Tau propagation in the brain olfactory circuits is associated with smell perception changes in aging.

The direct access of olfactory afferents to memory-related cortical systems has inspired theories about the role of the olfactory pathways in the development of cortical neurodegeneration in Alzheimer's disease (AD). In this study, we used baseline olfactory identification measures with longitudinal flortaucipir and PiB PET, diffusion MRI of 89 cognitively normal older adults (73.82 ± 8.44 years; 56% females), and a transcriptomic data atlas to investigate the spatiotemporal spreading and genetic vulnerabilities of AD-related pathology aggregates in the olfactory system. We find that odor identification deficits are predominantly associated with tau accumulation in key areas of the olfactory pathway, with a particularly strong predictive power for longitudinal tau progression. We observe that tau spreads from the medial temporal lobe structures toward the olfactory system, not the reverse. Moreover, we observed a genetic background of odor perception-related genes that might confer vulnerability to tau accumulation along the olfactory system.

Divergent connectomic organization delineates genetic evolutionary traits in the human brain.

The relationship between human brain connectomics and genetic evolutionary traits remains elusive due to the inherent challenges in combining complex associations within cerebral tissue. In this study, insights are provided about the relationship between connectomics, gene expression and divergent evolutionary pathways from non-human primates to humans. Using in vivo human brain resting-state data, we detected two co-existing idiosyncratic functional systems: the segregation network, in charge of module specialization, and the integration network, responsible for information flow. Their topology was approximated to whole-brain genetic expression (Allen Human Brain Atlas) and the co-localization patterns yielded that neuron communication functionalities-linked to Neuron Projection-were overrepresented cell traits. Homologue-orthologue comparisons using dN/dS-ratios bridged the gap between neurogenetic outcomes and biological data, summarizing the known evolutionary divergent pathways within the Homo Sapiens lineage. Evidence suggests that a crosstalk between functional specialization and information flow reflects putative biological qualities of brain architecture, such as neurite cellular functions like axonal or dendrite processes, hypothesized to have been selectively conserved in the species through positive selection. These findings expand our understanding of human brain function and unveil aspects of our cognitive trajectory in relation to our simian ancestors previously left unexplored.

Central neurogenetic signatures of the visuomotor integration system.

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.

Distance disintegration delineates the brain connectivity failure of Alzheimer's disease.

Alzheimer's disease (AD) is associated with brain network dysfunction. Network-based investigations of brain connectivity have mainly focused on alterations in the strength of connectivity; however, the network breakdown in AD spectrum is a complex scenario in which multiple pathways of connectivity are affected. To integrate connectivity changes that occur under AD-related conditions, here we developed a novel metric that computes the connectivity distance between cortical regions at the voxel level (or nodes). We studied 114 individuals with mild cognitive impairment, 24 with AD, and 27 healthy controls. Results showed that areas of the default mode network, salience network, and frontoparietal network display a remarkable network separation, or greater connectivity distances, from the rest of the brain. Furthermore, this greater connectivity distance was associated with lower global cognition. Overall, the investigation of AD-related changes in paths and distances of connectivity provides a novel framework for characterizing subjects with cognitive impairment; a framework that integrates the overall network topology changes of the brain and avoids biases toward unreferenced connectivity effects.

Neurofilament-lysosomal genetic intersections in the cortical network of stuttering.

The neurobiological underpinnings of stuttering, a speech disorder characterized by disrupted speech fluency, remain unclear. While recent developments in the field have afforded researchers the ability to pinpoint several genetic profiles associated with stuttering, how these specific genetic backgrounds impact neuronal circuits and how they generate or facilitate the emergence of stuttered speech remains unknown. In this study, we identified the large-scale cortical network that characterizes stuttering using functional connectivity MRI and graph theory. We performed a spatial similarity analysis that examines whether the topology of the stuttering cortical network intersects with genetic expression levels of previously reported genes for stuttering from the protein-coding transcriptome data of the Allen Human Brain Atlas. We found that GNPTG - a gene involved in the mannose-6-phosphate lysosomal targeting pathways - was significantly co-localized with the stuttering cortical network. An enrichment analysis demonstrated that the genes identified with the stuttering cortical network shared a significantly overrepresented biological functionality of Neurofilament Cytoskeleton Organization (NEFH, NEFL and INA). The relationship between lysosomal pathways, cytoskeleton organization, and stuttering, was investigated by comparing the genetic interactome between GNPTG and the neurofilament genes implicated in the current study. We found that genes of the interactome network, including CDK5, SNCA, and ACTB, act as functional links between lysosomal and neurofilament genes. These findings support the notion that stuttering is due to a lysosomal dysfunction, which has deleterious effects on the neurofilament organization of the speech neuronal circuits. They help to elucidate the intriguing, unsolved link between lysosomal mutations and the presence of stuttering.

A N400 ERP Study in letter recognition after passive tactile stimulation training in blind children and sighted controls.

BACKGROUND: We previously demonstrated that using a sensory substitution device (SSD) for one week, tactile stimulation results in faster activation of lateral occipital complex in blind children than in seeing controls. OBJECTIVE: We used long-term haptic tactile stimulation training with an SSD to test if it results in stable cross-modal reassignment of visual pathways after six months, to provide high level processing of tactile semantic content. METHODS: We enrolled 12 blind and 12 sighted children. The SSD transforms images to a stimulation matrix in contact with the dominant hand. Subjects underwent twice-daily training sessions, 5 days/week for six months. Children were asked to describe line orientation, name letters, and read words. ERP sessions were performed at baseline and 6 months to analyze the N400 ERP component and reaction times (RT). N400 sources were estimated with Low Resolution Electromagnetic Tomography (LORETA). SPM8 was used to make population-level inferences. RESULTS: We found no group differences in RTs, accuracy of identifications, N400 latencies or distributions with the line task at 1 week or at 6 months. RTs on the letter recognition task were also similar. After 6 months, behavioral training increased accurate letter identification in both seeing and blind children (Chi 2 = 11906.934, p = 0.000), but the increase was larger in blind children (Chi 2 = 8.272, p = 0.004). Behavioral training shifted peak N400 amplitude to left occipital and bilateral parietal cortices in blind children, but to left precentral and postcentral and bilateral occipital cortices in sighted controls. CONCLUSIONS: Blind children learn to recognize SSD-delivered letters better than seeing controls and had greater N400 amplitude in the occipital region. To the best of our knowledge, our results provide the first published example of standard letter recognition (not Braille) by children with blindness using a tactile delivery system.

Multi-Modal Signatures of Tau Pathology, Neuronal Fiber Integrity, and Functional Connectivity in Traumatic Brain Injury.

[18F]AV-1451 (aka 18F-Flortaucipir, [18F]T807) was developed for positron-emission tomography (PET) imaging of paired helical filaments of hyperphosphorylated tau, which are of interest in a range of neuropathologies, including traumatic brain injury (TBI). Magnetic resonance imaging (MRI) techniques like diffusion tensor imaging (DTI) and resting state functional connectivity assess structural and functional characteristics of the brain, complementing the molecular information that can be obtained by PET. The goal herein was to explore the utility of such multi-modal imaging in a case series based on a population of TBI subjects. This study probes the interrelationship between tau deposition, white matter integrity, and gray matter functional connectivity across the spectrum of TBI. Nineteen subjects (11 controls, five former contact sports athletes, one automotive accident, and two with military-related injury) underwent [18F]AV-1451 PET and magnetic resonance scanning procedures. [18F]AV-1451 distribution volume ratio (DVR) was estimated using the Logan method and the cerebellum as a reference region. Diffusion tractography images and fractional anisotropy (FA) images were generated using diffusion toolkit and FSL. Resting-state functional MRI (fMRI) analysis was based on a graph theory metric, namely weighted degree centrality. TBI subjects showed greater heterogeneity in [18F]AV-1451 DVR when compared with control subjects. In a subset of TBI subjects, areas with high [18F]AV-1451 binding corresponded with increased FA and diminished white matter tract density in DTI. Functional MRI results exhibited an increase in functional connectivity, particularly among local connections, in the areas where tau aggregates were more prevalent. In a case series of a diverse group of TBI subjects, brain regions with elevated tau burden exhibited increased functional connectivity as well as decreased white matter integrity. These findings portray molecular, microstructural, and functional corollaries of TBI that spatially coincide and can be measured in the living human brain using noninvasive neuroimaging techniques.

Corticolimbic fast-tracking: enhanced multimodal integration in functional neurological disorder.

OBJECTIVE: Some 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. METHODS: Between-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. RESULTS: Compared 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. CONCLUSIONS: These neuroimaging findings suggest potential candidate neurocircuit pathways in the pathophysiology of FND.

Sequence Alterations of Cortical Genes Linked to Individual Connectivity of the Human Brain.

Individual differences in humans are driven by unique brain structural and functional profiles, presumably mediated in part through differential cortical gene expression. However, the relationships between cortical gene expression profiles and individual differences in large-scale neural network organization remain poorly understood. In this study, we aimed to investigate whether the magnitude of sequence alterations in regional cortical genes mapped onto brain areas with high degree of functional connectivity variability across individuals. First, human genetic expression data from the Allen Brain Atlas was used to identify protein-coding genes associated with cortical areas, which delineated the regional genetic signature of specific cortical areas based on sequence alteration profiles. Thereafter, we identified brain regions that manifested high degrees of individual variability by using test-retest functional connectivity magnetic resonance imaging and graph-theory analyses in healthy subjects. We found that rates of genetic sequence alterations shared a distinct spatial topography with cortical regions exhibiting individualized (highly-variable) connectivity profiles. Interestingly, gene expression profiles of brain regions with highly individualized connectivity patterns and elevated number of sequence alterations are devoted to neuropeptide-signaling-pathways and chemical-synaptic-transmission. Our findings support that genetic sequence alterations may underlie important aspects of brain connectome individualities in humans. Significance Statement: The neurobiological underpinnings of our individuality as humans are still an unsolved question. Although the notion that genetic variation drives an individual's brain organization has been previously postulated, specific links between neural connectivity and gene expression profiles have remained elusive. In this study, we identified the magnitude of population-based sequence alterations in discrete cortical regions and compared them to the brain topological distribution of functional connectivity variability across an independent human sample. We discovered that brain regions with high degree of connectional individuality are defined by increased rates of genetic sequence alterations; these findings specifically implicated genes involved in neuropeptide-signaling pathways and chemical-synaptic transmission. These observations support that genetic sequence alterations may underlie important aspects of the emergence of the brain individuality across humans.

Neurogenetic contributions to amyloid beta and tau spreading in the human cortex.

Tau and amyloid beta (Aß) proteins accumulate along neuronal circuits in Alzheimer's disease. 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 Aß and tau positron emission tomography imaging of healthy adult individuals and the genetic transcriptome of the Allen Human Brain Atlas. We identified distinctive pathways for tau and Aß accumulation, of which the tau pathways correlated with cognitive levels. We found that tau propagation and Aß 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 Aß profile as 'dendrite related'. This study reveals distinct genetic profiles that may confer vulnerability to tau and Aß in vivo propagation in the human brain.

Positive Connectivity Predicts the Dynamic Intrinsic Topology of the Human Brain Network.

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.

[Association of health-related quality of life and suicidal risk in adolescents: A cross-sectional study]. / Asociación entre la calidad de vida relacionada con la salud y riesgo suicida en adolescentes: estudio transversal.

INTRODUCTION: Health-related quality of life (HRQoL) deterioraton is a risk factor for suicide in adults, however, this aspect has been little studied in adolescents. OBJECTIVE: To evaluate the asso ciation between HRQoL (measured with EQ-5D-5L) and suicidal risk in adolescents and its capacity for cross-sectional detection of suicidal risk. PATIENTS AND METHOD: 128 adolescents (15-19 years old) from Puerto Aysen (Chile) responded to the EQ-5D-5L questionnaire, the Okasha Suicide Scale and two anchoring questions of imminent suicide risk. A suicide risk case was considered to have a > 5 score on the Okasha scale or the affirmative answer to one of the anchoring questions. The index value of EQ-5D-5L was calculated and Odds Ratios (ORs) were estimated with confidence intervals (95% CI), adjusted for confounders. Areas under the ROC curve (AUC-ROC) were calculated to assess the discriminatory performance of EQ-5D-5L. RESULTS: 21 (16.4%) adolescents were at suicidal risk. Controlling for confounders, the EQ-5D-5L dimensions associated with suicidal risk were pain/ discomfort (OR: 2.5; 95% CI 1.1-6.1) and anxiety/depression (OR: 2.2; 95% CI 1.3-3.6). The AUC- ROC for both dimensions was 85% (95% CI 0.75-0.91) and 81% for the EQ-5D-5L index value (95% CI 0.72-0.89). CONCLUSIONS: HRQoL could be a risk factor for suicide in adolescents and in this way, the EQ-5D-5L could help in searching for high risk and hidden cases of suicidal risk.

Asociación entre la calidad de vida relacionada con la salud y riesgo suicida en adolescentes: estudio transversal / Association of health-related quality of life and suicidal risk in adolescents: a cross-sectional study

INTRODUCCIÓN: El deterioro de la calidad de vida relacionada con la salud (CVRS) es un factor de riesgo de suicido en adultos; no obstante, poco se ha estudiado esta dimensión en adolescentes. OBJETIVO: Evaluar la asociación entre calidad de vida relacionada con la salud, medido con el EQ-5D-5L, y riesgo suicida en adolescentes y su capacidad de detección transversal de riesgo suicida. PACIENTES Y MÉTODO: 128 jóvenes (15-19 años) de la comuna de Puerto Aysén (Chile) respondieron transversalmente el EQ-5D-5L, la escala de suicidalidad de Okasha y dos preguntas de anclaje de riesgo in minente de suicidio. Se consideró como caso de riesgo suicida a un puntaje > 5 en la escala Okasha o la respuesta afirmativa a una de las preguntas de anclaje. Se calculó el valor índice con los perfiles de salud del EQ-5D-5L. Se estimaron Odds Ratios (OR's) con intervalos de confianza (IC95%), ajustando por confusores y se calcularon áreas bajo la curva ROC (AUC-ROC) para evaluar la capacidad de pesquisa del EQ-5D-5L. RESULTADOS: 21 (16,4%) adolescentes fueron considerados como casos de riesgo suicida. Controlando por confusores, las dimensiones del EQ-5D-5L que se asociaron con riesgo suicida fueron: dolor/malestar (OR: 2,5; IC95% 1,1-6,1) y ansiedad/depresión (OR: 2,2; IC95% 1,3-3,6). El AUR-ROC para ambas dimensiones fue del 0,85% (IC95% 0,75-0,91) y de 0,81% para el valor del índice del EQ-5D-5L (IC95% 0,72-0,89). CONCLUSIONES: La CVRS podría ser un factor de riesgo de suicidio en adolescentes; y el EQ-5D-5L que mide esta dimensión, podría ayudar a pesquisar futuros casos y casos ocultos de riesgo suicida.

INTRODUCTION: Health-related quality of life (HRQoL) deterioraton is a risk factor for suicide in adults, however, this aspect has been little studied in adolescents. OBJECTIVE: To evaluate the asso ciation between HRQoL (measured with EQ-5D-5L) and suicidal risk in adolescents and its capacity for cross-sectional detection of suicidal risk. PATIENTS AND METHOD: 128 adolescents (15-19 years old) from Puerto Aysen (Chile) responded to the EQ-5D-5L questionnaire, the Okasha Suicide Scale and two anchoring questions of imminent suicide risk. A suicide risk case was considered to have a > 5 score on the Okasha scale or the affirmative answer to one of the anchoring questions. The index value of EQ-5D-5L was calculated and Odds Ratios (ORs) were estimated with confidence intervals (95% CI), adjusted for confounders. Areas under the ROC curve (AUC-ROC) were calculated to assess the discriminatory performance of EQ-5D-5L. RESULTS: 21 (16.4%) adolescents were at suicidal risk. Controlling for confounders, the EQ-5D-5L dimensions associated with suicidal risk were pain/ discomfort (OR: 2.5; 95% CI 1.1-6.1) and anxiety/depression (OR: 2.2; 95% CI 1.3-3.6). The AUC- ROC for both dimensions was 85% (95% CI 0.75-0.91) and 81% for the EQ-5D-5L index value (95% CI 0.72-0.89). CONCLUSIONS: HRQoL could be a risk factor for suicide in adolescents and in this way, the EQ-5D-5L could help in searching for high risk and hidden cases of suicidal risk.

[RADAR: a program for the prevention of suicide in adolescents in the region of Aysen, Chile, preliminary results]. / El programa RADAR para la prevención del suicidio en adolescentes de la región de Aysén, Chile: resultados preliminares.

OBJECTIVE: We present the preliminary results of the implementation of RADAR: a community suicide prevention program in adolescents implemented in two high schools in a south region of Chile. METHOD: In a pilot study, during 2016, we implemented RADAR in two high schools of Puerto Aysen, in in the Region of Aysen of Chile. A total of 409 actors were trained (among students, school teachers, caregivers and health professionals) for the screening and referral of high suicide risk adolescents. RESULTS: Out of a total of 144 students who passed the RADAR screening systems, 29 cases were detected as suicide risk (20%) and 27 of them were opportunely referred to the Emergency Service of the Hospital of Puerto Aysen. In the second RADAR screening campaign, 3 months later, 90% of the cases no longer presented suicide risk. CONCLUSION: These results show the high proportion of ado lescents at risk of suicide who are not visible by the health system and the feasibility of implementing RADAR in the community as an effective suicide prevention intervention.

El programa RADAR para la prevención del suicidio en adolescentes de la región de Aysén, Chile: resultados preliminares / RADAR: a program for the prevention of suicide in adolescents in the region of Aysen, Chile, preliminary results

OBJETIVO: Dar a conocer los resultados preliminares del programa comunitario RADAR (Red para la Atención y Derivación de Adolescentes en Riesgo suicida). MÉTODO: Durante el 2016, RADAR fue implementado como prueba de concepto en dos colegios de Puerto Aysén de la Región de Aysén, Chile. Se capacitó un total de 409 participantes (entre alumnos, profesores de los colegios, apoderados y profesionales de la salud) para la pesquisa y derivación de adolescentes en riego de suicidio. RESULTADOS: De un total de 144 alumnos que pasaron los sistemas de pesquisa de RADAR, se detectaron 29 casos en riesgo suicida (20%) y 27 fueron derivados oportunamente al Servicio de Urgencia del Hos pital de Puerto Aysén. En la segunda campaña de pesquisa de RADAR, 3 meses después, el 90% de los casos ya no presentaba riesgo suicida. CONCLUSIÓN: Estos resultados muestran la alta proporción de adolescentes en riesgo suicida que no son visibilizados por el sistema de salud y la factibilidad de implementar RADAR en la comunidad como una intervención preventiva efectiva.

OBJECTIVE: We present the preliminary results of the implementation of RADAR: a community suicide prevention program in adolescents implemented in two high schools in a south region of Chile. METHOD: In a pilot study, during 2016, we implemented RADAR in two high schools of Puerto Aysen, in in the Region of Aysen of Chile. A total of 409 actors were trained (among students, school teachers, caregivers and health professionals) for the screening and referral of high suicide risk adolescents. RESULTS: Out of a total of 144 students who passed the RADAR screening systems, 29 cases were detected as suicide risk (20%) and 27 of them were opportunely referred to the Emergency Service of the Hospital of Puerto Aysen. In the second RADAR screening campaign, 3 months later, 90% of the cases no longer presented suicide risk. CONCLUSION: These results show the high proportion of ado lescents at risk of suicide who are not visible by the health system and the feasibility of implementing RADAR in the community as an effective suicide prevention intervention.

Brain circuit-gene expression relationships and neuroplasticity of multisensory cortices in blind children.

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.

Epicenters of dynamic connectivity in the adaptation of the ventral visual system.

OBJECTIVES AND DESIGN: Neuronal responses adapt to familiar and repeated sensory stimuli. Enhanced synchrony across wide brain systems has been postulated as a potential mechanism for this adaptation phenomenon. Here, we used recently developed graph theory methods to investigate hidden connectivity features of dynamic synchrony changes during a visual repetition paradigm. Particularly, we focused on strength connectivity changes occurring at local and distant brain neighborhoods. PRINCIPAL OBSERVATIONS: We found that connectivity reorganization in visual modal cortex-such as local suppressed connectivity in primary visual areas and distant suppressed connectivity in fusiform areas-is accompanied by enhanced local and distant connectivity in higher cognitive processing areas in multimodal and association cortex. Moreover, we found a shift of the dynamic functional connections from primary-visual-fusiform to primary-multimodal/association cortex. CONCLUSIONS: These findings suggest that repetition-suppression is made possible by reorganization of functional connectivity that enables communication between low- and high-order areas. Hum Brain Mapp 38:1965-1976, 2017. © 2017 Wiley Periodicals, Inc.

Brain Plasticity in Blind Subjects Centralizes Beyond the Modal Cortices.

It is well established that the human brain reorganizes following sensory deprivations. In blind individuals, visual processing regions including the lateral occipital cortex (LOC) are activated by auditory and tactile stimuli as demonstrated by neurophysiological and neuroimaging investigations. The mechanisms for such plasticity remain unclear, but shifts in connectivity across existing neural networks appear to play a critical role. The majority of research efforts to date have focused on neuroplastic changes within visual unimodal regions, however we hypothesized that neuroplastic alterations may also occur in brain networks beyond the visual cortices including involvement of multimodal integration regions and heteromodal cortices. In this study, two recently developed graph-theory based functional connectivity analyses, interconnector analyses and local and distant connectivity, were applied to investigate functional reorganization in regional and distributed neural-systems in late-onset blind (LB) and congenitally blind (CB) cohorts each compared to their own group of sighted controls. While functional network alterations as measured by the degree of differential links (DDL) occurred in sensory cortices, neuroplastic changes were most prominent within multimodal and association cortices. Subjects with LB showed enhanced multimodal integration connections in the parieto-opercular, temporoparietal junction (TPJ) and ventral premotor (vPM) regions, while CB individuals exhibited increased superior parietal cortex (SPC) connections. This study reveals the critical role of recipient multi-sensory integration areas in network reorganization and cross-modal plasticity in blind individuals. These findings suggest that aspects of cross-modal neuroplasticity and adaptive sensory-motor and auditory functions may potentially occur through reorganization in multimodal integration regions.

Differences in Early Stages of Tactile ERP Temporal Sequence (P100) in Cortical Organization during Passive Tactile Stimulation in Children with Blindness and Controls.

Compared to their seeing counterparts, people with blindness have a greater tactile capacity. Differences in the physiology of object recognition between people with blindness and seeing people have been well documented, but not when tactile stimuli require semantic processing. We used a passive vibrotactile device to focus on the differences in spatial brain processing evaluated with event related potentials (ERP) in children with blindness (n = 12) vs. normally seeing children (n = 12), when learning a simple spatial task (lines with different orientations) or a task involving recognition of letters, to describe the early stages of its temporal sequence (from 80 to 220 msec) and to search for evidence of multi-modal cortical organization. We analysed the P100 of the ERP. Children with blindness showed earlier latencies for cognitive (perceptual) event related potentials, shorter reaction times, and (paradoxically) worse ability to identify the spatial direction of the stimulus. On the other hand, they are equally proficient in recognizing stimuli with semantic content (letters). The last observation is consistent with the role of P100 on somatosensory-based recognition of complex forms. The cortical differences between seeing control and blind groups, during spatial tactile discrimination, are associated with activation in visual pathway (occipital) and task-related association (temporal and frontal) areas. The present results show that early processing of tactile stimulation conveying cross modal information differs in children with blindness or with normal vision.

Occipital cortex activation by long-term repetitive tactile stimulation is necessary for object recognition in blinds: a case report.

Tactile vision has been approached from a variety of angles using different techniques. So far, a certain kind of object (and text) recognition has been shown, though seeing as such has not been achieved yet, and it remains unclear. Trough repetitive passive tactile stimulation perceptual processing is transferred from temporo-parietal to occipital areas, which affects object recognition. We report the results of passive tactile stimulation, as well as rTMS, applied to a 50 year old left handed blind male with over 97% loss of vision, who suffers from Peter's anomaly and microphthalmia. After 15 weeks of passive tactile stimulation, the subject showed increased activity in occipital areas associated with the development of visual-like perception which remained unchanged after three months without passive tactile stimulation. Inhibitory rTMS over the visual cortex led to noticeable reduction of spatial recognition performance and visual sensations in this subject. Stable changes in occipital cortical activity can be associated with subjective sensations of seeing. Once occipital activation has been achieved, it is necessary for spatial object recognition. Both facts highlight the implication of occipital areas in tactile vision and the cortical plasticity of passive tactile long-term stimulation in people with blindness.