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Background: Paramagnetic rim white matter (WM) lesions (PRL) are thought to be a main driver of non-relapsing multiple sclerosis (MS) progression. It is unknown whether cerebrospinal fluid (CSF)-soluble factors diffusing from the ventricles contribute to PRL formation. Objective: To investigate the distribution of PRL and non-rim brain WM lesions as a function of distance from ventricular CSF, their relationship with cortical lesions, the contribution of lesion phenotype, and localization to neurological disability. Methods: Lesion count and volume of PRL, non-rim WM, leukocortical lesion (LCL), and subpial/intracortical lesions were obtained at 7-T. The brain WM was divided into 1-mm-thick concentric rings radiating from the ventricles to extract PRL and non-rim WM lesion volume from each ring. Results: In total, 61 MS patients with ⩾1 PRL were included in the study. Both PRL and non-rim WM lesion volumes were the highest in the periventricular WM and declined with increasing distance from ventricles. A CSF distance-independent association was found between non-rim WM lesions, PRL, and LCL, but not subpial/intracortical lesions. Periventricular non-rim WM lesion volume was the strongest predictor of neurological disability. Conclusions: Non-rim and PRL share a gradient of distribution from the ventricles toward the cortex, suggesting that CSF proximity equally impacts the prevalence of both lesion phenotypes. [ABSTRACT FROM AUTHOR]

Background: Not only gray matter lesions (GMLs) but also white matter lesions (WMLs) can play important roles in the pathology of Alzheimer's disease (AD). The progression of cognitive impairment (CI) and behavioral and psychological symptoms of dementia (BPSD) might be caused by a concerted effect of both GML and WML. Objective: This study aimed to investigate the association between GML and WML and how they are involved in the symptoms of CI and BPSD in dementia patients by means of imaging technology. Methods: Patients in our memory clinic, who were diagnosed with AD-type dementia or amnestic mild cognitive impairment (aMCI) and had undergone both single-photon emission computed tomography (SPECT) and brain MRI, were consecutively enrolled (n = 156; 61 males and 95 females; 79.8 ± 7.4 years old). Symptoms of CI and BPSD were obtained from patients' medical records. For the analysis of GMLs and WMLs, SPECT data and MRI T1-weighted images were used, respectively. This study followed the Declaration of Helsinki, and all procedures were approved by the institutional ethics committee. Results: According to a multivariate analysis, disorientation and disturbed attention demonstrated a relationship between the precuneus and WMLs in both hemispheres. Hyperactivity in BPSD showed multiple correlations between GMLs on both sides of the frontal cortex and WMLs. Patients with aMCI presented more multiple correlations between GMLs and WMLs compared with those with AD-type dementia regarding dementia symptoms including BPSD. Conclusion: The interaction between GMLs and WMLs may vary depending on the symptoms of CI and BPSD. Hyperactivity in BPSD may be affected by the functional relationship between GMLs and WMLs in the left and right hemispheres. The correlation between GMLs and WMLs may be changing in AD-type dementia and aMCI. [ABSTRACT FROM AUTHOR]

Background: Not only gray matter lesions (GMLs) but also white matter lesions (WMLs) can play important roles in the pathology of Alzheimer’s disease (AD). The progression of cognitive impairment (CI) and behavioral and psychological symptoms of dementia (BPSD) might be caused by a concerted effect of both GML and WML. Objective: This study aimed to investigate the association between GML and WML and how they are involved in the symptoms of CI and BPSD in dementia patients by means of imaging technology. Methods: Patients in our memory clinic, who were diagnosed with AD-type dementia or amnestic mild cognitive impairment (aMCI) and had undergone both single-photon emission computed tomography (SPECT) and brain MRI, were consecutively enrolled (n = 156; 61 males and 95 females; 79.8 ± 7.4 years old). Symptoms of CI and BPSD were obtained from patients’ medical records. For the analysis of GMLs and WMLs, SPECT data and MRI T1-weighted images were used, respectively. This study followed the Declaration of Helsinki, and all procedures were approved by the institutional ethics committee. Results: According to a multivariate analysis, disorientation and disturbed attention demonstrated a relationship between the precuneus and WMLs in both hemispheres. Hyperactivity in BPSD showed multiple correlations between GMLs on both sides of the frontal cortex and WMLs. Patients with aMCI presented more multiple correlations between GMLs and WMLs compared with those with AD-type dementia regarding dementia symptoms including BPSD. Conclusion: The interaction between GMLs and WMLs may vary depending on the symptoms of CI and BPSD. Hyperactivity in BPSD may be affected by the functional relationship between GMLs and WMLs in the left and right hemispheres. The correlation between GMLs and WMLs may be changing in AD-type dementia and aMCI.

Focal cortical dysplasia (FCD) is a malformation of cortical development that is a prevalent cause of intractable epilepsy in children. Of the three FCD subtypes, understanding the etiology and pathogenesis of FCD type II has seen the most progress owing to the recent advances in identifying gene mutations along the mTOR signaling pathway as a frequent cause of this disorder. Accordingly, numerous animal models of FCD type II based on genetic manipulation of the mTOR signaling pathway have emerged to investigate the mechanisms of epileptogenesis and novel therapeutics for epilepsy. These include transgenic and in utero electroporation-based animal models. Here, we review the histopathological and electroclinical features of existing FCD type II animal models and discuss the scientific and technical considerations, clinical applications, and limitations of current models. We also highlight other models of FCD based on early life acquired factors. [ABSTRACT FROM AUTHOR]

Background: Technical improvements in magnetic resonance imaging (MRI) acquisition, such as higher field strength and optimized sequences, lead to better multiple sclerosis (MS) lesion detection and characterization. Multiplication of 3D-FLAIR with 3D-T2 sequences (FLAIR2) results in isovoxel images with increased contrast-to-noise ratio, increased white–gray-matter contrast, and improved MS lesion visualization without increasing MRI acquisition time. The current study aims to assess the potential of 3D-FLAIR2 in detecting cortical/leucocortical (LC), juxtacortical (JC), and white matter (WM) lesions. Objective: To compare lesion detection of 3D-FLAIR2 with state-of-the-art 3D-T2-FLAIR and 3D-T2-weighted images. Methods: We retrospectively analyzed MRI scans of thirteen MS patients, showing previously noted high cortical lesion load. Scans were acquired using a 3 T MRI scanner. WM, JC, and LC lesions were manually labeled and manually counted after randomization of 3D-T2, 3D-FLAIR, and 3D-FLAIR2 scans using the ITK-SNAP tool. Results: LC lesion visibility was significantly improved by 3D-FLAIR2 in comparison to 3D-FLAIR (4 vs 1; p = 0.018) and 3D-T2 (4 vs 1; p = 0.007). Comparing LC lesion detection in 3D-FLAIR2 vs. 3D-FLAIR, 3D-FLAIR2 detected on average 3.2 more cortical lesions (95% CI − 9.1 to 2.8). Comparing against 3D-T2, 3D-FLAIR2 detected on average 3.7 more LC lesions (95% CI 3.3–10.7). Conclusions: 3D-FLAIR2 is an easily applicable time-sparing MR post-processing method to improve cortical lesion detection. Larger sampled studies are warranted to validate the sensitivity and specificity of 3D-FLAIR2. [ABSTRACT FROM AUTHOR]

Background: Precise detection and classification of intracortical (IC) lesions in multiple sclerosis (MS) patients are very important for understanding their role in disease progression and determining their effects on the clinical presentations of the disease. Objectives: This study aimed to evaluate the efficacy of phase-sensitive inversion recovery (PSIR) in delineation of cortical lesions in MS patients. Patients and Methods: This cross-sectional, single-center study was performed among 38 patients with the mean age of 31 years, who were recruited from December 2018 to August 2020. All MS patients underwent magnetic resonance imaging (MRI), using a 1.5-Tesla scanner. Two expert neuroradiologists interpreted the fluid-attenuated inversion recovery (FLAIR), T2-weighted turbo spin echo (T2W-TSE), and PSIR images. The lesions were classified as purely IC, mixed gray/white matter (WM) [leukocortical (LC)], and juxtacortical (JC). The number of lesions in each region was compared between the FLAIR, T2W-TSE, and PSIR sequences. Results: The number of cortical lesions (IC and LC) was significantly higher in PSIR compared to T2W-TSE and Fluid attenuated inversion recovery (FLAIR) (P < 0.001), while the number of JC lesions was lower; in other words, the mean number of plaques was higher in T2W-TSE and FLAIR as compared to PSIR. Conclusion: The PSIR sequence significantly improved the delineation of cortical lesions and could be useful in monitoring cortical injuries and disease progression in MS patients. [ABSTRACT FROM AUTHOR]

Individual differences in learning capacity are evident in humans and most other animals. Traditionally, such differences are described in terms of variations along a relatively small number of psychological dimensions corresponding to behavioral traits. Here, an alternative approach is considered in which individual differences in learning capacity are characterized by spatially sorting behavioral patterns. To illustrate this approach, a two-dimensional self-organizing feature map wasused to analyze patterns in the performances of intact and cortically-lesioned rats engaged in multiple learning tasks. After training, the spatial structure of the map revealed systematic variations inlearning across rats that were related to the degree of brain damage. Individual nodes within the map described prototypical performance profiles that corresponded closely to patterns of learning seen in individual rats, including individuals with idiosyncratic profiles. Techniques that automatically identify modal patterns of performance during learning may provide new insights into the processes that determine what an individual organism can learn.

We previously reported that embryonic motor cortical neurons transplanted 1-week after lesion in the adult mouse motor cortex significantly enhances graft vascularization, survival, and proliferation of grafted cells, the density of projections developed by grafted neurons and improves functional repair and recovery. The purpose of the present study is to understand the extent to which post-traumatic inflammation following cortical lesion could influence the survival of grafted neurons and the development of their projections to target brain regions and conversely how transplanted cells can modulate host inflammation. For this, embryonic motor cortical tissue was grafted either immediately or with a 1-week delay into the lesioned motor cortex of adult mice. Immunohistochemistry (IHC) analysis was performed to determine the density and cell morphology of resident and peripheral infiltrating immune cells. Then, in situ hybridization (ISH) was performed to analyze the distribution and temporal mRNA expression pattern of pro-inflammatory or anti-inflammatory cytokines following cortical lesion. In parallel, we analyzed the protein expression of both M1- and M2-associated markers to study the M1/M2 balance switch. We have shown that 1-week after the lesion, the number of astrocytes, microglia, oligodendrocytes, and CD45+ cells were significantly increased along with characteristics of M2 microglia phenotype. Interestingly, the majority of microglia co-expressed transforming growth factor-β1 (TGF-β1), an anti-inflammatory cytokine, supporting the hypothesis that microglial activation is also neuroprotective. Our results suggest that the modulation of post-traumatic inflammation 1-week after cortical lesion might be implicated in the improvement of graft vascularization, survival, and density of projections developed by grafted neurons.

We previously reported that embryonic motor cortical neurons transplanted 1-week after lesion in the adult mouse motor cortex significantly enhances graft vascularization, survival, and proliferation of grafted cells, the density of projections developed by grafted neurons and improves functional repair and recovery. The purpose of the present study is to understand the extent to which post-traumatic inflammation following cortical lesion could influence the survival of grafted neurons and the development of their projections to target brain regions and conversely how transplanted cells can modulate host inflammation. For this, embryonic motor cortical tissue was grafted either immediately or with a 1-week delay into the lesioned motor cortex of adult mice. Immunohistochemistry (IHC) analysis was performed to determine the density and cell morphology of resident and peripheral infiltrating immune cells. Then, in situ hybridization (ISH) was performed to analyze the distribution and temporal mRNA expression pattern of pro-inflammatory or anti-inflammatory cytokines following cortical lesion. In parallel, we analyzed the protein expression of both M1- and M2-associated markers to study the M1/M2 balance switch. We have shown that 1-week after the lesion, the number of astrocytes, microglia, oligodendrocytes, and CD45+ cells were significantly increased along with characteristics of M2 microglia phenotype. Interestingly, the majority of microglia co-expressed transforming growth factor-β1 (TGF-β1), an anti-inflammatory cytokine, supporting the hypothesis that microglial activation is also neuroprotective. Our results suggest that the modulation of post-traumatic inflammation 1-week after cortical lesion might be implicated in the improvement of graft vascularization, survival, and density of projections developed by grafted neurons. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency of cortical lesions (CLs) in patients with pediatric-onset multiple sclerosis (POMS) using multi-contrast magnetic resonance imaging (MRI), and the relationship between frontal CL load and upper limb dexterity assessed with the Nine-Hole Peg Test (9-HPT). Methods: Participants completed the 9-HPT and were imaged on a 3T MRI scanner to collect T1-weighted three-dimensional (3D) magnetization prepared rapid gradient echo (MPRAGE), proton density–weighted, T2-weighted and fluid-attenuated inversion recovery (FLAIR) images. CLs were manually segmented using all MRI contrasts. Results: We enrolled 24 participants with POMS (mean (standard deviation) age at first symptom: 13.3 (±2.7) years; mean age at scan: 18.8 (±3) years; mean disease duration of 5 (±3.2) years). A total of 391 CLs (mean, 16.3 ± 27.2; median, 7) were identified in 19 of 24 POMS patients (79%). The total number of CLs was positively associated with white matter lesion volume (p = 0.04) but not with thalamic volume, age at the time of the scan, or disease duration. The number of frontal CLs was associated with slower performance on the 9-HPT (p = 0.05). Conclusion: Multi-contrast 3T MRI led to a high rate of CL detection, demonstrating that cortical pathology occurs even in pediatric-onset disease. Frontal lobe CL count was associated with reduced manual dexterity, indicating that these CLs are clinically relevant. [ABSTRACT FROM AUTHOR]

The corticotectal projections, together with the corticobulbar (corticoreticular) projections, work in parallel with the corticospinal tract (CST) to influence motoneurons in the spinal cord both directly and indirectly via the brainstem descending pathways. The tectospinal tract (TST) originates in the deep layers of the superior colliculus. In the present study, we analyzed the corticotectal projections from two motor cortical areas, namely the premotor cortex (PM) and the primary motor cortex (M1) in eight macaque monkeys subjected to either a cortical lesion of the hand area in M1 (n = 4) or Parkinson's disease-like symptoms PD (n = 4). A subgroup of monkeys with cortical lesion was subjected to anti-Nogo-A antibody treatment whereas all PD monkeys were transplanted with Autologous Neural Cell Ecosystems (ANCEs). The anterograde tracer BDA was used to label the axonal boutons both en passant and terminaux in the ipsilateral superior colliculus. Individual axonal boutons were charted in the different layers of the superior colliculus. In intact animals, we previously observed that corticotectal projections were denser when originating from PM than from M1. In the present M1 lesioned monkeys, as compared to intact ones the corticotectal projection originating from PM was decreased when treated with anti-Nogo-A antibody but not in untreated monkeys. In PD-like symptoms' monkeys, on the other hand, there was no consistent change affecting the corticotectal projection as compared to intact monkeys. The present pilot study overall suggests that the corticotectal projection is less affected by M1 lesion or PD symptoms than the corticoreticular projection previously reported in the same animals. [ABSTRACT FROM AUTHOR]

Abstract Damage to the primary visual cortex (V1) leads to a visual field loss (scotoma) in the retinotopically corresponding part of the visual field. Nonetheless, a small amount of residual visual sensitivity persists within the blind field. This residual capacity has been linked to activity observed in the middle temporal area complex (V5/MT+). However, it remains unknown whether the organization of hV5/MT+ changes following early visual cortical lesions. We studied the organization of area hV5/MT+ of five patients with dense homonymous defects in a quadrant of the visual field as a result of partial V1+ or optic radiation lesions. To do so, we developed a new method, which models the boundaries of population receptive fields directly from the BOLD signal of each voxel in the visual cortex. We found responses in hV5/MT+ arising inside the scotoma for all patients and identified two possible sources of activation: 1) responses might originate from partially lesioned parts of area V1 corresponding to the scotoma, and 2) responses can also originate independent of area V1 input suggesting the existence of functional V1-bypassing pathways. Apparently, visually driven activity observed in hV5/MT+ is not sufficient to mediate conscious vision. More surprisingly, visually driven activity in corresponding regions of V1 and early extrastriate areas including hV5/MT+ did not guarantee visual perception in the group of patients with post-geniculate lesions that we examined. This suggests that the fine coordination of visual activity patterns across visual areas may be an important determinant of whether visual perception persists following visual cortical lesions. Highlights • We studied hV5/MT+ responses in patients with early visual cortical damage. • We developed a new population receptive field measurement method. • We found responses in hV5/MT+ arising inside the scotoma for all patients. • Responses in hV5/MT+ originate either from V1 or from V1-bypassing pathways. • Activity in either V1 and/or hV5/MT+ is not sufficient to mediate conscious vision. [ABSTRACT FROM AUTHOR]

A restricted lesion of the hand area in the primary motor cortex (Ml) leads to a deficit of contralesional manual dexterity, followed by an incomplete functional recovery, accompanied by plastic changes in Ml itself and in other cortical areas on both hemispheres. Using the marker SMI-32 specific to pyramidal neurons in cortical layers III and V, we investigated the impact of a focal unilateral Ml lesion (hand representation) on the rostral part (F6) and caudal part (F3) of the supplementary motor area (SMA) in both hemispheres in nine adult macaque monkeys compared with four intact control monkeys. The Ml lesion induced a consistent interhemispheric asymmetry in density of SMI-32-positive neurons in F3 layer V (statistically significant in 8 of 9 lesioned monkeys), highly correlated with the lesion volume and with the duration of functional recovery, but not with the extent of functional recovery itself. Such interhemispheric asymmetry was neither present in the intact monkeys, as expected, nor in F6 in all monkeys. In addition, the Ml lesion also impacted on the basal dendritic arborization of F3 layer V neurons. Neuronal density was clearly less affected by the Ml lesion in F3 layer III compared with layer V. We interpret the remote effect of Ml lesion onto the density of SMI-32-positive neurons and dendritic arborization in the SMAs bilaterally as the consequence of multiple factors, such as changes of connectivity, diaschisis and various mechanisms involved in cortical plasticity underlying the functional recovery from the Ml lesion. [ABSTRACT FROM AUTHOR]

Biomarkers specific to cortical gray matter (cGM) pathological changes of multiple sclerosis (MS) are desperately needed to better understand the disease progression. The cGM damage occurs in cortical lesion (CL) and normal-appearing cGM (NAcGM) areas. While the association between CL load and cGM damage has been reported, little is known about how different CL types, i.e. intracortical lesion (ICL) and leukocortical lesion (LCL) would be associated with cGM damage. In our study, relapsing-remitting MS patients and healthy controls were divided into 4 groups according to CL load level. NAcGM diffusion kurtosis imaging (DKI)/diffusion tensor imaging (DTI) values and cGM volume (cGMV) were used to characterize the pathological changes in cGM. Univariate general linear model was used for group comparisons and stepwise regression analysis was used to assess the effects of ICL volume and LCL volume on NAcGM damage. We found peak values in DKI/DTI values, cGMV and neuropsychological scores in high CL load group. Kurtosis fractional anisotropy (KFA) was the most sensitive in characterizing NAcGM damage, and LCL volume related more to NAcGM damage. Our findings suggested KFA could become a surrogate biomarker to cGM damage, and LCL might be the main factor in whole brain NAcGM damage., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Abstract: Functional recovery from central nervous system injury is likely to be partly due to a rearrangement of neural circuits. In this context, the corticobulbar (corticoreticular) motor projections onto different nuclei of the ponto‐medullary reticular formation (PMRF) were investigated in 13 adult macaque monkeys after either, primary motor cortex injury (MCI) in the hand area, or spinal cord injury (SCI) or Parkinson's disease‐like lesions of the nigro‐striatal dopaminergic system (PD). A subgroup of animals in both MCI and SCI groups was treated with neurite growth promoting anti‐Nogo‐A antibodies, whereas all PD animals were treated with autologous neural cell ecosystems (ANCE). The anterograde tracer BDA was injected either in the premotor cortex (PM) or in the primary motor cortex (M1) to label and quantify corticobulbar axonal boutons terminaux and en passant in PMRF. As compared to intact animals, after MCI the density of corticobulbar projections from PM was strongly reduced but maintained their laterality dominance (ipsilateral), both in the presence or absence of anti‐Nogo‐A antibody treatment. In contrast, the density of corticobulbar projections from M1 was increased following opposite hemi‐section of the cervical cord (at C7 level) and anti‐Nogo‐A antibody treatment, with maintenance of contralateral laterality bias. In PD monkeys, the density of corticobulbar projections from PM was strongly reduced, as well as that from M1, but to a lesser extent. In conclusion, the densities of corticobulbar projections from PM or M1 were affected in a variable manner, depending on the type of lesion/pathology and the treatment aimed to enhance functional recovery. [ABSTRACT FROM AUTHOR]

Background: Marchiafava-Bignami disease (MBD) is a neurological degenerative disorder with a pathognomonic hallmark of symmetric demyelination in the corpus callosum (CC). Most reported cases were chronic alcoholics and some showed cortical lesions related to poor clinical prognosis. Herein we report a case of a chronic alcoholic who presented with confusion and generalized weakness. Methods: Nerve fiber integrity and metabolic changes were evaluated with Magnetic resonance imaging (MRI) sequences including diffusion tensor imaging (DTI) and MRS. Results: MRI revealed the typical callosal lesions of MBD with bilateral frontoparietal cortical lesions. DTI and MRS showed both impaired myelin integrity and axonal density in the CC. The cortical lesions partly disappeared after intravenous administration of high-dose multivitamins and corticosteroids. The patient regained consciousness 3 months later while dysarthria and quadriplegia persisted. Three years later, the patient can interact occasionally with people and the functional activities of both upper and lower limbs have no improvement. Conclusions: To our knowledge, this is the first report of DTI together with MRS assisting in evaluating the prognosis of MBD. [ABSTRACT FROM AUTHOR]

Background: Cortical lesions (CLs) frequently observed in Caucasian patients with multiple sclerosis (MS) contribute to disability. However, it remains unclear whether CLs are associated with clinical features and genetic risk factors, such as HLA-DRB1*15:01 and -DRB1*04:05 in Asian MS patients. Objective: To elucidate the frequency of CLs and their association with HLA-DRB1 and DPB1 alleles in Japanese MS patients. Methods: Three-dimensional double inversion recovery imaging and clinical information were retrospectively obtained from 92 Japanese MS patients. Results: CLs of any type, intracortical lesions (ICLs), and leukocortical lesions (LCLs) were detected in 39.1%, 26.1%, and 28.3% of patients, respectively. MS patients with ICLs had a significantly higher frequency of secondary progression and greater Expanded Disability Status Scale (EDSS) scores than those without ICLs. Similar trends were observed with CLs and LCLs. The number of all three lesion types positively correlated with EDSS scores. The frequency and number of ICLs were significantly higher in HLA-DRB1*15:01 carriers than in HLA-DRB1*15:01 non-carriers, but significantly lower in HLA-DRB1*04:05 carriers than in HLA-DRB1*04:05 non-carriers. Multivariate logistic regression analysis revealed a negative association of HLA-DRB1*04:05 with ICLs. Conclusion: ICLs are associated with greater disease severity in Japanese MS patients and are partly suppressed by the HLA-DRB1*04:05 allele. [ABSTRACT FROM AUTHOR]

Vision is a very important sensory modality in humans. Visual disorders are numerous and arising from diverse and complex causes. Deficits in visual function are highly disabling from a social point of view and in addition cause a considerable economic burden. For all these reasons there is an intense effort by the scientific community to gather knowledge on visual deficit mechanisms and to find possible new strategies for recovery and treatment. In this review we focus on an important and sometimes neglected player of the visual function, the corpus callosum (CC). The CC is the major white matter structure in the brain and is involved in information processing between the two hemispheres. In particular, visual callosal connections interconnect homologous areas of visual cortices, binding together the two halves of the visual field. This interhemispheric communication plays a significant role in visual cortical output. Here, we will first review essential literature on the physiology of the callosal connections in normal vision. The available data support the view that the callosum contributes to both excitation and inhibition to the target hemisphere, with a dynamic adaptation to the strength of the incoming visual input. Next, we will focus on data showing how callosal connections may sense visual alterations and respond to the classical paradigm for the study of visual plasticity, i.e. monocular deprivation. This is a prototypical example of a model for the study of callosal plasticity in pathological conditions (e.g. strabismus and amblyopia) characterized by unbalanced input from the two eyes. We will also discuss findings of callosal alterations in blind subjects. Noteworthy, we will discuss data showing that inter-hemispheric transfer mediates recovery of visual responsiveness following cortical damage. Finally, we will provide an overview of how callosal projections dysfunction could contribute to pathologies such as neglect and occipital epilepsy. A particular focus will be on reviewing noninvasive brain stimulation techniques and optogenetic approaches that allow to selectively manipulate callosal function and to probe its involvement in cortical processing and plasticity. Overall, the data indicate that experience can potently impact on transcallosal connectivity, and that the callosum itself is crucial for plasticity

From a case study, we describe the impact of unilateral lesion of the hand area in the primary motor cortex (M1) on manual dexterity and the role of the intact contralesional M1 in long-term functional recovery. An adult macaque monkey performed two manual dexterity tasks: ( i ) “modified Brinkman board” task, assessed simple precision grip versus complex precision grip, the latter involved a hand postural adjustment; ( ii ) “modified Klüver board” task, assessed movements ranging from power grip to precision grip, pre-shaping and grasping. Two consecutive unilateral M1 lesions targeted the hand area of each hemisphere, the second lesion was performed after stable, though incomplete, functional recovery from the primary lesion. Following each lesion, the manual dexterity of the contralesional hand was affected in a comparable manner, effects being progressively more deleterious from power grip to simple and then complex precision grips. Both tasks yielded consistent data, namely that the secondary M1 lesion did not have a significant impact on the recovered performance from the primary M1 lesion, which took place 5 months earlier. In conclusion, the intact contralesional M1 did not play a major role in the long-term functional recovery from a primary M1 lesion targeted to the hand area. [ABSTRACT FROM AUTHOR]

The autoimmune disease multiple sclerosis (MS) is characterized by relapses in the majority of patients. A definitive clinical diagnosis of relapse in MS can be complicated by the presence of an infection or comorbid disorder. In this mini-review, we describe efforts to develop enhanced imaging techniques and biomarker detection as future tools for relapse validation. There is emerging evidence of roles for meningeal inflammation, sex hormones, comorbid metabolic or mood disorders, and a dysregulated immune profile in the manifestation and severity of relapse. Specific subsets of immune cells likely drive the pathophysiology of relapse, and identification of a patient's unique immunological signature of relapse may help guide future diagnosis and treatment. Finally, these studies highlight the diversity in terms of relapse presentation, immunological signature, and response in patients with MS, indicating that going forward the best approach to assessment and treatment of relapse will be multifactorial and highly personalized. [ABSTRACT FROM AUTHOR]

The role of different factors in influencing the risk of seizures during multiple sclerosis (MS) is not known. To perform a systematic review and meta-analysis of risk factors for epilepsy during MS. Pubmed, Google scholar, and Scopus databases were searched. Articles published in English (1986-2016) were included. Nine studies were included (3 retrospective cohort and 6 case-control) enrolling 2845 MS patients (217 with epilepsy; 7.6%). MS patients with epilepsy had a younger age at onset compared to MS patients without seizures (difference in means = -5.42 years, 95% CI -7.19 to -3.66, p < 0.001). Mean EDSS value at inclusion tended to be higher in patients with epilepsy, without reaching statistical significance (difference in means = 0.45, 95% CI -0.01 to 0.91, p = 0.054). No differences were observed in sex distribution (OR = 0.94, 95% CI 0.51-1.72, p = 0.83) and clinical form (OR = 1.03, 95% CI 0.33-3.21, p = 0.96). Two studies evaluated presence and number of cortical lesions as a risk factor for epilepsy in MS using different MRI techniques: in one study, cortical lesions were more frequently observed in patients with epilepsy (OR = 7.06, 95% CI 2.39-20.8; p < 0.001). In the other, cortico-juxtacortical lesions were more frequently observed in patients with epilepsy (OR = 2.6, 95% CI 1.0-6.5; p = 0.047). Studies about risk factors for epilepsy during MS are heterogeneous. Compared to MS patients without seizures, patients with epilepsy have an earlier MS onset and a higher EDSS score after similar disease duration. Clinical form of MS and sex do not predict the appearance of seizures. [ABSTRACT FROM AUTHOR]

Vision is a very important sensory modality in humans. Visual disorders are numerous and arising from diverse and complex causes. Deficits in visual function are highly disabling from a social point of view and in addition cause a considerable economic burden. For all these reasons there is an intense effort by the scientific community to gather knowledge on visual deficit mechanisms and to find possible new strategies for recovery and treatment. In this review, we focus on an important and sometimes neglected player of the visual function, the corpus callosum (CC). The CC is the major white matter structure in the brain and is involved in information processing between the two hemispheres. In particular, visual callosal connections interconnect homologous areas of visual cortices, binding together the two halves of the visual field. This interhemispheric communication plays a significant role in visual cortical output. Here, we will first review the essential literature on the physiology of the callosal connections in normal vision. The available data support the view that the callosum contributes to both excitation and inhibition to the target hemisphere, with a dynamic adaptation to the strength of the incoming visual input. Next, we will focus on data showing how callosal connections may sense visual alterations and respond to the classical paradigm for the study of visual plasticity, i.e., monocular deprivation (MD). This is a prototypical example of a model for the study of callosal plasticity in pathological conditions (e.g., strabismus and amblyopia) characterized by unbalanced input from the two eyes. We will also discuss the findings of callosal alterations in blind subjects. Noteworthy, we will discuss data showing that inter-hemispheric transfer mediates recovery of visual responsiveness following cortical damage. Finally, we will provide an overview of how callosal projections dysfunction could contribute to pathologies such as neglect and occipital epilepsy. A particular focus will be on reviewing noninvasive brain stimulation techniques and optogenetic approaches that allow to selectively manipulate callosal function and to probe its involvement in cortical processing and plasticity. Overall, the data indicate that experience can potently impact on transcallosal connectivity, and that the callosum itself is crucial for plasticity and recovery in various disorders of the visual pathway. [ABSTRACT FROM AUTHOR]

Background Multiple sclerosis can impair cognition from the early stages and has been shown to be associated with gray matter damage in addition to white matter pathology. Objectives To investigate the profile of cognitive impairment in clinically isolated syndrome (CIS), and the contribution of cortical inflammation, cortical and deep gray matter atrophy, and white matter lesions to cognitive decline. Methods Thirty patients with clinically isolated syndrome and twenty demographically- matched healthy controls underwent neuropsychologic assessment through the Rao Brief Repeatable Battery, and brain magnetic resonance imaging with double inversion recovery using a 3T scanner. Results Patients with clinically isolated syndrome performed significantly worse than healthy controls on tests that evaluated verbal memory, visuospatial learning and memory, and verbal fluency. Significant deep gray matter atrophy was found in the patients but cortical volume was not lower than the controls. Visual memory tests correlated with the volume of the hippocampus, cerebral white matter and deep gray matter structures and with cerebellar cortical atrophy. Cortical or white matter lesion load did not affect cognitive test results. Conclusion In our patients with CIS, it was shown that cognitive impairment was mainly related to cerebral white matter, cerebellar cortical and deep gray matter atrophy, but not with cortical inflammation, at least in the early stage of disease. [ABSTRACT FROM AUTHOR]

Highlights • Cortical involvement may exist in aquaporin-4-antibody-positive patients. • Conventional imaging is limited in evaluating cortical involvement. • Double inversion recovery imaging can help determine the location of the lesion. Abstract Background : Previous studies strongly suggested the absence of cortical involvement in neuromyelitis optica spectrum disorder. Methods : We describe two patients with anti-aquaporin-4 antibody and cortical lesions. Results : A 58-year-old and a 61-year-old woman presented with status epilepticus and right leg numbness, respectively. Double inversion recovery (DIR) and phase-sensitive inversion recovery (PSIR) imaging, magnetic resonance imaging sequences that enable the clear delineation of gray matter, revealed intracortical lesions and lesions located across the cortex and subcortex. Conclusion : Although rare, cortical involvement may exist in aquaporin-4 antibody-positive patients. DIR and PSIR MRI can help to determine the exact location of the lesion. [ABSTRACT FROM AUTHOR]