of damage to the hippocampus on functional connectivity patterns of the precuneus. From 14 epilepsy patients with selective, unilateral hippocampal sclerosis and 8 healthy control subjects, we acquired functional MRI data during performance of an object-location memory task. We assessed functional connectivity of a functionally defined region in the precuneus, which showed the typical properties of the default network: significant task-related deactivation, which was reduced in patients compared to control subjects. In control subjects, a largely symmetrical pattern of functional coherence to the precuneus emerged, including canonical default network areas such as ventral medial prefrontal cortex, inferior parietal cortex, and the hippocampi. Assessment of group differences within the default network areas revealed reduced connectivity to the precuneus in ipsilesional middle temporal gyrus and hippocampus in left hippocampal sclerosis patients compared to controls. Furthermore, left hippocampal sclerosis patients showed lower connectivity than right hippocampal sclerosis patients in left middle temporal gyrus, ventral medial prefrontal cortex, and left amygdala. We report remote effects of unilateral hippocampal damage on functional connectivity between distant brain regions associated with the default network of the human brain. These preliminary results underline the impact of circumscribed pathology on functionally connected brain regions.     

Lateralization of brain activity pattern during unilateral movement in Parkinson's disease

We investigated the lateralization of brain activity pattern during performance of unilateral movement in drug‐naïve Parkinson's disease (PD) patients with only right hemiparkinsonian symptoms. Functional MRI was obtained when the subjects performed strictly unilateral right hand movement. A laterality index was calculated to examine the lateralization. Patients had decreased activity in the left putamen and left supplementary motor area, but had increased activity in the right primary motor cortex, right premotor cortex, left postcentral gyrus, and bilateral cerebellum. The laterality index was significantly decreased in PD patients compared with controls (0.41 ± 0.14 vs. 0.84 ± 0.09). The connectivity from the left putamen to cortical motor regions and cerebellum was decreased, while the interactions between the cortical motor regions, cerebellum, and right putamen were increased. Our study demonstrates that in early PD, the lateralization of brain activity during unilateral movement is significantly reduced. The dysfunction of the striatum–cortical circuit, decreased transcallosal inhibition, and compensatory efforts from cortical motor regions, cerebellum, and the less affected striatum are likely reasons contributing to the reduced motor lateralization. The disruption of the lateralized brain activity pattern might be a reason underlying some motor deficits in PD, like mirror movements or impaired bilateral motor coordination. Hum Brain Mapp 36:1878–1891, 2015. © 2015 Wiley Periodicals, Inc .     

Resting-State Functional Connectivity Changes Between Dentate Nucleus and Cortical Social Brain Regions in Autism Spectrum Disorders

Autism spectrum disorders (ASDs) are known to be characterized by restricted and repetitive behaviors and interests and by impairments in social communication and interactions mainly including “theory of mind” (ToM) processes. The cerebellum has emerged as one of the brain regions affected by ASDs. As the cerebellum is known to influence cerebral cortex activity via cerebello-thalamo-cortical (CTC) circuits, it has been proposed that cerebello-cortical “disconnection” could in part underlie autistic symptoms. We used resting-state (RS) functional magnetic resonance imaging (fMRI) to investigate the potential RS connectivity changes between the cerebellar dentate nucleus (DN) and the CTC circuit targets, that may contribute to ASD pathophysiology. When comparing ASD patients to controls, we found decreased connectivity between the left DN and cerebral regions known to be components of the ToM network and the default mode network, implicated in specific aspects of mentalizing, social cognition processing, and higher order emotional processes. Further, a pattern of overconnectivity was also detected between the left DN and the supramodal cerebellar lobules associated with the default mode network. The presented RS-fMRI data provide evidence that functional connectivity (FC) between the dentate nucleus and the cerebral cortex is altered in ASD patients. This suggests that the dysfunction reported within the cerebral cortical network, typically related to social features of ASDs, may be at least partially related to an impaired interaction between cerebellum and key cortical social brain regions.     

Adaptive cortical changes and the functional correlates of visuo-motor integration in relapsing-remitting multiple sclerosis

Cortical reorganization has been demonstrated during performance of a motor task in patients with multiple sclerosis. Converging evidence suggests that changes in gray matter volume represent an early hallmark of the disease. We used functional MRI to investigate the role of cortical adaptive mechanisms in maintaining visuo-motor function in the face of structural damage. Two cohorts of patients with clinically definite relapsing-remitting multiple sclerosis were compared with healthy controls matched for demographic, motor and cognitive characteristics during the performance of a visuo-motor integration task. Direct comparison between the two groups demonstrated a greater response of the contralateral dorsal premotor cortex and of the ipsilateral superior parietal cortex in relapsing-remitting multiple sclerosis patients. The functional MRI changes in these areas were strongly correlated with decreased gray matter volumes and increased lesion burden, respectively. Our study demonstrated a selective involvement of the parieto-premotor circuitry in a relatively early stage of the disease, which was not influenced by clinical, motor or cognitive variables. Moreover these results confirm the potential for functional recovery and the adaptive role of these areas in the motor reorganization of multiple sclerosis patients.     

Altered brain function in persistent postural perceptual dizziness: A study on resting state functional connectivity

This study used resting state functional magnetic resonance imaging (rsfMRI) to investigate whole brain networks in patients with persistent postural perceptual dizziness (PPPD). We compared rsfMRI data from 38 patients with PPPD and 38 healthy controls using whole brain and region of interest analyses. We examined correlations among connectivity and clinical variables and tested the ability of a machine learning algorithm to classify subjects using rsfMRI results. Patients with PPPD showed: (a) increased connectivity of subcallosal cortex with left superior lateral occipital cortex and left middle frontal gyrus, (b) decreased connectivity of left hippocampus with bilateral central opercular cortices, left posterior opercular cortex, right insular cortex and cerebellum, and (c) decreased connectivity between right nucleus accumbens and anterior left temporal fusiform cortex. After controlling for anxiety and depression as covariates, patients with PPPD still showed decreased connectivity between left hippocampus and right inferior frontal gyrus, bilateral temporal lobes, bilateral insular cortices, bilateral central opercular cortex, left parietal opercular cortex, bilateral occipital lobes and cerebellum (bilateral lobules VI and V, and left I–IV). Dizziness handicap, anxiety, and depression correlated with connectivity in clinically meaningful brain regions. The machine learning algorithm correctly classified patients and controls with a sensitivity of 78.4%, specificity of 76.9%, and area under the curve = 0.88 using 11 connectivity parameters. Patients with PPPD showed reduced connectivity among the areas involved in multisensory vestibular processing and spatial cognition, but increased connectivity in networks linking visual and emotional processing. Connectivity patterns may become an imaging biomarker of PPPD.     

Motor recovery at 6 months after admission is related to structural and functional reorganization of the spine and brain in patients with spinal cord injury

This study aimed to explore structural and functional reorganization of the brain in the early stages of spinal cord injury (SCI) and identify brain areas that contribute to motor recovery. We studied 25 patients with SCI, including 10 with good motor recovery and 15 with poor motor recovery, along with 25 matched healthy controls. The mean period post‐SCI was 9.2 ± 3.5 weeks in good recoverers and 8.8 ± 2.6 weeks in poor recoverers. All participants underwent structural and functional MRI on a 3‐T magnetic resonance system. We evaluated differences in cross‐sectional spinal cord area at the C2/C3 level, brain cortical thickness, white matter microstructure, and functional connectivity during the resting state among the three groups. We also evaluated associations between structural and functional reorganization and the rate of motor recovery. After SCI, compared with good recoverers, poor recoverers had a significantly decreased cross‐sectional spinal cord area, cortical thickness in the right supplementary motor area and premotor cortex, and fractional anisotropy (FA) in the right primary motor cortex and posterior limb of the internal capsule. Meanwhile, poor recoverers showed decreased functional connectivity between the primary motor cortex and higher order motor areas (supplementary motor area and premotor cortex), while good recoverers showed increased functional connectivity among these regions. The structural and functional reorganization of the spine and brain was associated with motor recovery rate in all SCI patients. In conclusion, structural and functional reorganization of the spine and brain directly affected the motor recovery of SCI. Less structural atrophy and enhanced functional connectivity are associated with good motor recovery in patients with SCI. Multimodal imaging has the potential to predict motor recovery in the early stage of SCI. Hum Brain Mapp 37:2195–2209, 2016. © 2016 Wiley Periodicals, Inc.     

Metabolic Changes of Cerebrum by Repetitive Transcranial Magnetic Stimulation over Lateral Cerebellum: A Study with FDG PET

To better understand the functional role of cerebellum within the large-scale cerebellocerebral neural network, we investigated the changes of neuronal activity elicited by cerebellar repetitive transcranial magnetic stimulation (rTMS) using (18)F-fluorodeoxyglucose (FDG) and positron emission tomography (PET). Twelve right-handed healthy volunteers were studied with brain FDG PET under two conditions: active rTMS of 1?Hz frequency over the left lateral cerebellum and sham stimulation. Compared to the sham condition, active rTMS induced decreased glucose metabolism in the stimulated left lateral cerebellum, the areas known to be involved in voluntary motor movement (supplementary motor area and posterior parietal cortex) in the right cerebral hemisphere, and the areas known to be involved in cognition and emotion (orbitofrontal, medial frontal, and anterior cingulate gyri) in the left cerebral hemisphere. Increased metabolism was found in cognition- and language-related brain regions such as the left inferior frontal gyrus including Broca's area, bilateral superior temporal gyri including Wernicke's area, and bilateral middle temporal gyri. Left cerebellar rTMS also led to increased metabolism in the left cerebellar dentate nucleus and pons. These results demonstrate that rTMS over the left lateral cerebellum modulates not only the target region excitability but also excitability of remote, but interconnected, motor-, language-, cognition-, and emotion-related cerebral regions. They provide further evidence that the cerebellum is involved not only in motor-related functions but also in higher cognitive abilities and emotion through the large-scale cerebellocereberal neural network.     

The brain network reflecting bodily self-consciousness: a functional connectivity study

Several brain regions are important for processing self-location and first-person perspective, two important aspects of bodily self-consciousness. However, the interplay between these regions has not been clarified. In addition, while self-location and first-person perspective in healthy subjects are associated with bilateral activity in temporoparietal junction (TPJ), disturbed self-location and first-person perspective result from damage of only the right TPJ. Identifying the involved brain network and understanding the role of hemispheric specializations in encoding self-location and first-person perspective, will provide important information on system-level interactions neurally mediating bodily self-consciousness. Here, we used functional connectivity and showed that right and left TPJ are bilaterally connected to supplementary motor area, ventral premotor cortex, insula, intraparietal sulcus and occipitotemporal cortex. Furthermore, the functional connectivity between right TPJ and right insula had the highest selectivity for changes in self-location and first-person perspective. Finally, functional connectivity revealed hemispheric differences showing that self-location and first-person perspective modulated the connectivity between right TPJ, right posterior insula, and right supplementary motor area, and between left TPJ and right anterior insula. The present data extend previous evidence on healthy populations and clinical observations in neurological deficits, supporting a bilateral, but right-hemispheric dominant, network for bodily self-consciousness.     

Altered regional homogeneity and connectivity in cerebellum and visual-motor relevant cortex in Parkinson's disease with rapid eye movement sleep behavior disorder

ObjectiveRapid eye movement sleep behavior disorder (RBD) frequently occurs in Parkinson's disease (PD), however, the exact pathophysiological mechanism underlying its occurrence is not clear. In this study, we explored whether there is abnormal spontaneous neuronal activities and connectivity maps in some brain areas under resting-state in PD patients with RBD.MethodsWe recruited 38 PD patients (19 PD with RBD and 19 PD without RBD), and 20 age- and gender-matched normal controls. We used resting-state functional magnetic resonance imaging (RS-fMRI) to analyze regional homogeneity (ReHo) and functional connectivity (FC), and further to reveal the neuronal activity in all subjects.ResultsCompared with the PD without RBD patients, the PD with RBD patients showed a significant increase in regional homogeneity in the left cerebellum, the right middle occipital region and the left middle temporal region, and decreased regional homogeneity in the left middle frontal region. The REM sleep behavioral disorders questionnaire scores were significantly positively correlated with the ReHo values of the left cerebellum. The functional connectivity analysis in which the four regions described above were used as regions of interest revealed increased functional activity between the left cerebellum and bilateral occipital regions, bilateral temporal regions and bilateral supplementary motor area.ConclusionThe pathophysiological mechanism of PD with RBD may be related to abnormal spontaneous neuronal activity patterns with strong synchronization of cerebellar and visual-motor relevant cortex, and the increased connectivity of the cerebellum with the occipital and motor regions.