Brain communications最新文献

Damage to the primary visual cortex or its afferent white matter tracts results in loss of vision in the contralateral visual field that can present as homonymous visual field deficits. Evidence suggests that visual training in the blind field can partially reverse blindness at trained locations. However, the efficacy of visual training is highly variable across participants, and the reasons for this are poorly understood. It is likely that variance in residual neural circuitry following the insult may underlie the variation among patients. Many stroke survivors with visual field deficits retain residual visual processing in their blind field despite a lack of awareness. Previous research indicates that intact structural and functional connections between the dorsal lateral geniculate nucleus and the human extrastriate visual motion-processing area hMT+ are necessary for blindsight to occur. We therefore hypothesized that changes in this white matter pathway may underlie improvements resulting from motion discrimination training. Eighteen stroke survivors with long-standing, unilateral, homonymous field defects from retro-geniculate brain lesions completed 6 months of visual training at home. This involved performing daily sessions of a motion discrimination task, at two non-overlapping locations in the blind field, at least 5 days per week. Motion discrimination and integration thresholds, Humphrey perimetry and structural and diffusion-weighted MRI were collected pre- and post-training. Changes in fractional anisotropy (FA) were analysed in visual tracts connecting the ipsilesional dorsal lateral geniculate nucleus and hMT+, and the ipsilesional dorsal lateral geniculate nucleus and primary visual cortex. The (non-visual) tract connecting the ventral posterior lateral nucleus of the thalamus and the primary somatosensory cortex was analysed as a control. Changes in white matter integrity were correlated with improvements in motion discrimination and Humphrey perimetry. We found that the magnitude of behavioural improvement was not directly related to changes in FA in the pathway between the dorsal lateral geniculate nucleus and hMT+ or dorsal lateral geniculate nucleus and primary visual cortex. Baseline FA in either tract also failed to predict improvements in training. However, an exploratory analysis showed a significant increase in FA in the distal part of the tract connecting the dorsal lateral geniculate nucleus and hMT+, suggesting that 6 months of visual training in chronic, retro-geniculate strokes may enhance white matter microstructural integrity of residual geniculo-extrastriate pathways.

Damage to the primary visual cortex (V1) or its afferent white matter tracts results in loss of vision in the contralateral visual field that can present as homonymous visual field deficits. Recent evidence suggests that visual training in the blind field can partially reverse blindness at trained locations. However, the efficacy of visual training to improve vision is highly variable across subjects, and the reasons for this are poorly understood. It is likely that variance in residual functional or structural neural circuitry following the insult may underlie the variation among patients. Many patients with visual field deficits retain residual visual processing in their blind field, termed 'blindsight', despite a lack of awareness. Previous research indicates that an intact structural and functional connection between the dorsal lateral geniculate nucleus (dLGN) and the human extrastriate visual motion-processing area (hMT+) is necessary for blindsight to occur. We therefore predict that changes in this white matter pathway will underlie improvements in motion discrimination training. Twenty stroke survivors with unilateral, homonymous field defects from retro-geniculate brain lesions will complete 6 months of motion discrimination training at home. Visual training will involve performing two daily sessions of a motion discrimination task, at two non-overlapping locations in the blind field, at least 5 days per week. Motion discrimination and integration thresholds, Humphrey perimetry and structural and diffusion-weighted MRI will be collected pre- and post-training. Changes in fractional anisotropy will be analysed in two visual tracts: (i) between the ipsilesional dLGN and hMT+ and (ii) between the ipsilesional dLGN and V1. The (non-visual) tract between the ventral posterior lateral nucleus of the thalamus (VPL) and the primary somatosensory cortex (S1) will be analysed as a control. Tractographic changes will be compared to improvements in motion discrimination and Humphrey perimetry-derived metrics. We predict that (i) improved motion discrimination performance will be directly related to increased fractional anisotropy in the pathway between ipsilesional dLGN and hMT+ and (ii) improvements in Humphrey perimetry will be related to increased fractional anisotropy in the dLGN-V1 pathway. There should be no relationship between behavioural measures and changes in fractional anisotropy in the VPL-S1 pathway. This study has the potential to lead to greater understanding of the white matter microstructure of pathways underlying the behavioural outcomes resulting from visual training in retro-geniculate strokes. Understanding the neural mechanisms that underlie visual rehabilitation is fundamental to the development of more targeted and thus effective treatments for this underserved patient population.

After a first epileptic seizure, anti-seizure medications (ASMs) can change the likelihood of having a further event. This prospective study aimed to quantify brain network changes associated with taking ASM monotherapy. We applied graph theoretical network analysis to longitudinal resting-state functional MRI (fMRI) data from 28 participants who had recently experienced their first seizure. Participants were imaged before and during long-term ASM therapy, with a mean inter-scan interval of 6.9 months. After commencing ASM, we observed an increase in the clustering coefficient and a decrease in network path length. Brain changes after ASM treatment were most prominent in the superior frontoparietal and inferior fronto-temporal regions. Participants with recurrent seizures display the most pronounced network changes after ASM treatment. This study shows changes in brain network function after ASM administration, particularly in participants with recurrent seizures. Larger studies that ideally include control cohorts are required to understand further the connection between ASM-related brain network changes and longer-term seizure status.

Alcohol use disorder is a chronic disease characterized by an inappropriate pattern of drinking, resulting in negative consequences for the individual's physical, mental and social health. Korsakoff's syndrome is a complication of alcohol use disorder and is characterized by severe memory and executive deficits. The fronto-cerebellar and Papez circuits are structurally affected in patients with alcohol use disorder with and without Korsakoff's syndrome. The first objective of the present study was to measure the effect of chronic and excessive alcohol consumption on resting-state functional connectivity of these two functional brain networks. The second objective was to identify, for the first time, resting-state functional connectivity abnormalities specific to amnesic patients with Korsakoff's syndrome. In the present study, a neuropsychological assessment and a resting-state functional magnetic resonance imaging examination were conducted in 31 healthy controls (43.6 ± 6.1 years) and 46 patients (46.6 ± 9.1 years) with alcohol use disorder including 14 patients with Korsakoff's syndrome (55.5 ± 5.3 years) to examine the effect of chronic and heavy alcohol consumption on functional connectivity of the fronto-cerebellar and the Papez circuits at rest and the specificity of functional connectivity changes in Korsakoff's syndrome compared to alcohol use disorder without Korsakoff's syndrome. The resting-state functional connectivity analyses focused on the nodes of the fronto-cerebellar and Papez circuits and combined region of interest and graph theory approaches, and whether these alterations are associated with the neuropsychological profile. In patients pooled together compared to controls, lower global efficiency was observed in the fronto-cerebellar circuit. In addition, certain regions of the fronto-cerebellar and Papez circuits were functionally hyperconnected at rest, which positively correlated with executive functions. Patients with Korsakoff's syndrome showed lower resting-state functional connectivity, lower local and global efficiency within the Papez circuit compared to those without Korsakoff's syndrome. Resting-state functional connectivity positively correlated with several cognitive scores in patients with Korsakoff's syndrome. The fronto-cerebellar and Papez circuits, two normally well-segregated networks, are functionally altered by alcohol use disorder. The Papez circuit attempts to compensate for deficits in the fronto-cerebellar circuit, albeit insufficiently as evidenced by patients' overall lower cognitive performance. Korsakoff's syndrome is characterized by altered functional connectivity in the Papez circuit known to be centrally involved in memory.

Rasmussen's encephalitis is a rare, progressive neurological inflammatory with hemispheric brain atrophy. Epilepsy partialis continua (EPC) is a diagnostic clinical condition in patients with Rasmussen's encephalitis. However, the incidence of EPC in the natural course of Rasmussen's encephalitis is only about 50%. The majority of experts hold the belief that EPC is associated with dysfunction in the motor cortex, yet the whole pathogenesis remains unclear. We hypothesize that there is a characteristic topological discrepancy between groups with EPC and without EPC from the perspective of structural connectome. To this end, we described the structural MRI findings of 20 Rasmussen's encephalitis cases, 11 of which had EPC, and 9 of which did not have EPC (NEPC), and 20 healthy controls. We performed voxel-based morphometry to evaluate the alterations of grey matter volume. Using a volume-based structural covariant network, the hub distribution and modularity were studied at the group level. Based on the radiomic features, an individual radiomics structural similarity network was constructed for global topological properties, such as small-world index, higher path length, and clustering coefficient. And then, the Pearson correlation was used to delineate the association between duration and topology properties. In the both EPC and NEPC groups, the volume of the motor cortex on the affected side was significantly decreased, but putamen atrophy was most pronounced in the EPC group. Hubs in the EPC group consisted of the executive network, and the contralateral putamen was the hub in the NEPC group with the highest betweenness centrality. Compared to the NEPC, the EPC showed a higher path length and clustering coefficient in the structural similarity network. Moreover, the function of morphological network integration in EPC patients was diminished as the duration of Rasmussen's encephalitis increased. Our study indicates that motor cortex atrophy may not be directly related to EPC patients. Whereas atrophy of the putamen, and a more regularized configuration may contribute to the generation of EPC. The findings further suggest that the putamen could potentially serve as a viable target for controlling EPC in patients with Rasmussen's encephalitis.

This scientific commentary refers to 'Patterns of cortical thickness alterations in degenerative cervical myelopathy: associations with dexterity and gait dysfunctions', by Muhammad et al. (https://doi.org/10.1093/braincomms/fcae279).

Creating a mouse model that recapitulates human tau pathology is essential for developing strategies to intervene in tau-induced neurodegeneration. However, mimicking the pathological features seen in human pathology often involves a trade-off with artificial effects such as unexpected gene insertion and neurotoxicity from the expression system. To overcome these issues, we developed the rTKhomo mouse model by combining a transgenic CaMKII-tTA system with a P301L mutated 1N4R human tau knock-in at the Rosa26 locus with a C57BL/6J background. This model closely mimics human tau pathology, particularly in the hippocampal CA1 region, showing age-dependent tau accumulation, neuronal loss and neuroinflammation. Notably, whole-brain 3D staining and light-sheet microscopy revealed a spatial gradient of tau deposition from the entorhinal cortex to the hippocampus, similar to the spatial distribution of Braak neurofibrillary tangle staging. Furthermore, [¹⁸F]PM-PBB3 positron emission tomography imaging enabled the quantification and live monitoring of tau deposition. The rTKhomo mouse model shows potential as a promising next-generation preclinical tool for exploring the mechanisms of tauopathy and for developing interventions targeting the spatial progression of tau pathology.

Age-related differences in cortical microstructure are used to understand the neuronal mechanisms that underlie human brain ageing. The cerebral vasculature contributes to cortical ageing, but its precise interaction with cortical microstructure is poorly understood. In a cross-sectional study, we combine venous imaging with vessel distance mapping to investigate the interaction between venous distances and age-related differences in the microstructural architecture of the primary somatosensory cortex, the primary motor cortex and additional areas in the frontal cortex as non-sensorimotor control regions. We scanned 18 younger adults and 17 older adults using 7 Tesla MRI to measure age-related changes in longitudinal relaxation time (T1) and quantitative susceptibility mapping (QSM) values at 0.5 mm isotropic resolution. We modelled different cortical depths using an equi-volume approach and assessed the distance of each voxel to its nearest vein using vessel distance mapping. Our data reveal a dependence of cortical quantitative T1 values and positive QSM values on venous distance. In addition, there is an interaction between venous distance and age on quantitative T1 values, driven by lower quantitative T1 values in older compared to younger adults in voxels that are closer to a vein. Together, our data show that the local venous architecture explains a significant amount of variance in standard measures of cortical microstructure and should be considered in neurobiological models of human brain organisation and cortical ageing.

Sudden sensorineural hearing loss, a prevalent emergency in otolaryngology, is known to potentially precipitate cognitive and emotional disorders in affected individuals. Extensive research has documented the phenomenon of cortical functional reorganization in patients with sudden sensorineural hearing loss. However, the potential link between this neural functional remodelling and cognitive-emotional disorders remains unclear. To investigate this issue, 30 bilateral sudden sensorineural hearing loss patients and 30 healthy adults were recruited for this study. We collected clinical data and resting-state functional magnetic resonance imaging data from the participants. Gradient mapping analysis was employed to calculate the first three gradients for each subject. Subsequently, gradient changes in sudden sensorineural hearing loss patients were compared with healthy controls at global, regional and network levels. Finally, we explored the relationship between gradient values and clinical variables. The results revealed that at the global level, sudden sensorineural hearing loss did not exhibit significant differences in the primary gradient but showed a state of compression in the second and third gradients. At the regional level, sudden sensorineural hearing loss patients exhibited a significant reduction in the primary gradient values in the temporal pole and ventral prefrontal cortex, which were closely related to neuro-scale scores. Regarding the network level, sudden sensorineural hearing loss did not show significant differences in the primary gradient but instead displayed significant changes in the control network and default mode network in the second and third gradients. This study revealed disruptions in the functional hierarchy of sudden sensorineural hearing loss, and the alterations in functional connectivity gradients were closely associated with cognitive and emotional disturbances in patients. These findings provide new evidence for understanding the functional remodelling that occurs in sudden sensorineural hearing loss.

Epilepsy and Alzheimer's disease share some common pathologies such as neurodegeneration, seizures and impaired cognition. However, the molecular mechanisms of these changes are still largely unknown. Fyn, a Src-family non-receptor tyrosine kinase (SFK), and its interaction with tau in mediating brain pathology in epilepsy and Alzheimer's disease can be a potential therapeutic target for disease modification. Although Fyn and tau pathology occurs in both Alzheimer's disease and epilepsy, the dynamics of Fyn-tau and PSD95-NR2B interactions affected by seizures and their impact on brain pathology in epilepsy have not been investigated. In this study, we demonstrate a significant increase of Fyn-tau interactions following seizure induction by kainate in both acute and chronic rodent models and in human epilepsy. In the early phase of epileptogenesis, we show increased Fyn/tau/NR2B/PSD95/neuronal nitric oxide synthase complexes after status epilepticus and a postsynaptic increase of phosphorylated tau (pY18 and AT8), Fyn (pSFK-Y416), NMDAR (pNR2B-Y1472) and neuronal nitric oxide synthase. Hippocampal proximity ligation assay and co-immunoprecipitation revealed a sustained increase of Fyn-tau and NR2B-PSD95 complexes/binding in rat chronic epilepsy at 3 months post-status epilepticus. Enhanced Fyn-tau complexes strongly correlated with the frequency of spontaneously recurring convulsive seizures and epileptiform spikes in the chronic epilepsy model. In human epileptic brains, we also identified increased Fyn-tau and NR2B-PSD95 complexes, tau phosphorylation (pY18 and AT8) and Fyn activation (pSFK-Y416), implying the translational and therapeutic potential of these molecular interactions. In tau knockout mice and in rats treated with a Fyn/SFK inhibitor saracatinib, we found a significant reduction of phosphorylated Fyn, tau (AT8 in saracatinib-treated), NR2B and neuronal nitric oxide synthase and their interactions (Fyn-tau and NR2B-PSD95 in saracatinib-treated group; NR2B-PSD95 in tau knockout group). The reduction of Fyn-tau and NR2B-PSD95 interactions in the saracatinib-treated group, in contrast to the vehicle-treated group, correlated with the modification in seizure progression in the rat chronic epilepsy model. These findings from animal models and human epilepsy provide evidence for the role of Fyn-tau and NR2B-PSD95 interactions in seizure-induced brain pathology and suggest that blocking such interactions could modify the progression of epilepsy.