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1.
Clin EEG Neurosci ; 53(1): 3-11, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34152841

RESUMO

The abnormal cortices of autism spectrum disorder (ASD) brains are uncertain. However, the pathological alterations of ASD brains are distributed throughout interconnected cortical systems. Functional connections (FCs) methodology identifies cooperation and separation characteristics of information process in macroscopic cortical activity patterns under the context of network neuroscience. Embracing the graph theory concepts, this paper introduces eigenvector centrality index (EC score) ground on the FCs, and further develops a new framework for researching the dysfunctional cortex of ASD in holism significance. The important process is to uncover noticeable regions and subsystems endowed with antagonistic stance in EC-scores of 26 ASD boys and 28 matched healthy controls (HCs). For whole brain regional EC scores of ASD boys, orbitofrontal superior medial cortex, insula R, posterior cingulate gyrus L, and cerebellum 9 L are endowed with different EC scores significantly. In the brain subsystems level, EC scores of DMN, prefrontal lobe, and cerebellum are aberrant in the ASD boys. Generally, the EC scores display widespread distribution of diseased regions in ASD brains. Meanwhile, the discovered regions and subsystems, such as MPFC, AMYG, INS, prefrontal lobe, and DMN, are engaged in social processing. Meanwhile, the CBCL externalizing problem scores are associated with EC scores.


Assuntos
Transtorno do Espectro Autista , Encéfalo , Mapeamento Encefálico , Eletroencefalografia , Humanos , Imageamento por Ressonância Magnética , Masculino , Vias Neurais
3.
Nature ; 598(7879): 188-194, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34616074

RESUMO

The cortico-basal ganglia-thalamo-cortical loop is one of the fundamental network motifs in the brain. Revealing its structural and functional organization is critical to understanding cognition, sensorimotor behaviour, and the natural history of many neurological and neuropsychiatric disorders. Classically, this network is conceptualized to contain three information channels: motor, limbic and associative1-4. Yet this three-channel view cannot explain the myriad functions of the basal ganglia. We previously subdivided the dorsal striatum into 29 functional domains on the basis of the topography of inputs from the entire cortex5. Here we map the multi-synaptic output pathways of these striatal domains through the globus pallidus external part (GPe), substantia nigra reticular part (SNr), thalamic nuclei and cortex. Accordingly, we identify 14 SNr and 36 GPe domains and a direct cortico-SNr projection. The striatonigral direct pathway displays a greater convergence of striatal inputs than the more parallel striatopallidal indirect pathway, although direct and indirect pathways originating from the same striatal domain ultimately converge onto the same postsynaptic SNr neurons. Following the SNr outputs, we delineate six domains in the parafascicular and ventromedial thalamic nuclei. Subsequently, we identify six parallel cortico-basal ganglia-thalamic subnetworks that sequentially transduce specific subsets of cortical information through every elemental node of the cortico-basal ganglia-thalamic loop. Thalamic domains relay this output back to the originating corticostriatal neurons of each subnetwork in a bona fide closed loop.


Assuntos
Gânglios da Base/citologia , Córtex Cerebral/citologia , Vias Neurais , Neurônios/citologia , Tálamo/citologia , Animais , Gânglios da Base/anatomia & histologia , Córtex Cerebral/anatomia & histologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tálamo/anatomia & histologia
4.
Nat Neurosci ; 24(11): 1506-1507, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34654921

Assuntos
Emoções , Vias Neurais
6.
Transl Psychiatry ; 11(1): 511, 2021 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620830

RESUMO

Major depressive disorder (MDD) is associated with abnormal neural circuitry. It can be measured by assessing functional connectivity (FC) at resting-state functional MRI, that may help identifying neural markers of MDD and provide further efficient diagnosis and monitor treatment outcomes. The main aim of the present study is to investigate, in an unbiased way, functional alterations in patients with MDD using a large multi-center dataset from the PsyMRI consortium including 1546 participants from 19 centers ( www.psymri.com ). After applying strict exclusion criteria, the final sample consisted of 606 MDD patients (age: 35.8 ± 11.9 y.o.; females: 60.7%) and 476 healthy participants (age: 33.3 ± 11.0 y.o.; females: 56.7%). We found significant relative hypoconnectivity within somatosensory motor (SMN), salience (SN) networks and between SMN, SN, dorsal attention (DAN), and visual (VN) networks in MDD patients. No significant differences were detected within the default mode (DMN) and frontoparietal networks (FPN). In addition, alterations in network organization were observed in terms of significantly lower network segregation of SMN in MDD patients. Although medicated patients showed significantly lower FC within DMN, FPN, and SN than unmedicated patients, there were no differences between medicated and unmedicated groups in terms of network organization in SMN. We conclude that the network organization of cortical networks, involved in processing of sensory information, might be a more stable neuroimaging marker for MDD than previously assumed alterations in higher-order neural networks like DMN and FPN.


Assuntos
Conectoma , Transtorno Depressivo Maior , Adulto , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/tratamento farmacológico , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Descanso , Adulto Jovem
7.
Nat Commun ; 12(1): 6114, 2021 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-34671042

RESUMO

In the hippocampal circuit CA3 input plays a critical role in the organization of CA1 population activity, both during learning and sleep. While integrated spatial representations have been observed across the two hemispheres of CA1, these regions lack direct connectivity and thus the circuitry responsible remains largely unexplored. Here we investigate the role of CA3 in organizing bilateral CA1 activity by blocking synaptic transmission at CA3 terminals through the inducible transgenic expression of tetanus toxin. Although the properties of single place cells in CA1 were comparable bilaterally, we find a decrease of ripple synchronization between left and right CA1 after silencing CA3. Further, during both exploration and rest, CA1 neuronal ensemble activity is less coordinated across hemispheres. This included degradation of the replay of previously explored spatial paths in CA1 during rest, consistent with the idea that CA3 bilateral projections integrate activity between left and right hemispheres and orchestrate bilateral hippocampal coding.


Assuntos
Região CA1 Hipocampal/fisiologia , Região CA3 Hipocampal/fisiologia , Lateralidade Funcional/fisiologia , Animais , Região CA1 Hipocampal/citologia , Região CA1 Hipocampal/metabolismo , Potenciais Pós-Sinápticos Excitadores/fisiologia , Camundongos , Vias Neurais/fisiologia , Células de Lugar/fisiologia , Descanso/fisiologia , Transmissão Sináptica/genética , Toxina Tetânica/genética , Vigília/fisiologia
8.
Neuron ; 109(20): 3312-3322.e5, 2021 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-34672984

RESUMO

Concurrent genetic neuromodulation and functional magnetic resonance imaging (fMRI) in primates has provided a valuable opportunity to assess the modified brain-wide operation in the resting state. However, its application to link the network operation with behavior still remains challenging. Here, we combined chemogenetic silencing of the primary somatosensory cortex (SI) with tactile fMRI and related behaviors in macaques. Focal chemogenetic silencing of functionally identified SI hand region impaired grasping behavior. The same silencing also attenuated hand stimulation-evoked fMRI signal at both the local silencing site and the anatomically and/or functionally connected downstream grasping network, suggesting altered network operation underlying the induced behavioral impairment. Furthermore, the hand region silencing unexpectedly disinhibited foot representation with accompanying behavioral hypersensitization. These results demonstrate that focal chemogenetic silencing with sensory fMRI in macaques unveils bidirectional network changes to generate multifaceted behavioral impairments, thereby opening a pivotal window toward elucidating the causal network operation underpinning higher brain functions in primates.


Assuntos
Técnicas Genéticas , Força da Mão , Córtex Somatossensorial/diagnóstico por imagem , Tato , Animais , , Neuroimagem Funcional , Mãos , Macaca fuscata , Imageamento por Ressonância Magnética , Vias Neurais/diagnóstico por imagem , Vias Neurais/metabolismo , Vias Neurais/fisiologia , Primatas , Córtex Somatossensorial/metabolismo , Córtex Somatossensorial/fisiologia
9.
Med Hypotheses ; 156: 110688, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34628112

RESUMO

Depression is the second leading cause of disability in the world. Despite developing some efficacious treatments, many patients do not respond to the treatment well due to the complexity of depression and unknown mechanisms involved in its pathogenesis. It has been reported that patients with major depressive disorder (MDD) experience autonomic dysfunctions in different aspects. Evidence suggests that modulation of the autonomic nervous system may improve depression. Von Economo neurons (VENs) are shown to be involved in the pathophysiology of some of the neurological and psychological diseases. VENs are also important for the "ego" formation, sense of empathy, intuition, and cognition. These neurons express a high level of adrenoreceptor alpha 1a, which confirms their role in the autonomic function. Here, based on some evidence, I propose the hypothesis that these neurons may play a role in depression, possibly through being involved in the autonomic function. More focused studies on VENs and their possible role in depression is suggested in future. This pathway may open a new window in the treatment of depression.


Assuntos
Transtorno Depressivo Maior , Sistema Nervoso Autônomo , Depressão , Humanos , Vias Neurais , Neurônios
10.
Elife ; 102021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34647521

RESUMO

Envisioning the future is intuitively linked to our ability to remember the past. Within the memory system, substantial work has demonstrated the involvement of the prefrontal cortex and the hippocampus in representing the past and present. Recent data shows that both the prefrontal cortex and the hippocampus encode future trajectories, which are segregated in time by alternating cycles of the theta rhythm. Here, we discuss how information is temporally organized by these brain regions supported by the medial septum, nucleus reuniens, and parahippocampal regions. Finally, we highlight a brain circuit that we predict is essential for the temporal segregation of future scenarios.


Assuntos
Encéfalo/fisiologia , Memória , Ritmo Teta , Animais , Antecipação Psicológica , Hipocampo/fisiologia , Humanos , Imaginação , Vias Neurais/fisiologia , Córtex Pré-Frontal/fisiologia , Fatores de Tempo
11.
BMC Psychiatry ; 21(1): 490, 2021 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-34615497

RESUMO

INTRODUCTION: Functional networks develop throughout adolescence when anorexia nervosa (AN) normally debuts. In AN, cerebral structural alterations are found in most brain regions and may be related to the observed functional brain changes. Few studies have investigated the functional networks of the brain in adolescent AN patients.. The aim of this explorative study was to investigate multiple functional networks in adolescent AN patients compared to healthy age-matched controls (HC) and the relationship with age, eating disorder symptoms and structural alterations. METHODS: Included were 29 female inpatients with restrictive AN, and 27 HC. All participants were between the ages of 12 to 18 years. Independent component analysis (ICA) identified 21 functional networks that were analyzed with multivariate and univariate analyses of components and group affiliation (AN vs HC). Age, age × group interaction and AN symptoms were included as covariates. Follow-up correlational analyses of selected components and structural measures (cortical thickness and subcortical volume) were carried out. RESULTS: Decreased functional connectivity (FC) in AN patients was found in one cortical network, involving mainly the precuneus, and identified as a default mode network (DMN). Cortical thickness in the precuneus was significantly correlated with functional connectivity in this network. Significant group differences were also found in two subcortical networks involving mainly the hippocampus and the amygdala respectively, and a significant interaction effect of age and group was found in both these networks. There were no significant associations between FC and the clinical measures used in the study. CONCLUSION: The findings from the present study may imply that functional alterations are related to structural alterations in selected regions and that the restricted food intake in AN patients disrupt normal age-related development of functional networks involving the amygdala and hippocampus.


Assuntos
Anorexia Nervosa , Adolescente , Anorexia Nervosa/diagnóstico por imagem , Encéfalo , Mapeamento Encefálico , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Vias Neurais/diagnóstico por imagem
12.
Nature ; 598(7879): 167-173, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34616065

RESUMO

Neuronal cell types are classically defined by their molecular properties, anatomy and functions. Although recent advances in single-cell genomics have led to high-resolution molecular characterization of cell type diversity in the brain1, neuronal cell types are often studied out of the context of their anatomical properties. To improve our understanding of the relationship between molecular and anatomical features that define cortical neurons, here we combined retrograde labelling with single-nucleus DNA methylation sequencing to link neural epigenomic properties to projections. We examined 11,827 single neocortical neurons from 63 cortico-cortical and cortico-subcortical long-distance projections. Our results showed unique epigenetic signatures of projection neurons that correspond to their laminar and regional location and projection patterns. On the basis of their epigenomes, intra-telencephalic cells that project to different cortical targets could be further distinguished, and some layer 5 neurons that project to extra-telencephalic targets (L5 ET) formed separate clusters that aligned with their axonal projections. Such separation varied between cortical areas, which suggests that there are area-specific differences in L5 ET subtypes, which were further validated by anatomical studies. Notably, a population of cortico-cortical projection neurons clustered with L5 ET rather than intra-telencephalic neurons, which suggests that a population of L5 ET cortical neurons projects to both targets. We verified the existence of these neurons by dual retrograde labelling and anterograde tracing of cortico-cortical projection neurons, which revealed axon terminals in extra-telencephalic targets including the thalamus, superior colliculus and pons. These findings highlight the power of single-cell epigenomic approaches to connect the molecular properties of neurons with their anatomical and projection properties.


Assuntos
Córtex Cerebral/citologia , Córtex Cerebral/metabolismo , Epigenoma , Epigenômica , Vias Neurais , Neurônios/classificação , Neurônios/metabolismo , Animais , Mapeamento Encefálico , Feminino , Masculino , Camundongos , Neurônios/citologia
13.
Nat Commun ; 12(1): 6016, 2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34650039

RESUMO

Models of cognitive function typically focus on the cerebral cortex and hence overlook functional links to subcortical structures. This view does not consider the role of the highly-conserved ascending arousal system's role and the computational capacities it provides the brain. We test the hypothesis that the ascending arousal system modulates cortical neural gain to alter the low-dimensional energy landscape of cortical dynamics. Here we use spontaneous functional magnetic resonance imaging data to study phasic bursts in both locus coeruleus and basal forebrain, demonstrating precise time-locked relationships between brainstem activity, low-dimensional energy landscapes, network topology, and spatiotemporal travelling waves. We extend our analysis to a cohort of experienced meditators and demonstrate locus coeruleus-mediated network dynamics were associated with internal shifts in conscious awareness. Together, these results present a view of brain organization that highlights the ascending arousal system's role in shaping both the dynamics of the cerebral cortex and conscious awareness.


Assuntos
Nível de Alerta , Encéfalo/fisiologia , Cognição , Vias Neurais , Adolescente , Adulto , Idoso , Atenção , Prosencéfalo Basal , Tronco Encefálico , Feminino , Humanos , Locus Cerúleo , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
18.
Nature ; 598(7879): 120-128, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34616061

RESUMO

Mammalian brain cells show remarkable diversity in gene expression, anatomy and function, yet the regulatory DNA landscape underlying this extensive heterogeneity is poorly understood. Here we carry out a comprehensive assessment of the epigenomes of mouse brain cell types by applying single-nucleus DNA methylation sequencing1,2 to profile 103,982 nuclei (including 95,815 neurons and 8,167 non-neuronal cells) from 45 regions of the mouse cortex, hippocampus, striatum, pallidum and olfactory areas. We identified 161 cell clusters with distinct spatial locations and projection targets. We constructed taxonomies of these epigenetic types, annotated with signature genes, regulatory elements and transcription factors. These features indicate the potential regulatory landscape supporting the assignment of putative cell types and reveal repetitive usage of regulators in excitatory and inhibitory cells for determining subtypes. The DNA methylation landscape of excitatory neurons in the cortex and hippocampus varied continuously along spatial gradients. Using this deep dataset, we constructed an artificial neural network model that precisely predicts single neuron cell-type identity and brain area spatial location. Integration of high-resolution DNA methylomes with single-nucleus chromatin accessibility data3 enabled prediction of high-confidence enhancer-gene interactions for all identified cell types, which were subsequently validated by cell-type-specific chromatin conformation capture experiments4. By combining multi-omic datasets (DNA methylation, chromatin contacts, and open chromatin) from single nuclei and annotating the regulatory genome of hundreds of cell types in the mouse brain, our DNA methylation atlas establishes the epigenetic basis for neuronal diversity and spatial organization throughout the mouse cerebrum.


Assuntos
Encéfalo/citologia , Metilação de DNA , Epigenoma , Epigenômica , Neurônios/classificação , Neurônios/metabolismo , Análise de Célula Única , Animais , Atlas como Assunto , Encéfalo/metabolismo , Cromatina/química , Cromatina/genética , Cromatina/metabolismo , Citosina/química , Citosina/metabolismo , Conjuntos de Dados como Assunto , Giro Denteado/citologia , Elementos Facilitadores Genéticos/genética , Perfilação da Expressão Gênica , Hipocampo/citologia , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Biológicos , Vias Neurais , Neurônios/citologia
19.
Nat Commun ; 12(1): 5185, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465771

RESUMO

Parkinson's disease (PD) is characterised by the emergence of beta frequency oscillatory synchronisation across the cortico-basal-ganglia circuit. The relationship between the anatomy of this circuit and oscillatory synchronisation within it remains unclear. We address this by combining recordings from human subthalamic nucleus (STN) and internal globus pallidus (GPi) with magnetoencephalography, tractography and computational modelling. Coherence between supplementary motor area and STN within the high (21-30 Hz) but not low (13-21 Hz) beta frequency range correlated with 'hyperdirect pathway' fibre densities between these structures. Furthermore, supplementary motor area activity drove STN activity selectively at high beta frequencies suggesting that high beta frequencies propagate from the cortex to the basal ganglia via the hyperdirect pathway. Computational modelling revealed that exaggerated high beta hyperdirect pathway activity can provoke the generation of widespread pathological synchrony at lower beta frequencies. These findings suggest a spectral signature and a pathophysiological role for the hyperdirect pathway in PD.


Assuntos
Vias Neurais , Doença de Parkinson/fisiopatologia , Estudos de Coortes , Globo Pálido/química , Globo Pálido/fisiopatologia , Humanos , Magnetoencefalografia , Córtex Motor/química , Córtex Motor/fisiopatologia , Núcleo Subtalâmico/química , Núcleo Subtalâmico/fisiopatologia
20.
PLoS Biol ; 19(9): e3001407, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34591838

RESUMO

Mathematical learning deficits are defined as a neurodevelopmental disorder (dyscalculia) in the International Classification of Diseases. It is not known, however, how such deficits emerge in the course of early brain development. Here, we conducted functional and structural magnetic resonance imaging (MRI) experiments in 3- to 6-year-old children without formal mathematical learning experience. We followed this sample until the age of 7 to 9 years, identified individuals who developed deficits, and matched them to a typically developing control group using comprehensive behavioral assessments. Multivariate pattern classification distinguished future cases from controls with up to 87% accuracy based on the regional functional activity of the right posterior parietal cortex (PPC), the network-level functional activity of the right dorsolateral prefrontal cortex (DLPFC), and the effective functional and structural connectivity of these regions. Our results indicate that mathematical learning deficits originate from atypical development of a frontoparietal network that is already detectable in early childhood.


Assuntos
Encéfalo/patologia , Discalculia/fisiopatologia , Vias Neurais/patologia , Mapeamento Encefálico , Criança , Desenvolvimento Infantil , Pré-Escolar , Discalculia/diagnóstico , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Lobo Parietal , Córtex Pré-Frontal
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