Tau and beta-amyloid (Aβ) proteins accumulate along neuronal circuits in Alzheimer’s disease (AD). Unraveling the genetic background for the regional vulnerability of these proteinopathies can help in understanding the mechanisms of pathology progression. To that end, we developed a novel graph theory approach and used it to investigate the intersection of longitudinal Aβ and tau PET imaging of healthy adult individuals and the genetic transcriptome of the Allen Human Brain Atlas. We identified distinctive pathways for tau and Aβ accumulation, of which the tau pathways correlated with cognitive levels. We found that tau- and Aβ-propagation patterns were associated with a common genetic profile related to lipid metabolism, in which APOE played a central role, whereas the tau-specific genetic profile was classified as “axon-related” and the Aβ profile as “dendrite-related”. This is the first study revealing distinct genetic profiles that may confer vulnerability to tau- and Aβ-in-vivo-propagation in the human brain.

Over three months of intensive training with a tactile stimulation device, 18 blind and 10 blindfolded seeing subjects improved in their ability to identify geometric figures by touch. Seven blind subjects spontaneously reported ‘visual qualia’, the subjective sensation of seeing flashes of light congruent with tactile stimuli. In the latter subjects tactile stimulation evoked activation of occipital cortex on electroencephalography (EEG). None of the blind subjects who failed to experience visual qualia, despite identical tactile stimulation training, showed EEG recruitment of occipital cortex. None of the blindfolded seeing humans reported visual-like sensations during tactile stimulation. These findings support the notion that the conscious experience of seeing is linked to the activation of occipital brain regions in people with blindness. Moreover, the findings indicate that provision of visual information can be achieved through non-visual sensory modalities which may help to minimize the disability of blind individuals, affording them some degree of object recognition and navigation aid.

ObjectiveSome individuals with functional neurological disorder (FND) exhibit motor and affective disturbances, along with limbic hyper-reactivity and enhanced motor-limbic connectivity. Given that the multimodal integration network (insula, dorsal cingulate, temporoparietal junction (TPJ)) is implicated in convergent sensorimotor, affective and interoceptive processing, we hypothesised that patients with FND would exhibit altered motor and amygdalar resting-state propagation to this network. Patient-reported symptom severity and clinical outcome were also hypothesised to map onto multimodal integration areas.MethodsBetween-group differences in primary motor and amygdalar nuclei (laterobasal, centromedial) were examined using graph-theory stepwise functional connectivity (SFC) in 30 patients with motor FND compared with 30 healthy controls. Within-group analyses correlated functional propagation profiles with symptom severity and prospectively collected 6-month outcomes as measured by the Screening for Somatoform Symptoms Conversion Disorder subscale and Patient Health Questionnaire-15 composite score. Findings were clusterwise corrected for multiple comparisons.ResultsCompared with controls, patients with FND exhibited increased SFC from motor regions to the bilateral posterior insula, TPJ, middle cingulate cortex and putamen. From the right laterobasal amygdala, the FND cohort showed enhanced connectivity to the left anterior insula, periaqueductal grey and hypothalamus among other areas. In within-group analyses, symptom severity correlated with enhanced SFC from the left anterior insula to the right anterior insula and TPJ; increased SFC from the left centromedial amygdala to the right anterior insula correlated with clinical improvement. Within-group associations held controlling for depression, anxiety and antidepressant use.ConclusionsThese neuroimaging findings suggest potential candidate neurocircuit pathways in the pathophysiology of FND.

Highlights We identify the functional connectivity network that characterizes stuttering. We describe the topological similarity of the stuttering cortical network with genetic expression levels from the protein-coding transcriptome data of the Allen Human Brain Atlas. GNPTG significantly co-localizes with the stuttering cortical network. Our findings support that lysosomal-related genes, such as GNPTG, intersect with neurofilament-related genes, which may explain the intriguing link between lysosomal mutations and the presence of stuttering.

Sensory deprivation reorganizes neurocircuits in the human brain. The biological basis of such neuroplastic adaptations remains elusive. In this study, we applied two complementary graph theory-based functional connectivity analyses, one to evaluate whole-brain functional connectivity relationships and the second to specifically delineate distributed network connectivity profiles downstream of primary sensory cortices, to investigate neural reorganization in blind children compared with sighted controls. We also examined the relationship between connectivity changes and neuroplasticity-related gene expression profiles in the cerebral cortex. We observed that multisensory integration areas exhibited enhanced functional connectivity in blind children and that this reorganization was spatially associated with the transcription levels of specific members of the cAMP Response Element Binding protein gene family. Using systems-level analyses, this study advances our understanding of human neuroplasticity and its genetic underpinnings following sensory deprivation.blindness | children | neuroplasticity | functional connectivity | CREB family N europlasticity is an intrinsic ability of the brain to modify and rewire itself following experiences (1). The study of neuroplastic reorganization in blind individuals offers a model through which neuroadaptive processes can be identified. For instance, cross-modal neuroplasticity is a mechanism by which blind individuals recruit visual-related cortices to process sensory information from other perceptual modalities (2-5). In addition to occipital regions, parietal and frontal multimodal integration regions of blind adults are capable of functional connectivity reorganization (6). These brain areas are part of a multimodal integration network that acts as a bridge integrating multisensory functions across cortical regions (7). Our group has previously characterized the hierarchical structure and central position of the multimodal integration network in adult blind subjects (6). Although this finding advances our understanding of how information from primary unimodal cortices is adaptively integrated into higher-order associative areas, it remains unclear if neuroplastic changes within multimodal integration areas also occur in blind children. Furthermore, in addition to clarifying the sites of prominent neuroplastic changes, the biological mechanisms through which neuroplastic alterations occur have yet to be fully elucidated in blind individuals.Concurrent advances in cellular and molecular biology and neuroimaging provide a unique opportunity to explore the interlinked relationships between genes and neural circuits (8). A neuroimaging endophenotype is informative because it is more closely related to the genetic end product than clinical or behavioral phenotypes (9). Thus, examining properties of systemslevel brain organization and cortical gene expression has great potential to expand our understanding of neuroplastic mechanisms, particularly if specific gene expression patt...

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Functional connectivity MRI (fcMRI) has become instrumental in facilitating research of human brain network organization in terms of coincident interactions between positive and negative synchronizations of large-scale neuronal systems. Although there is a common agreement concerning the interpretation of positive couplings between brain areas, a major debate has been made in disentangling the nature of negative connectivity patterns in terms of its emergence in several methodological approaches and its significance/meaning in specific neuropsychiatric diseases. It is still not clear what information the functional negative correlations or connectivity provides or how they relate to the positive connectivity. Through implementing stepwise functional connectivity (SFC) analysis and studying the causality of functional topological patterns, this study aims to shed light on the relationship between positive and negative connectivity in the human brain functional connectome. We found that the strength of negative correlations between voxel-pairs relates to their positive connectivity path-length. More importantly, our study describes how the spatio-temporal patterns of positive connectivity explain the evolving changes of negative connectivity over time, but not the other way around. This finding suggests that positive and negative connectivity do not display equivalent forces but shows that the positive connectivity has a dominant role in the overall human brain functional connectome. This phenomenon provides novel insights about the nature of positive and negative correlations in fcMRI and will potentially help new developments for neuroimaging biomarkers.

Visuomotor impairments characterize numerous neurological disorders and neurogenetic syndromes, such as autism spectrum disorder (ASD) and Dravet, Fragile X, Prader–Willi, Turner, and Williams syndromes. Despite recent advances in systems neuroscience, the biological basis underlying visuomotor functional impairments associated with these clinical conditions is poorly understood. In this study, we used neuroimaging connectomic approaches to map the visuomotor integration (VMI) system in the human brain and investigated the topology approximation of the VMI network to the Allen Human Brain Atlas, a whole-brain transcriptome-wide atlas of cortical genetic expression. We found the genetic expression of four genes—TBR1, SCN1A, MAGEL2, and CACNB4—to be prominently associated with visuomotor integrators in the human cortex. TBR1 gene transcripts, an ASD gene whose expression is related to neural development of the cortex and the hippocampus, showed a central spatial allocation within the VMI system. Our findings delineate gene expression traits underlying the VMI system in the human cortex, where specific genes, such as TBR1, are likely to play a central role in its neuronal organization, as well as on specific phenotypes of neurogenetic syndromes.