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This study aims to investigate the structural reorganization in the sensorimotor area of the brain in patients with gliomas, distinguishing between those with impaired and unimpaired strength. Using voxel-based morphometry (VBM) and region of interest (ROI) analysis, gray matter volumes (GMV) were compared in the contralesional primary motor gyrus, primary sensory gyrus, premotor area, bilateral supplementary motor area, and medial Brodmann area 8 (BA8). The results revealed that in patients with right hemisphere gliomas, the right medial BA8 volume was significantly larger in the impaired group than in the unimpaired group, with both groups exceeding the volume in 16 healthy controls (HCs). In patients with left hemisphere gliomas, the right supplementary motor area (SMA) was more pronounced in the impaired group compared to the unimpaired group, and both groups were greater than HCs. Additionally, the volumes of the right medial BA8 in both the impaired group were greater than HCs. Contralateral expansions in the gray matter of hand- and trunk-related cortices of the premotor area, precentral gyrus, and postcentral gyrus were observed compared to HCs. Furthermore, a negative correlation was found between hand Medical Research Council (MRC) score and volumes of the contralateral SMA and bilateral medial BA8. Notably, our findings reveal consistent results across both analytical approaches in identifying significant structural reorganizations within the sensorimotor cortex. These consistent findings underscore the adaptive neuroplastic responses to glioma presence, highlighting potential areas of interest for further neurosurgical planning and rehabilitation strategies., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Aims: To explore the novel linkage between a Western diet combining high saturated fat, sugar, and salt (HFSS) and neurological dysfunctions during aging as well as Metformin intervention, we assessed cerebral cortex abnormalities associated with sensory and motor dysfunctions and cellular and molecular insights in brains using HFSS-fed mice during aging. We also explored the effect of Metformin treatment on these mice., Methods: C57BL/6 mice were fed with HFSS and treated with metformin from 20 to 22 months of age, resembling human aging from 56 to 68 years of age (an entry phase of the aged portion of lifespan)., Results: The motor and sensory cortexes in mice during aging after HFSS diet showed: (A) decreased motor-muscular and sensory functions; (B) reduced inflammation-resolving Arg-1 + microglia; (C) increased inflammatory iNOs + microglia and TNFα levels; (D) enhanced abundance of amyloid-β peptide and of phosphorylated Tau. Metformin attenuated these changes., Conclusion: A HFSS-combined diet caused motor-muscular and sensory dysfunctions, neuroinflammation, and neurodegeneration, whereas metformin counteracted these effects. Our findings show neuroinflammatory consequences of a HFSS diet in aging. Metformin curbs the HFSS-related neuroinflammation eliciting neuroprotection., (© 2021 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background. Recovery of motor function after stroke appears to be related to the integrity of axonal connections in the corticospinal tract (CST) and corpus callosum, which may both be affected after cortical stroke. Objective. In the present study, we aimed to elucidate the relationship of changes in measures of the CST and transcallosal tract integrity, with the interhemispheric functional connectivity and sensorimotor performance after experimental cortical stroke. Methods. We conducted in vivo diffusion magnetic resonance imaging (MRI), resting-state functional MRI, and behavior testing in twenty-five male Sprague Dawley rats recovering from unilateral photothrombotic stroke in the sensorimotor cortex. Twenty-three healthy rats served as controls. Results. A reduction in the number of reconstructed fibers, a lower fractional anisotropy, and higher radial diffusivity in the ipsilesional but intact CST, reflected remote white matter degeneration. In contrast, transcallosal tract integrity remained preserved. Functional connectivity between the ipsi- and contralesional forelimb regions of the primary somatosensory cortex significantly reduced at week 8 post-stroke. Comparably, usage of the stroke-affected forelimb was normal at week 28, following significant initial impairment between day 1 and week 8 post-stroke. Conclusions. Our study shows that post-stroke motor recovery is possible despite degeneration in the CST and may be supported by intact neuronal communication between hemispheres.

Infants born very preterm (VPT) are at high risk of motor impairments such as cerebral palsy (CP), and diagnosis can take 2 years. Identifying in vivo determinants of CP could facilitate presymptomatic detection and targeted intervention. Our objectives were to derive micro- and macrostructural measures of sensorimotor white matter tract integrity from diffusion MRI at term-equivalent age, and determine their association with early diagnosis of CP. We enrolled 263 VPT infants (≤32 weeks gestational age) as part of a large prospective cohort study. Diffusion and structural MRI were acquired at term. Following consensus guidelines, we defined early diagnosis of CP based on abnormal structural MRI at term and abnormal neuromotor exam at 3-4 months corrected age. Using Constrained Spherical Deconvolution, we derived a white matter fiber orientation distribution (fOD) for subjects, performed probabilistic whole-brain tractography, and segmented nine sensorimotor tracts of interest. We used the recently developed fixel-based (FB) analysis to compute fiber density (FD), fiber-bundle cross-section (FC), and combined fiber density and cross-section (FDC) for each tract. Of 223 VPT infants with high-quality diffusion MRI data, 14 (6.3%) received an early diagnosis of CP. The cohort's mean (SD) gestational age was 29.4 (2.4) weeks and postmenstrual age at MRI scan was 42.8 (1.3) weeks. FD, FC, and FDC for each sensorimotor tract were significantly associated with early CP diagnosis, with and without adjustment for confounders. Measures of sensorimotor tract integrity enhance our understanding of white matter changes that antecede and potentially contribute to the development of CP in VPT infants., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Acute ischemic stroke affects men and women differently. In particular, women are often reported to experience higher acute stroke severity than men. We derived a low-dimensional representation of anatomical stroke lesions and designed a Bayesian hierarchical modeling framework tailored to estimate possible sex differences in lesion patterns linked to acute stroke severity (National Institute of Health Stroke Scale). This framework was developed in 555 patients (38% female). Findings were validated in an independent cohort (n = 503, 41% female). Here, we show brain lesions in regions subserving motor and language functions help explain stroke severity in both men and women, however more widespread lesion patterns are relevant in female patients. Higher stroke severity in women, but not men, is associated with left hemisphere lesions in the vicinity of the posterior circulation. Our results suggest there are sex-specific functional cerebral asymmetries that may be important for future investigations of sex-stratified approaches to management of acute ischemic stroke.

To validate a simultaneous analysis tool for the brain and cervical cord embedded in the statistical parametric mapping (SPM) framework, we compared trauma-induced macro- and microstructural changes in spinal cord injury (SCI) patients to controls. The findings were compared with results obtained from existing processing tools that assess the brain and spinal cord separately. A probabilistic brain-spinal cord template (BSC) was generated using a generative semi-supervised modelling approach. The template was incorporated into the pre-processing pipeline of voxel-based morphometry and voxel-based quantification analyses in SPM. This approach was validated on T1-weighted scans and multiparameter maps, by assessing trauma-induced changes in SCI patients relative to controls and comparing the findings with the outcome from existing analytical tools. Consistency of the MRI measures was assessed using intraclass correlation coefficients (ICC). The SPM approach using the BSC template revealed trauma-induced changes across the sensorimotor system in the cord and brain in SCI patients. These changes were confirmed with established approaches covering brain or cord, separately. The ICC in the brain was high within regions of interest, such as the sensorimotor cortices, corticospinal tracts and thalamus. The simultaneous voxel-wise analysis of brain and cervical spinal cord was performed in a unique SPM-based framework incorporating pre-processing and statistical analysis in the same environment. Validation based on a SCI cohort demonstrated that the new processing approach based on the brain and cord is comparable to available processing tools, while offering the advantage of performing the analysis simultaneously across the neuraxis., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Frequently reported neurotoxic sequelae of cancer treatment include cognitive deficits and sensorimotor abnormalities that have long-lasting negative effects on the quality of life of an increasing number of cancer survivors. The underlying mechanisms are not fully understood and there is no effective treatment. We show here that cisplatin treatment of mice not only caused cognitive dysfunction but also impaired sensorimotor function. These functional deficits are associated with reduced myelin density and complexity in the cingulate and sensorimotor cortex. At the ultrastructural level, myelin abnormalities were characterized by decompaction. We used this model to examine the effect of bexarotene, an agonist of the RXR-family of nuclear receptors. Administration of only five daily doses of bexarotene after completion of cisplatin treatment was sufficient to normalize myelin density and fiber coherency and to restore myelin compaction in cingulate and sensorimotor cortex. Functionally, bexarotene normalized performance of cisplatin-treated mice in tests for cognitive and sensorimotor function. RNAseq analysis identified the TR/RXR pathway as one of the top canonical pathways activated by administration of bexarotene to cisplatin-treated mice. Bexarotene also activated neuregulin and netrin pathways that are implicated in myelin formation/maintenance, synaptic function and axonal guidance. In conclusion, short term treatment with bexarotene is sufficient to reverse the adverse effects of cisplatin on white matter structure, cognitive function, and sensorimotor performance. These encouraging findings warrant further studies into potential clinical translation and the underlying mechanisms of bexarotene for chemobrain.

Graph theory and network modelling have been previously applied to characterize motor network structural topology in multiple sclerosis (MS). However, between-group differences disclosed by graph analysis might be primarily driven by discrepancy in density, which is likely to be reduced in pathologic conditions as a consequence of macroscopic damage and fibre loss that may result in less streamlines properly traced. In this work, we employed the convex optimization modelling for microstructure informed tractography (COMMIT) framework, which, given a tractogram, estimates the actual contribution (or weight) of each streamline in order to optimally explain the diffusion magnetic resonance imaging signal, filtering out those that are implausible or not necessary. Then, we analysed the topology of this 'COMMIT-weighted sensory-motor network' in MS accounting for network density. By comparing with standard connectivity analysis, we also tested if abnormalities in network topology are still identifiable when focusing on more 'quantitative' network properties. We found that topology differences identified with standard tractography in MS seem to be mainly driven by density, which, in turn, is strongly influenced by the presence of lesions. We were able to identify a significant difference in density but also in network global and local properties when accounting for density discrepancy. Therefore, we believe that COMMIT may help characterize the structural organization in pathological conditions, allowing a fair comparison of connectomes which considers discrepancies in network density. Moreover, discrepancy-corrected network properties are clinically meaningful and may help guide prognosis assessment and treatment choice., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

The sense of agency (SoA) refers to the perception that an action is the consequence of one's own intention. Studies exploring the SoA with neuroimaging techniques summarized the available data and confirmed a role of fronto-parietal areas and subcortical structures. However, these studies focused on specific regions of interest. We thus conducted a whole-brain meta-analysis to verify which regions emerge as significant for the SoA, specifically during motor execution. We performed a systematic search on PubMed, PsycINFO and Cochrane databases with the following inclusion criteria: studies investigating SoA with a visuo-motor task by means of neuroimaging in healthy subjects. We performed a quantitative, whole-brain, meta-analysis of neural correlates of the SoA based on the activation likelihood estimation. Of the 785 articles identified by our search, 22 studies met our inclusion criteria (169 foci, 295 subjects for decreased agency, and 58 foci, 165 subjects for normal agency). Neural correlates of decreased agency were the bilateral temporo-parietal junction (MNI: 50,-54,14; -44,-52,42; -48,-56,8). Normal agency showed no significant clusters of activation. This meta-analysis confirmed the key role of areas responsible for decreased SoA during motor control, whereas normal agency did not show a specific neural signature. This study sets the ground for future regions-of-interest analyses of neural correlates of SoA, as well as potential neuromodulation studies, which might be relevant in medical conditions presenting with abnormal SoA., Competing Interests: The authors have declared that no competing interests exist.

Importance: Developmental coordination disorder (DCD) is a motor impairment that significantly interferes with activities of daily living. Little is known about the cause of DCD and how it develops, making it difficult to understand why children with DCD struggle in learning motor skills and to determine the best intervention to optimize function., Objective: To characterize white matter differences using diffusion tensor imaging in children with and without DCD., Design, Setting, and Participants: This cross-sectional study collected diffusion tensor imaging data at BC Children's Hospital Research Institute in Vancouver, British Columbia, Canada, from September 2014 to January 2017. Using a sample of convenience, children with DCD and children without DCD aged 8 to 12 years underwent magnetic resonance imaging. Data analysis was conducted from January 2017 to January 2020., Main Outcomes and Measures: The main outcome measures were diffusion parameters, including fractional anisotropy and mean, axial, and radial diffusivity, which are thought to provide an indirect measure of white matter microstructure. Tract-based spatial statistics, a voxelwise statistical analysis of diffusion parameters, were conducted using a 2-group comparison design matrix with age and attention as covariates., Results: Thirty children without DCD (mean [SD] age, 9.9 [1.4] years; 21 [70%] boys) and 31 children with DCD (mean [SD] age, 10.1 [1.2] years; 26 [84%] boys) were included in the study. Compared with children without DCD, children with DCD were characterized by significantly lower fractional anisotropy and axial diffusivity in regions of white matter pathways associated with motor and sensorimotor processing, including the corticospinal tract (fractional anisotropy: mean [SD], 0.54 [0.03] vs 0.51 [0.03]; P < .001; axial diffusivity: mean [SD], 0.13 [0.98] vs 0.12 [0.46]; P = .01), posterior thalamic radiation at the retrolenticular part of the internal capsule (axial diffusivity: mean [SD], 0.14 [0.57] vs 0.14 [0.44]; P = .01), and cerebellar pathways (eg, superior cerebellar peduncle, fractional anisotropy: mean [SD], 0.49 [0.05] vs 0.46 [0.03]; P = .03; axial diffusivity: mean [SD], 0.14 [0.66] vs 0.14 [0.63]; P = .009). There were no significant differences in mean diffusivity and radial diffusivity between children with and without DCD., Conclusions and Relevance: These findings suggest that children with DCD show significant brain differences in motor and sensorimotor white matter pathways compared with children without DCD. The pattern of diffusion parameters in children with DCD suggests that axonal development may be disrupted in this neurodevelopmental disorder.

There is ongoing debate regarding the role that sensorimotor regions play in conceptual processing, with embodied theories supporting their direct involvement in processing verbs describing body part movements. Patient lesion studies examining a causal role for sensorimotor activation in conceptual task performance have suffered the caveat of lesions being largely diffuse and extensive beyond sensorimotor cortices. The current study addresses this limitation in reporting on 20 pre-operative neurosurgical patients with focal lesion to the pre- and post-central area corresponding to somatotopic representations. Patients were presented with a battery of neuropsychological tests and experimental tasks tapping into motor imagery and verbal conceptual verb processing in addition to neurophysiological measures including DTI, fMRI, and MEP being measured. Results indicated that left tumor patients who presented with a lesion at or near somatotopic hand representations performed significantly worse on the mental rotation hand task and that performance correlated with MEP amplitudes in the upper limb motor region. Furthermore, performance on tasks of verbal processing was within the normal range. Taken together, while our results evidence the involvement of the motor system in motor imagery processes, they do not support the embodied view that sensorimotor regions are necessary to tasks of action verb processing.

Background: Vacuolar sorting protein 35 (VPS35), a critical component of retromer, is essential for selective endosome-to-Golgi retrieval of membrane proteins. It is highly expressed in microglial cells, in addition to neurons. We have previously demonstrated microglial VPS35's functions in preventing hippocampal, but not cortical, microglial activation, and in promoting adult hippocampal neurogenesis. However, microglial VPS35's role in the cortex in response to ischemic stroke remains largely unclear., Methods: We used mice with VPS35 cKO (conditional knockout) in microglial cells and examined and compared their responses to ischemic stroke with control mice. The brain damage, cell death, changes in glial cells and gene expression, and sensorimotor deficits were assessed by a combination of immunohistochemical and immunofluorescence staining, RT-PCR, Western blot, and neurological functional behavior tests., Results: We found that microglial VPS35 loss results in an increase of anti-inflammatory microglia in mouse cortex after ischemic stroke. The ischemic stroke-induced brain injury phenotypes, including brain damage, neuronal death, and sensorimotor deficits, were all attenuated by microglial VPS35-deficiency. Further analysis of protein expression changes revealed a reduction in CX3CR1 (CX3C chemokine receptor 1) in microglial VPS35-deficient cortex after ischemic stroke, implicating CX3CR1 as a potential cargo of VPS35 in this event., Conclusion: Together, these results reveal an unrecognized function of microglial VPS35 in enhancing ischemic brain injury-induced inflammatory microglia, but suppressing the injury-induced anti-inflammatory microglia. Consequently, microglial VPS35 cKO mice exhibit attenuation of ischemic brain injury response.

Caloric restriction (CR) has been extensively examined as a preventative strategy against aging and various diseases, but CR effects on cerebral ischemia are largely unknown. We subjected C57BL6/J mice to ad libitum food access (LF) or a diet restricted to 70% of ad libitum food access (RF) for two to four weeks followed by 60 min of transient focal ischemia (tFCI). RF for four weeks protected against subsequent tFCI-induced infarct. RF improved sensorimotor function after stroke in the foot fault and corner tests, as well as performance in the Morris water maze test. In addition, RF preserved ischemic white matter tract integrity assessed by histology and compound action potential. Sirt1 and Sirt3 were both upregulated in RF ischemic brain, but heterozygous deletion of Sirt1 or knockout of Sirt3 did not alter the protection induced by RF against ischemic injury. RF induced significant release of adiponectin, a hormone related to glucose metabolism. Knockout of adiponectin decreased RF-induced protection after tFCI. These data demonstrate the novel finding that white matter, as well as neurons, benefit from CR prior to cerebral ischemic injury, and that adiponectin may contribute to these protective effects.

The stroke model of distal middle cerebral artery occlusion is considered a reliable stroke model with high reproducibility and low mortality rate. Thus, it is preferred for assessments of therapeutic strategies, in particular for neurorepair and regeneration studies. However, present literature has reported only on the lesion behavior and behavioral deficits during the acute and subacute phase of maximally three weeks. We have here aimed to characterize the lesion expansion and consequent, potential tissue displacements using structural magnetic resonance imaging modalities, histology, and behavioral tests, during the chronic time window of 12 weeks following stroke induction. We found a severe cortical thinning resulting in 15% tissue loss of the ipsilateral cortex by 6 weeks. After two weeks, massive hippocampus displacement was found, into the cortical tissue void and, in this process, pushing the corpus callosum to the brain surface showing an almost radial direction towards the surface. These massive chronic morphological changes and rearrangements, not known from other stroke models, have relevant consequences for decision of stem cell graft placement for cerebral regeneration to assure persistent graft vitality during a longitudinal investigation in the chronic phase.

The tropomyosin-receptor kinase fused gene (TFG) has recently been implicated in several distinct hereditary disorders, including the autosomal-recessive form of complicated hereditary spastic paraplegia called SPG57. Previously, three homozygous variants of the TFG gene were reported in five families with SPG57, in which early onset spastic paraplegia, optic atrophy, and peripheral neuropathy were variably identified. Here, we present the first Japanese patient with SPG57, and have added a homozygous p.Ile66Thr variant as the fourth SPG57 genotype.

Many stroke survivors experience persisting episodic memory disturbances. Since hippocampal and para-hippocampal areas are usually spared from the infarcted area, alterations of memory processing networks remote from the ischemic brain region might be responsible for the observed clinical symptoms. To pinpoint changes in activity of hippocampal connections and their role in post-stroke cognitive impairment, we induced ischemic stroke by occlusion of the middle cerebral artery (MCAO) in adult rats and analyzed the functional and structural consequences using activity-dependent manganese (Mn 2+ ) enhanced MRI (MEMRI) along with behavioral and histopathological analysis. MCAO caused stroke lesions of variable extent along with sensorimotor and cognitive deficits. Direct hippocampal injury occurred in some rats, but was no prerequisite for cognitive impairment. In healthy rats, injection of Mn 2+ into the entorhinal cortex resulted in distribution of the tracer within the hippocampal subfields into the lateral septal nuclei. In MCAO rats, Mn 2+ accumulated in the ipsilateral thalamus. Histopathological analysis revealed secondary thalamic degeneration 28 days after stroke. Our findings provide in vivo evidence that remote sensorimotor stroke modifies the activity of hippocampal-thalamic networks. In addition to potentially reversible alterations in signaling of these connections, structural damage of the thalamus likely reinforces dysfunction of hippocampal-thalamic circuitries.

In the mature mammalian brain, the primary somatosensory and motor cortices are known to be spatially organized such that neural activity relating to specific body parts can be somatopically mapped onto an anatomical "homunculus". This organization creates an internal body representation which is fundamental for precise motor control, spatial awareness and social interaction. Although it is unknown when this organization develops in humans, animal studies suggest that it may emerge even before the time of normal birth. We therefore characterized the somatotopic organization of the primary sensorimotor cortices using functional MRI and a set of custom-made robotic tools in 35 healthy preterm infants aged from 31 + 6 to 36 + 3 weeks postmenstrual age. Functional responses induced by somatosensory stimulation of the wrists, ankles, and mouth had a distinct spatial organization as seen in the characteristic mature homunculus map. In comparison to the ankle, activation related to wrist stimulation was significantly larger and more commonly involved additional areas including the supplementary motor area and ipsilateral sensorimotor cortex. These results are in keeping with early intrinsic determination of a somatotopic map within the primary sensorimotor cortices. This may explain why acquired brain injury in this region during the preterm period cannot be compensated for by cortical reorganization and therefore can lead to long-lasting motor and sensory impairment.

Individuals with type-2 diabetes mellitus experience poor motor outcomes after ischemic stroke. Recent research suggests that type-2 diabetes adversely impacts neuronal integrity and function, yet little work has considered how these neuronal changes affect sensorimotor outcomes after stroke. Here, we considered how type-2 diabetes impacted the structural and metabolic function of the sensorimotor cortex after stroke using volumetric magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). We hypothesized that the combination of chronic stroke and type-2 diabetes would negatively impact the integrity of sensorimotor cortex as compared to individuals with chronic stroke alone. Compared to stroke alone, individuals with stroke and diabetes had lower cortical thickness bilaterally in the primary somatosensory cortex, and primary and secondary motor cortices. Individuals with stroke and diabetes also showed reduced creatine levels bilaterally in the sensorimotor cortex. Contralesional primary and secondary motor cortex thicknesses were negatively related to sensorimotor outcomes in the paretic upper-limb in the stroke and diabetes group such that those with thinner primary and secondary motor cortices had better motor function. These data suggest that type-2 diabetes alters cerebral energy metabolism, and is associated with thinning of sensorimotor cortex after stroke. These factors may influence motor outcomes after stroke.

Children with prenatal alcohol exposure (PAE) often have impaired sensorimotor function. While altered brain structure has been noted in sensorimotor areas, the functional brain alterations remain unclear. This study aims to investigate sensorimotor brain networks in children and youth with PAE using resting-state functional magnetic resonance imaging (rs-fMRI). A parcellation-based network analysis was performed to identify brain networks related to hand/lower limb and face/upper limb function in 59 children and youth with PAE and 50 typically developing controls. Participants with PAE and controls had similar organization of the hand and face areas within the primary sensorimotor cortex, but participants with PAE had altered functional connectivity (FC) between the sensorimotor regions and the rest of the brain. The sensorimotor regions in the PAE group showed less connectivity to certain hubs of the default mode network and more connectivity to areas of the salience network. Overall, our results show that despite similar patterns of organization in the sensorimotor network, subjects with PAE have increased FC between this network and other brain areas, perhaps suggesting overcompensation. These alterations in the sensorimotor network lay the foundation for future studies to evaluate interventions and treatments to improve motor function in children with PAE., (© 2018 Wiley Periodicals, Inc.)

In a rodent model of Parkinson's disease (PD), levodopa-induced involuntary movements have been linked to striatal angiogenesis - a process that is difficult to document in living human subjects. Angiogenesis can be accompanied by localized increases in cerebral blood flow (CBF) responses to hypercapnia. We therefore explored the possibility that, in the absence of levodopa, local hypercapnic CBF responses are abnormally increased in PD patients with levodopa-induced dyskinesias (LID) but not in their nondyskinetic (NLID) counterparts. We used H215O PET to scan 24 unmedicated PD subjects (12 LID and 12 NLID) and 12 matched healthy subjects in the rest state under normocapnic and hypercapnic conditions. Hypercapnic CBF responses were compared to corresponding levodopa responses from the same subjects. Group differences in hypercapnic vasoreactivity were significant only in the posterior putamen, with greater CBF responses in LID subjects compared with the other subjects. Hypercapnic and levodopa-mediated CBF responses measured in this region exhibited distinct associations with disease severity: the former correlated with off-state motor disability ratings but not symptom duration, whereas the latter correlated with symptom duration but not motor disability. These are the first in vivo human findings linking LID to microvascular changes in the basal ganglia.

MEIS1 encodes a developmental transcription factor and has been linked to restless legs syndrome (RLS) in genome-wide association studies. RLS is a movement disorder leading to severe sleep reduction and has a substantial impact on the quality of life of patients. In genome-wide association studies, MEIS1 has consistently been the gene with the highest effect size and functional studies suggest a disease-relevant downregulation. Therefore, haploinsufficiency of Meis1 could be the system with the most potential for modeling RLS in animals. We used heterozygous Meis1 -knockout mice to study the effects of Meis1 haploinsufficiency on mouse behavioral and neurological phenotypes, and to relate the findings to human RLS. We exposed the Meis1 -deficient mice to assays of motor, sensorimotor and cognitive ability, and assessed the effect of a dopaminergic receptor 2/3 agonist commonly used in the treatment of RLS. The mutant mice showed a pattern of circadian hyperactivity, which is compatible with human RLS. Moreover, we discovered a replicable prepulse inhibition (PPI) deficit in the Meis1 -deficient animals. In addition, these mice were hyposensitive to the PPI-reducing effect of the dopaminergic receptor agonist, highlighting a role of Meis1 in the dopaminergic system. Other reported phenotypes include enhanced social recognition at an older age that was not related to alterations in adult olfactory bulb neurogenesis previously shown to be implicated in this behavior. In conclusion, the Meis1 -deficient mice fulfill some of the hallmarks of an RLS animal model, and revealed the role of Meis1 in sensorimotor gating and in the dopaminergic systems modulating it., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2017. Published by The Company of Biologists Ltd.)

Sulforhodamine 101 (SR101) is a preferential astrocyte marker widely used in 2-photon microscopy experiments. Here we show, that topical loading of two commonly used SR101 concentrations, 100 μM and 250 μM when incubated for 10 min, can induce seizure-like local field potential (LFP) activity in both anaesthetized and awake mouse sensori-motor cortex. This cortical seizure-like activity develops in less than ten minutes following topical loading, and when applied longer, these neuronal discharges reliably evoke contra-lateral hindlimb muscle contractions. Short duration (<1 min) incubation of 100 μM and 250 μM SR101 or application of lower concentrations 25 μM and 50 μM of SR101, incubated for 30 and 20 min, respectively, did not induce abnormal LFP activity in sensori-motor cortex, but did label astrocytes, and may thus be considered more appropriate concentrations for in vivo astrocyte labeling. In addition to label astrocytes SR101 may, at 100 μM and 250 μM, induce abnormal neuronal activity and interfere with cortical circuit activity. SR101 concentration of 50 μM or lower did not induce abnormal neuronal activity. We advocate that, to label astrocytes with SR101, concentrations no higher than 50 μM should be used for in vivo experiments.

Motor cortical plasticity contributes to spontaneous recovery after incomplete spinal cord injury (SCI), but the pathways underlying this remain poorly understood. We performed optogenetic mapping of motor cortex in channelrhodopsin-2 expressing mice to assess the capacity of the cortex to re-establish motor output longitudinally after a C3/C4 dorsal column SCI that bilaterally ablated the dorsal corticospinal tract (CST) containing ∼96% of corticospinal fibers but spared ∼3% of CST fibers that project via the dorsolateral funiculus. Optogenetic mapping revealed extensive early deficits, but eventual reestablishment of motor cortical output maps to the limbs at the same latency as preoperatively by 4 weeks after injury. Analysis of skilled locomotion on the horizontal ladder revealed early deficits followed by partial spontaneous recovery by 6 weeks after injury. To dissociate between the contributions of injured dorsal projecting versus spared dorsolateral projecting corticospinal neurons, we established a transient silencing approach to inactivate spared dorsolaterally projecting corticospinal neurons specifically by injecting adeno-associated virus (AAV)-expressing Cre-dependent DREADD (designer receptor exclusively activated by designer drug) receptor hM4Di in sensorimotor cortex and AAV-expressing Cre in C7/C8 dorsolateral funiculus. Transient silencing uninjured dorsolaterally projecting corticospinal neurons via activation of the inhibitory DREADD receptor hM4Di abrogated spontaneous recovery and resulted in a greater change in skilled locomotion than in control uninjured mice using the same silencing approach. These data demonstrate the pivotal role of a minor dorsolateral corticospinal pathway in mediating spontaneous recovery after SCI and support a focus on spared corticospinal neurons as a target for therapy., Significance Statement: Spontaneous recovery can occur after incomplete spinal cord injury (SCI), but the pathways underlying this remain poorly understood. We performed optogenetic mapping of motor cortex after a cervical SCI that interrupts most corticospinal transmission but results in partial recovery on a horizontal ladder task of sensorimotor function. We demonstrate that the motor cortex can reestablish output to the limbs longitudinally. To dissociate the roles of injured and uninjured corticospinal neurons in mediating recovery, we transiently silenced the minor dorsolateral corticospinal pathway spared by our injury. This abrogated spontaneous recovery and resulted in a greater change in skilled locomotion than in uninjured mice using the same approach. Therefore, uninjured corticospinal neurons substantiate remarkable motor cortical plasticity and partial recovery after SCI., (Copyright © 2016 the authors 0270-6474/16/364081-13$15.00/0.)

Action observation therapy has been found to be effective in improving hand motor function in both adults with stroke and children with unilateral cerebral palsy. We here propose a provocative hypothesis arguing that the same therapy might be effective in very early intervention in infants with unilateral or asymmetric brain damage, but through a different underlying mechanism. If the activation of motor networks induced in infancy by action observation enhances the excitability of the damaged sensorimotor cortex, it could also accelerate the maturation of the corticospinal tract and the adaptive shaping of the spinal motor circuits. This hypothesis should be explored carefully in prospective studies and, if confirmed, might support the use of action observation therapy at a much earlier time than experimented so far., (© 2016 The Authors. Developmental Medicine & Child Neurology © 2016 Mac Keith Press.)

Motor and sensory deficits after spinal cord injury (SCI) result in functional reorganization of the sensorimotor network. While several task-evoked functional magnetic resonance imaging (fMRI) studies demonstrated functional alteration of the sensorimotor network in SCI, there has been no study of the possible alteration of resting-state functional connectivity using resting-state fMRI. The aim of this study was to investigate the changes of brain functional connectivity in the sensorimotor cortex of patients with SCI. We evaluated the functional connectivity scores between brain areas within the sensorimotor network in 18 patients with SCI and 18 controls. Our findings demonstrated that, compared with control subjects, patients with SCI showed increased functional connectivity between primary motor cortex and other motor areas, such as the supplementary motor area and basal ganglia. However, decreased functional connectivity between primary somatosensory cortex and secondary somatosensory cortex also was found in patients with SCI, compared with controls. These findings therefore demonstrated alteration of the resting-state sensorimotor network in patients with SCI, who showed increased connectivity between motor components, and decreased connectivity between sensory components, within the sensorimotor network, suggesting that motor components within the motor network increased in functional connectivity in order to compensate for motor deficits, whereas the sensory network did not show any such increases or compensation for sensory deficits.

Traumatic brain injury (TBI) is a leading cause of death worldwide. In recent studies, we have shown that experimental TBI caused an immediate (24-h post) suppression of neuronal processing, especially in supragranular cortical layers. We now examine the long-term effects of experimental TBI on the sensory cortex and how these changes may contribute to a range of TBI morbidities. Adult male Sprague-Dawley rats received either a moderate lateral fluid percussion injury (n=14) or a sham surgery (n=12) and 12 weeks of recovery before behavioral assessment, magnetic resonance imaging, and electrophysiological recordings from the barrel cortex. TBI rats demonstrated sensorimotor deficits, cognitive impairments, and anxiety-like behavior, and this was associated with significant atrophy of the barrel cortex and other brain structures. Extracellular recordings from ipsilateral barrel cortex revealed normal neuronal responsiveness and diffusion tensor MRI showed increased fractional anisotropy, axial diffusivity, and tract density within this region. These findings suggest that long-term recovery of neuronal responsiveness is owing to structural reorganization within this region. Therefore, it is likely that long-term structural and functional changes within sensory cortex post-TBI may allow for recovery of neuronal responsiveness, but that this recovery does not remediate all behavioral deficits.

The role of cortical activity in generating and abolishing chronic pain is increasingly emphasized in the clinical community. Perhaps the most striking example of this is the maladaptive plasticity theory, according to which phantom pain arises from remapping of cortically neighbouring representations (lower face) into the territory of the missing hand following amputation. This theory has been extended to a wide range of chronic pain conditions, such as complex regional pain syndrome. Yet, despite its growing popularity, the evidence to support the maladaptive plasticity theory is largely based on correlations between pain ratings and oftentimes crude measurements of cortical reorganization, with little consideration of potential contributions of other clinical factors, such as adaptive behaviour, in driving the identified brain plasticity. Here, we used a physiologically meaningful measurement of cortical reorganization to reassess its relationship to phantom pain in upper limb amputees. We identified small yet consistent shifts in lip representation contralateral to the missing hand towards, but not invading, the hand area. However, we were unable to identify any statistical relationship between cortical reorganization and phantom sensations or pain either with this measurement or with the traditional Euclidian distance measurement. Instead, we demonstrate that other factors may contribute to the observed remapping. Further research that reassesses more broadly the relationship between cortical reorganization and chronic pain is warranted., (© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Spinal cord injury (SCI) can induce remodeling of multiple levels of the cerebral cortex system especially in the sensory cortex. The aim of this study was to assess, in vivo and bilaterally, the remodeling of dendritic spines in the hindlimb representation of the sensory cortex after spinal cord hemisection. Thy1-YFP transgenic mice were randomly divided into the control group and the SCI group, and the spinal vertebral plates (T11-T12) of all mice were excised. Next, the left hemisphere of the spinal cord (T12) was hemisected in the SCI group. The hindlimb representations of the sensory cortex in both groups were imaged bilaterally on the day before (0d), and three days (3d), two weeks (2w), and one month (1m) after the SCI. The rates of stable, newly formed, and eliminated spines were calculated by comparing images of individual dendritic spine in the same areas at different time points. In comparison to the control group, the rate of newly formed spines in the contralateral sensory cortex of the SCI group increased at three days and two weeks after injury. The rates of eliminated spines in the bilateral sensory cortices increased and the rate of stable spines in the bilateral cortices declined at two weeks and one month. From three days to two weeks, the stable rates of bilaterally stable spines in the SCI group decreased. In comparison to the control group and contralateral cortex in the SCI group, the re-emerging rate of eliminated spines in ipsilateral cortex of the SCI group decreased significantly. The stable rates of newly formed spines in bilateral cortices of the SCI group decreased from two weeks to one month. We found that the remodeling in the hindlimb representation of the sensory cortex after spinal cord hemisection occurred bilaterally. This remodeling included eliminating spines and forming new spines, as well as changing the reorganized regions of the brain cortex after the SCI over time. Soon after the SCI, the cortex was remodeled by increasing spine formation in the contralateral cortex. Then it was remodeled prominently by eliminating spines of bilateral cortices. Spinal cord hemisection also caused traditional stable spines to become unstable and led the eliminated spines even more hard to recur especially in the ipsilateral cortex of the SCI group. In addition, it also made the new formed spines unstable.

We have previously demonstrated the growth-promoting effect of intrathecal delivery of recombinant rat IL-6 immediately after corticospinal tract (CST) injury. Our present study aims to further clarify whether intrathecal delivery of IL-6 after CST injury could reactivate the intrinsic growth capacity of pyramidal cells in the sensorimotor cortex which project long axons to the spinal cord. We examined, by ELISA, levels of cyclic adenosine monophosphate (cAMP), adenylyl cyclase (AC, which synthesizes cAMP), phosphodiesterases (PDE, which degrades cAMP), and, by RT-PCR, the expression of regeneration-associated genes in the rat sensorimotor cortex after intrathecal delivery of IL-6 for 7 days, started immediately after CST injury. Furthermore, we injected retrograde neuronal tracer Fluorogold (FG) to the spinal cord to label pyramidal cells in the sensorimotor cortex, layers V and VI, combined with βIII-tubulin immunostaining, then we analyzed by immunohistochemisty and western blot the expression of the co-receptor gp-130 of IL-6 family, and pSTAT3 and mTOR, downstream IL-6/JAK/STAT3 and PI3K/AKT/mTOR signaling pathways respectively. We showed that intrathecal delivery of IL-6 elevated cAMP level and upregulated the expression of regeneration-associated genes including GAP-43, SPRR1A, CAP-23 and JUN-B, and the expression of pSTAT3 and mTOR in pyramidal cells of the sensorimotor cortex. In contrast, AG490, an inhibitor of JAK, partially blocked these effects of IL-6. All these results indicate that intrathecal delivery of IL-6 immediately after spinal cord injury can reactivate the intrinsic growth capacity of pyramidal cells in the sensorimotor cortex and these effects of IL-6 were partially JAK/STAT3-dependent.

Background: Recovery following stroke depends on cellular plasticity in the perilesional zone (PZ). Doublecortin (DCX), a protein mainly labeling immature neurons in neurogenic niches is also highly expressed in the vicinity of focal cortical infarcts. Notably, the number of DCX+ cells positively correlates with the recovery of functional deficits after stroke though the nature and origin of these cells remains unclear., Results: In the present study, we aimed to characterize the population of DCX+ cells in the vicinity of ischemic infarcts in a mouse model in detail. Employing a photothrombosis model, distinct immunohistochemical techniques, stereology and confocal microscopy, we show that: i) DCX+ cells in the perilesional zone do not constitute a homogenous population and two cell types, stellate and polar cells can be distinguished according to their morphology. ii) Stellate cells are mainly located in the lateral and medial vicinity of the insult and express astrocytic markers. iii) Polar cells are found almost exclusively in the corpus callosum region including in the preserved deep cortical layers close to the subventricular zone (SVZ). Further, they do not show any colocalisation of glial markers. Polar morphology and distribution suggest a migration towards the lesion., Conclusions: In summary, our findings provide evidence that in mice DCX+ cells in the perilesional zone of cortical infarcts comprise a distinct cell population and the majority of cells are of glial nature.

Background and Purpose: Diffusion MRI is a promising, clinically feasible imaging technique commonly used to describe white matter changes after stroke. We investigated the sensitivity of diffusion MRI to detect microstructural alterations in gray matter after sensorimotor cortex stroke in adult male rats., Methods: The mean diffusivity (MD) and mean kurtosis of perilesional motor cortex were compared with measures in the contralesional forelimb area of sensorimotor cortex at 2 hours, 24 hours, 72 hours, or 25 days after surgery. MD and mean kurtosis were correlated to the surface densities of glia, dendrites, and axons., Results: Perilesional mean kurtosis was increased at 72 hours and 25 days after stroke, whereas MD was no longer different from contralesional sensorimotor cortex at 24 hours after stroke. There was a significant increase in the density of glial processes at 72 hours after stroke in perilesional motor cortex, which correlated with perilesional MD., Conclusions: These data support that mean kurtosis and MD provide different but complimentary information on acute and chronic changes in perilesional cortex. Glia infiltration is associated with pseudonormalization of MD in the perilesional motor cortex at 72 hours after lesion; however, this association is absent 25 days after lesion. These data suggest that there are likely several different, time-specific microstructural changes underlying these 2 complimentary diffusion measures., (© 2015 American Heart Association, Inc.)

To determine whether the exposure to long term enriched environment (EE) would result in a continuous improvement of neurological recovery and ameliorate the loss of brain tissue after traumatic brain injury (TBI) vs. standard housing (SH). Male Sprague-Dawley rats (300-350 g, n=28) underwent lateral fluid percussion brain injury or SHAM operation. One TBI group was held under complex EE for 90 days, the other under SH. Neuromotor and sensorimotor dysfunction and recovery were assessed after injury and at days 7, 15, and 90 via Composite Neuroscore (NS), RotaRod test, and Barnes Circular Maze (BCM). Cortical tissue loss was assessed using serial brain sections. After day 7 EE animals showed similar latencies and errors as SHAM in the BCM. SH animals performed notably worse with differences still significant on day 90 (p<0.001). RotaRod test and NS revealed superior results for EE animals after day 7. The mean cortical volume was significantly higher in EE vs. SH animals (p=0.003). In summary, EE animals after lateral fluid percussion (LFP) brain injury performed significantly better than SH animals after 90 days of recovery. The window of opportunity may be wide and also lends further credibility to the importance of long term interventions in patients suffering from TBI.

Pseudopheochromocytoma is a poorly understood, rare cause of severe paroxysmal hypertension that mimics the symptomatology of pheochromocytoma in the absence of biochemical evidence of this tumor. Symptoms such as headache, nausea, sweating, and palpitations during hypertensive episodes have been described. In this paper, we describe previously unreported findings of lateralizing sensorimotor deficits in a patient with pseudopheochromocytoma. These changes presented during a hypertensive episode and were concerning for stroke but were not accompanied by acute radiologic abnormalities. The deficits improved over 1.5 weeks as blood pressure stabilized with beta-blockade. We also review relevant literature on the clinical features, pathophysiology, and management of pseudopheochromocytoma.

Intranasal treatment with C57BL/6 MSCs reduces lesion volume and improves motor and cognitive behavior in the neonatal hypoxic-ischemic (HI) mouse model. In this study, we investigated the potential of human MSCs (hMSCs) to treat HI brain injury in the neonatal mouse. Assessing the regenerative capacity of hMSCs is crucial for translation of our knowledge to the clinic. We determined the neuroregenerative potential of hMSCs in vitro and in vivo by intranasal administration 10 d post-HI in neonatal mice. HI was induced in P9 mouse pups. 1×10(6) or 2×10(6) hMSCs were administered intranasally 10 d post-HI. Motor behavior and lesion volume were measured 28 d post-HI. The in vitro capacity of hMSCs to induce differentiation of mouse neural stem cell (mNSC) was determined using a transwell co-culture differentiation assay. To determine which chemotactic factors may play a role in mediating migration of MSCs to the lesion, we performed a PCR array on 84 chemotactic factors 10 days following sham-operation, and at 10 and 17 days post-HI. Our results show that 2×10(6) hMSCs decrease lesion volume, improve motor behavior, and reduce scar formation and microglia activity. Moreover, we demonstrate that the differentiation assay reflects the neuroregenerative potential of hMSCs in vivo, as hMSCs induce mNSCs to differentiate into neurons in vitro. We also provide evidence that the chemotactic factor CXCL10 may play an important role in hMSC migration to the lesion site. This is suggested by our finding that CXCL10 is significantly upregulated at 10 days following HI, but not at 17 days after HI, a time when MSCs no longer reach the lesion when given intranasally. The results described in this work also tempt us to contemplate hMSCs not only as a potential treatment option for neonatal encephalopathy, but also for a plethora of degenerative and traumatic injuries of the nervous system.

Aim: This investigation used magnetoencephalography (MEG) to examine the neural oscillatory responses of the sensorimotor cortices during the motor planning and movement execution stages of children with typical development and children with cerebral palsy (CP)., Method: The study involved 13 children with CP (nine males, four females; mean [SD] age 14y 3mo [9mo], range 10-18y; height 1.61m [0.08m]; weight 52.65kg [13kg]), and 13 age- and sex-matched typically developing children (height 1.64m [0.06m]; weight 56.88kg [10kg]). The experiment required the children to extend their knee joint as whole-head MEG recordings were acquired. Beamformer imaging methods were employed to quantify the source activity of the beta-frequency (14-28Hz) event-related desynchronization (ERD) that occurs during the motor planning period, and the gamma-frequency (~50Hz) event-related synchronization (ERS) that occurs at the motor execution stage., Results: The children with CP had a stronger mean beta ERD during the motor planning phase and reduced mean gamma ERS at the onset of movement., Interpretation: The uncharacteristic beta ERD in the children with CP suggests that they may have greater difficulty planning knee joint movements. We suggest that these aberrant beta ERD oscillations may have a cascading effect on the gamma ERS, which ultimately affects the execution of the motor command., (© 2014 Mac Keith Press.)

UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase is an α2β2γ2 hexameric enzyme that catalyzes the synthesis of the mannose 6-phosphate targeting signal on lysosomal hydrolases. Mutations in the α/β subunit precursor gene cause the severe lysosomal storage disorder mucolipidosis II (ML II) or the more moderate mucolipidosis III alpha/beta (ML III α/β), while mutations in the γ subunit gene cause the mildest disorder, mucolipidosis III gamma (ML III γ). Here we report neurologic consequences of mouse models of ML II and ML III γ. The ML II mice have a total loss of acid hydrolase phosphorylation, which results in depletion of acid hydrolases in mesenchymal-derived cells. The ML III γ mice retain partial phosphorylation. However, in both cases, total brain extracts have normal or near normal activity of many acid hydrolases reflecting mannose 6-phosphate-independent lysosomal targeting pathways. While behavioral deficits occur in both models, the onset of these changes occurs sooner and the severity is greater in the ML II mice. The ML II mice undergo progressive neurodegeneration with neuronal loss, astrocytosis, microgliosis and Purkinje cell depletion which was evident at 4 months whereas ML III γ mice have only mild to moderate astrocytosis and microgliosis at 12 months. Both models accumulate the ganglioside GM2, but only ML II mice accumulate fucosylated glycans. We conclude that in spite of active mannose 6-phosphate-independent targeting pathways in the brain, there are cell types that require at least partial phosphorylation function to avoid lysosomal dysfunction and the associated neurodegeneration and behavioral impairments.

Objective: Herein we present a single-center retrospective study of patients who underwent epilepsy surgery for seizures arising from the sensorimotor (rolandic) cortex. The goal was to find prognostic factors associated with better seizure outcome and to evaluate both surgical and neurologic outcomes., Patients, Methods, and Materials: A total of 66 patients fulfilled eligibility criteria and were included in the study. Patients were divided into two groups for analysis: patients with resections within rolandic cortex (RO group; n = 46), and patients with resections in immediate perirolandic cortex and simultaneous sensorimotor multiple subpial transections (IPR group; n = 20)., Results: Favorable postoperative seizure outcome (International League Against Epilepsy [ILAE]; ILAE1-ILAE3) was achieved in 42 patients (64%), 39 (59%) of whom were completely seizure-free (ILAE1). The favorable seizure outcome in the RO group (72%) was better than in the IPR group (45%) (p = 0.04, relative risk [RR] 0.51 [0.28-0.94, 95% CI]). Eighteen patients (34%) had a postoperative permanent neurologic deficit. Independent predictors for excellent seizure outcome (ILAE1) after multivariate regression analysis were complete resection of the lesion (p < 0.001), pathology (p = 0.009), age at surgery (p = 0.03), and the absence of preoperative simple partial seizures (p = 0.01)., Significance: With a 64% favorable seizure outcome, surgery for intractable epilepsy arising from sensorimotor cortex is possible and can be worthwhile. The increased risk for postoperative neurologic deficits is higher than in other locations, and this must be discussed with patients in detail prior to surgery. Best postoperative results can be achieved in cases in which a complete resection is possible without damaging eloquent cortical areas., (Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.)

The primate corticospinal tract (CST), the major descending pathway mediating voluntary hand movements, comprises nine or more functional subdivisions. The role of subcomponents other than that from primary motor cortex, however, is not well understood. We have previously shown that following a cervical dorsal rhizotomy (Darian-Smith et al., 2013), CST projections originating from primary somatosensory (S1) and motor (M1) cortex responded quite differently to injury. Terminal projections from the S1 (areas 3b/1/2) shrank to <60% of the contralateral side, while M1 CST projections remained robust or expanded (>110%). Here, we asked what happens when a central lesion is added to the equation, to better simulate clinical injury. Monkeys (n = 6) received either a unilateral (1) dorsal root lesion (DRL), (2) or a combined DRL/dorsal column lesion (DRL/DCL), or (3) a DRL/DCL where the DCL was made 4 months following the initial DRL. Electrophysiological recordings were made in S1 4 months postlesion in the first two groups, and 6 weeks after the DCL in the third lesion group, to identify the reorganized region of D1-D3 (thumb, index finger, and middle finger) representation. Anterograde tracers were then injected bilaterally to assess spinal terminal labeling. Remarkably, in all DRL/DCL animals, terminal projections from the S1 and M1 extended bilaterally and caudally well beyond terminal territories in normal animals or following a DRL. These data were highly significant. Extensive sprouting from the S1 CST has not been reported previously, and these data raise important questions about S1 CST involvement in recovery following spinal injury., (Copyright © 2014 the authors 0270-6474/14/3312267-13$15.00/0.)

Decreases in metabolites and increased motor-related, but decreased sensory-related activation of the sensorimotor cortex (SMC) have been observed in patients with cervical myelopathy (CM) using advanced MRI techniques. However, the nature of intrinsic neuronal activity in the SMC, and the relationship between cerebral function and structural damage of the spinal cord in patients with CM are not fully understood. The purpose of this study was to assess intrinsic neuronal activity by calculating the regional amplitude of low frequency fluctuations (ALFF) using resting-state functional MRI (rs-fMRI), and correlations with clinical and imaging indices. Nineteen patients and 19 age- and sex-matched healthy subjects underwent rs-fMRI scans. ALFF measurements were performed in the SMC, a key brain network likely to impaired or reorganized patients with CM. Compared with healthy subjects, increased amplitude of cortical low-frequency oscillations (LFO) was observed in the right precentral gyrus, right postcentral gyrus, and left supplementary motor area. Furthermore, increased z-ALFF values in the right precentral gyrus and right postcentral gyrus correlated with decreased fractional anisotropy values at the C2 level, which indicated increased intrinsic neuronal activity in the SMC corresponding to the structural impairment in the spinal cord of patients with CM. These findings suggest a complex and diverging relationship of cortical functional reorganization and distal spinal anatomical compression in patients with CM and, thus, add important information in understanding how spinal cord integrity may be a factor in the intrinsic covariance of spontaneous low-frequency fluctuations of BOLD signals involved in cortical plasticity.

Cerebral palsy (CP) is characterized by difficulty in control of movement and posture due to brain damage during early development. In addition, tactile discrimination deficits are prevalent in CP. To study the function of somatosensory and motor systems in CP, we compared the reactivity of sensorimotor cortical oscillations to median nerve stimulation in 12 hemiplegic CP children vs. 12 typically developing children using magnetoencephalography. We also determined the primary cortical somatosensory and motor representation areas of the affected hand in the CP children using somatosensory-evoked magnetic fields and navigated transcranial magnetic stimulation, respectively. We hypothesized that the reactivity of the sensorimotor oscillations in alpha (10 Hz) and beta (20 Hz) bands would be altered in CP and that the beta-band reactivity would depend on the individual pattern of motor representation. Accordingly, in children with CP, suppression and rebound of both oscillations after stimulation of the contralateral hand were smaller in the lesioned than intact hemisphere. Furthermore, in two of the three children with CP having ipsilateral motor representation, the beta- but not alpha-band modulations were absent in both hemispheres after affected hand stimulation suggesting abnormal sensorimotor network interactions in these individuals. The results are consistent with widespread alterations in information processing in the sensorimotor system and complement current understanding of sensorimotor network development after early brain insults. Precise knowledge of the functional sensorimotor network organization may be useful in tailoring individual rehabilitation for people with CP., (Copyright © 2014 Wiley Periodicals, Inc.)

High-frequency stimulation of the subthalamic nucleus (STN-HFS) is widely used as therapeutic intervention in patients suffering from advanced Parkinson's disease. STN-HFS exerts a powerful modulatory effect on cortical motor control by orthodromic modulation of basal ganglia outflow and via antidromic activation of corticofugal fibers. However, STN-HFS-induced changes of the sensorimotor cortex are hitherto unexplored. To address this question at a genomic level, we performed mRNA expression analyses using Affymetrix microarray gene chips and real-time RT-PCR in sensorimotor cortex of parkinsonian and control rats following STN-HFS. Experimental parkinsonism was induced in Brown Norway rats by bilateral nigral injections of 6-hydroxydopamine and was assessed histologically, behaviorally, and electrophysiologically. We applied prolonged (23h) unilateral STN-HFS in awake and freely moving animals, with the non-stimulated hemisphere serving as an internal control for gene expression analyses. Gene enrichment analysis revealed strongest regulation in major histocompatibility complex (MHC) related genes. STN-HFS led to a cortical downregulation of several MHC class II (RT1-Da, Db1, Ba, and Cd74) and MHC class I (RT1CE) encoding genes. The same set of genes showed increased expression levels in a comparison addressing the effect of 6-hydroxydopamine lesioning. Hence, our data suggest the possible association of altered microglial activity and synaptic transmission by STN-HFS within the sensorimotor cortex of 6-hydroxydopamine treated rats.

Introduction: Rolandic epilepsy (RE) is a childhood epilepsy with centrotemporal (rolandic) spikes, that is increasingly associated with language impairment. In this study, we tested for a white matter (connectivity) correlate, employing diffusion weighted MRI and language testing., Methods: Twenty-three children with RE and 23 matched controls (age: 8-14 years) underwent structural (T1-weighted) and diffusion-weighted MRI (b = 1200 s/mm(2), 66 gradient directions) at 3T, as well as neuropsychological language testing. Combining tractography and a cortical segmentation derived from the T1-scan, the rolandic tract were reconstructed (pre- and postcentral gyri), and tract fractional anisotropy (FA) values were compared between patients and controls. Aberrant tracts were tested for correlations with language performance., Results: Several reductions of tract FA were found in patients compared to controls, mostly in the left hemisphere; the most significant effects involved the left inferior frontal (p = 0.005) and supramarginal (p = 0.004) gyrus. In the patient group, lower tract FA values were correlated with lower language performance, among others for the connection between the left postcentral and inferior frontal gyrus (p = 0.043, R = 0.43)., Conclusion: In RE, structural connectivity is reduced for several connections involving the rolandic regions, from which the epileptiform activity originates. Most of these aberrant tracts involve the left (typically language mediating) hemisphere, notably the pars opercularis of the inferior frontal gyrus (Broca's area) and the supramarginal gyrus (Wernicke's area). For the former, reduced language performance for lower tract FA was found in the patients. These findings provide a first microstructural white matter correlate for language impairment in RE.