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1.
Proc Natl Acad Sci U S A ; 121(15): e2315167121, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38557177

RESUMO

The default mode network (DMN) is a large-scale brain network known to be suppressed during a wide range of cognitive tasks. However, our comprehension of its role in naturalistic and unconstrained behaviors has remained elusive because most research on the DMN has been conducted within the restrictive confines of MRI scanners. Here, we use multisite GCaMP (a genetically encoded calcium indicator) fiber photometry with simultaneous videography to probe DMN function in awake, freely exploring rats. We examined neural dynamics in three core DMN nodes-the retrosplenial cortex, cingulate cortex, and prelimbic cortex-as well as the anterior insula node of the salience network, and their association with the rats' spatial exploration behaviors. We found that DMN nodes displayed a hierarchical functional organization during spatial exploration, characterized by stronger coupling with each other than with the anterior insula. Crucially, these DMN nodes encoded the kinematics of spatial exploration, including linear and angular velocity. Additionally, we identified latent brain states that encoded distinct patterns of time-varying exploration behaviors and found that higher linear velocity was associated with enhanced DMN activity, heightened synchronization among DMN nodes, and increased anticorrelation between the DMN and anterior insula. Our findings highlight the involvement of the DMN in collectively and dynamically encoding spatial exploration in a real-world setting. Our findings challenge the notion that the DMN is primarily a "task-negative" network disengaged from the external world. By illuminating the DMN's role in naturalistic behaviors, our study underscores the importance of investigating brain network function in ecologically valid contexts.


Assuntos
Rede de Modo Padrão , Roedores , Ratos , Animais , Córtex Cerebral , Encéfalo/diagnóstico por imagem , Giro do Cíngulo/diagnóstico por imagem , Mapeamento Encefálico , Imageamento por Ressonância Magnética , Rede Nervosa/diagnóstico por imagem
2.
PLoS One ; 19(4): e0297669, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38598455

RESUMO

Capturing how the Caenorhabditis elegans connectome structure gives rise to its neuron functionality remains unclear. It is through fiber symmetries found in its neuronal connectivity that synchronization of a group of neurons can be determined. To understand these we investigate graph symmetries and search for such in the symmetrized versions of the forward and backward locomotive sub-networks of the Caenorhabditi elegans worm neuron network. The use of ordinarily differential equations simulations admissible to these graphs are used to validate the predictions of these fiber symmetries and are compared to the more restrictive orbit symmetries. Additionally fibration symmetries are used to decompose these graphs into their fundamental building blocks which reveal units formed by nested loops or multilayered fibers. It is found that fiber symmetries of the connectome can accurately predict neuronal synchronization even under not idealized connectivity as long as the dynamics are within stable regimes of simulations.


Assuntos
Caenorhabditis elegans , Conectoma , Animais , Caenorhabditis elegans/fisiologia , Rede Nervosa/fisiologia , Neurônios/fisiologia
3.
Nat Commun ; 15(1): 2185, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38467606

RESUMO

The existence of a multiple-demand cortical system with an adaptive, domain-general, role in cognition has been proposed, but the underlying dynamic mechanisms and their links to cognitive control abilities are poorly understood. Here we use a probabilistic generative Bayesian model of brain circuit dynamics to determine dynamic brain states across multiple cognitive domains, independent datasets, and participant groups, including task fMRI data from Human Connectome Project, Dual Mechanisms of Cognitive Control study and a neurodevelopment study. We discover a shared brain state across seven distinct cognitive tasks and found that the dynamics of this shared brain state predicted cognitive control abilities in each task. Our findings reveal the flexible engagement of dynamic brain processes across multiple cognitive domains and participant groups, and uncover the generative mechanisms underlying the functioning of a domain-general cognitive operating system. Our computational framework opens promising avenues for probing neurocognitive function and dysfunction.


Assuntos
Encéfalo , Conectoma , Humanos , Teorema de Bayes , Encéfalo/diagnóstico por imagem , Cognição , Modelos Estatísticos , Imageamento por Ressonância Magnética , Rede Nervosa
4.
Artigo em Inglês | MEDLINE | ID: mdl-38451768

RESUMO

Diagnosing and treating dementia, including mild cognitive impairment (MCI), is challenging due to diverse disease types and overlapping symptoms. Early MCI detection is vital as it can precede dementia, yet distinguishing it from later stage dementia is intricate due to subtle symptoms. The primary objective of this study is to adopt a complex network perspective to unravel the underlying pathophysiological mechanisms of dementia-related disorders. Leveraging the extensive availability of electroencephalogram (EEG) data, our study focuses on the meticulous identification and analysis of EEG-based brain functional network (BFNs) associated with dementia-related disorders. To achieve this, we employ the Phase Lag Index (PLI) as a connectivity measure, offering a comprehensive view of neural interactions. To enhance the analytical rigor, we introduce a data-driven threshold selection technique. This innovative approach allows us to compare the topological structures of the formulated BFNs using complex network measures quantitatively and statistically. Furthermore, we harness the power of these BFNs by utilizing them as pre-defined graph inputs for a Graph Convolution Network (GCN-net) based approach. The results demonstrate that graph theory metrics, such as the rich-club coefficient, transitivity, and assortativity coefficients, effectively distinguish between MCI, Alzheimer's disease (AD) and vascular dementia (VD). Furthermore, GCN-net achieves high accuracy (95.07% delta, 80.62% theta) and F1-scores (0.92 delta, 0.67 theta), highlighting the effectiveness of EEG-based BFNs in the analysis of dementia-related disorders.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Rede Nervosa , Encéfalo , Eletroencefalografia/métodos , Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/diagnóstico
5.
Neuroimage ; 290: 120576, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38490583

RESUMO

To elucidate how time of day, sex, and age affect functional connectivity (FC) in mice, we aimed to examine whether the mouse functional connectome varied with the day/night cycle and whether it depended on sex and age. We explored C57Bl6/J mice (6♀ and 6♂) at mature age (5 ± 1 months) and middle-age (14 ± 1 months). Each mouse underwent Blood Oxygen-Level-Dependent (BOLD) resting-state functional MRI (rs-fMRI) on a 7T scanner at four different times of the day, two under the light condition and two under the dark condition. Data processing consisted of group independent component analysis (ICA) and region-level analysis using resting-state networks (RSNs) derived from literature. Linear mixed-effect models (LMEM) were used to assess the effects of sex, lighting condition and their interactions for each RSN obtained with group-ICA (RSNs-GICA) and six bilateral RSNs adapted from literature (RSNs-LIT). Our study highlighted new RSNs in mice related to day/night alternation in addition to other networks already reported in the literature. In mature mice, we found sex-related differences in brain activation only in one RSNs-GICA comprising the cortical, hippocampal, midbrain and cerebellar regions of the right hemisphere. In males, brain activity was significantly higher in the left hippocampus, the retrosplenial cortex, the superior colliculus, and the cerebellum regardless of lighting condition; consistent with the role of these structures in memory formation and integration, sleep, and sex-differences in memory processing. Experimental constraints limited the analysis to the impact of light/dark cycle on the RSNs for middle-aged females. We detected significant activation in the pineal gland during the dark condition, a finding in line with the nocturnal activity of this gland. For the analysis of RSNs-LIT, new variables "sexage" (sex and age combined) and "edges" (pairs of RSNs) were introduced. FC was calculated as the Pearson correlation between two RSNs. LMEM revealed no effect of sexage or lighting condition. The FC depended on the edges, but there were no interaction effects between sexage, lighting condition and edges. Interaction effects were detected between i) sex and lighting condition, with higher FC in males under the dark condition, ii) sexage and edges with higher FC in male brain regions related to vision, memory, and motor action. We conclude that time of day and sex should be taken into account when designing, analyzing, and interpreting functional imaging studies in rodents.


Assuntos
Conectoma , Masculino , Feminino , Animais , Camundongos , Conectoma/métodos , Mapeamento Encefálico/métodos , Encéfalo/fisiologia , Giro do Cíngulo , Sono , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/fisiologia
6.
PLoS Comput Biol ; 20(3): e1011891, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38466752

RESUMO

Recent developments in experimental techniques have enabled simultaneous recordings from thousands of neurons, enabling the study of functional cell assemblies. However, determining the patterns of synaptic connectivity giving rise to these assemblies remains challenging. To address this, we developed a complementary, simulation-based approach, using a detailed, large-scale cortical network model. Using a combination of established methods we detected functional cell assemblies from the stimulus-evoked spiking activity of 186,665 neurons. We studied how the structure of synaptic connectivity underlies assembly composition, quantifying the effects of thalamic innervation, recurrent connectivity, and the spatial arrangement of synapses on dendrites. We determined that these features reduce up to 30%, 22%, and 10% of the uncertainty of a neuron belonging to an assembly. The detected assemblies were activated in a stimulus-specific sequence and were grouped based on their position in the sequence. We found that the different groups were affected to different degrees by the structural features we considered. Additionally, connectivity was more predictive of assembly membership if its direction aligned with the temporal order of assembly activation, if it originated from strongly interconnected populations, and if synapses clustered on dendritic branches. In summary, reversing Hebb's postulate, we showed how cells that are wired together, fire together, quantifying how connectivity patterns interact to shape the emergence of assemblies. This includes a qualitative aspect of connectivity: not just the amount, but also the local structure matters; from the subcellular level in the form of dendritic clustering to the presence of specific network motifs.


Assuntos
Neurônios , Tálamo , Neurônios/fisiologia , Simulação por Computador , Potenciais de Ação/fisiologia , Sinapses/fisiologia , Rede Nervosa/fisiologia , Modelos Neurológicos
7.
Adv Neurobiol ; 36: 639-657, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38468056

RESUMO

The conscious perception of pain is the result of dynamic interactions of neural activities from local brain regions to distributed brain networks. Mapping out the networks of functional connections between brain regions that form and disperse when an experimental participant received nociceptive stimulations allow to characterize the pattern of network connections related to the pain experience.Although the pattern of intra- and inter-areal connections across the brain are incredibly complex, they appear also largely scale free, with "fractal" connectivity properties reproducing at short and long-time scales. Our results combining intracranial recordings and functional imaging in humans during pain indicate striking similarities in the activity and topological representation of networks at different orders of temporality, with reproduction of patterns of activation from the millisecond to the multisecond range. The connectivity analyzed using graph theory on fMRI data was organized in four sets of brain regions matching those identified through iEEG (i.e., sensorimotor, default mode, central executive, and amygdalo-hippocampal).Here, we discuss similarities in brain network organization at different scales or "orders," in participants as they feel pain. Description of this fractal-like organization may provide clues about how our brain regions work together to create the perception of pain and how pain becomes chronic when its organization is altered.


Assuntos
Mapeamento Encefálico , Fractais , Humanos , Mapeamento Encefálico/métodos , Encéfalo , Imageamento por Ressonância Magnética/métodos , Dor , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologia
8.
PLoS Biol ; 22(2): e3002489, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38315722

RESUMO

The brain connectome is an embedded network of anatomically interconnected brain regions, and the study of its topological organization in mammals has become of paramount importance due to its role in scaffolding brain function and behavior. Unlike many other observable networks, brain connections incur material and energetic cost, and their length and density are volumetrically constrained by the skull. Thus, an open question is how differences in brain volume impact connectome topology. We address this issue using the MaMI database, a diverse set of mammalian connectomes reconstructed from 201 animals, covering 103 species and 12 taxonomy orders, whose brain size varies over more than 4 orders of magnitude. Our analyses focus on relationships between volume and modular organization. After having identified modules through a multiresolution approach, we observed how connectivity features relate to the modular structure and how these relations vary across brain volume. We found that as the brain volume increases, modules become more spatially compact and dense, comprising more costly connections. Furthermore, we investigated how spatial embedding shapes network communication, finding that as brain volume increases, nodes' distance progressively impacts communication efficiency. We identified modes of variation in network communication policies, as smaller and bigger brains show higher efficiency in routing- and diffusion-based signaling, respectively. Finally, bridging network modularity and communication, we found that in larger brains, modular structure imposes stronger constraints on network signaling. Altogether, our results show that brain volume is systematically related to mammalian connectome topology and that spatial embedding imposes tighter restrictions on larger brains.


Assuntos
Conectoma , Animais , Conectoma/métodos , Encéfalo , Mamíferos , Bases de Dados Factuais , Comunicação , Rede Nervosa
9.
Sci Rep ; 14(1): 3142, 2024 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326324

RESUMO

Exploring how the emergent functional connectivity (FC) relates to the underlying anatomy (structural connectivity, SC) is one of the major goals of modern neuroscience. At the macroscale level, no one-to-one correspondence between structural and functional links seems to exist. And we posit that to better understand their coupling, two key aspects should be considered: the directionality of the structural connectome and limitations in explaining networks functions through an undirected measure such as FC. Here, we employed an accurate directed SC of the mouse brain acquired through viral tracers and compared it with single-subject effective connectivity (EC) matrices derived from a dynamic causal model (DCM) applied to whole-brain resting-state fMRI data. We analyzed how SC deviates from EC and quantified their respective couplings by conditioning on the strongest SC links and EC links. We found that when conditioning on the strongest EC links, the obtained coupling follows the unimodal-transmodal functional hierarchy. Whereas the reverse is not true, as there are strong SC links within high-order cortical areas with no corresponding strong EC links. This mismatch is even more clear across networks; only within sensory motor networks did we observe connections that align in terms of both effective and structural strength.


Assuntos
Encéfalo , Conectoma , Camundongos , Animais , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/anatomia & histologia
10.
Hum Brain Mapp ; 45(2): e26587, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38339903

RESUMO

Recent years have seen growing interest in characterizing the properties of regional brain dynamics and their relationship to other features of brain structure and function. In particular, multiple studies have observed regional differences in the "timescale" over which activity fluctuates during periods of quiet rest. In the cerebral cortex, these timescales have been associated with both local circuit properties as well as patterns of inter-regional connectivity, including the extent to which each region exhibits widespread connectivity to other brain areas. In the current study, we build on prior observations of an association between connectivity and dynamics in the cerebral cortex by investigating the relationship between BOLD fMRI timescales and the modular organization of structural and functional brain networks. We characterize network community structure across multiple scales and find that longer timescales are associated with greater within-community functional connectivity and diverse structural connectivity. We also replicate prior observations of a positive correlation between timescales and structural connectivity degree. Finally, we find evidence for preferential functional connectivity between cortical areas with similar timescales. We replicate these findings in an independent dataset. These results contribute to our understanding of functional brain organization and structure-function relationships in the human brain, and support the notion that regional differences in cortical dynamics may in part reflect the topological role of each region within macroscale brain networks.


Assuntos
Encéfalo , Córtex Cerebral , Humanos , Encéfalo/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética , Descanso , Rede Nervosa/diagnóstico por imagem
11.
Science ; 383(6682): eadj9198, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38300992

RESUMO

Mapping single-neuron projections is essential for understanding brain-wide connectivity and diverse functions of the hippocampus (HIP). Here, we reconstructed 10,100 single-neuron projectomes of mouse HIP and classified 43 projectome subtypes with distinct projection patterns. The number of projection targets and axon-tip distribution depended on the soma location along HIP longitudinal and transverse axes. Many projectome subtypes were enriched in specific HIP subdomains defined by spatial transcriptomic profiles. Furthermore, we delineated comprehensive wiring diagrams for HIP neurons projecting exclusively within the HIP formation (HPF) and for those projecting to both intra- and extra-HPF targets. Bihemispheric projecting neurons generally projected to one pair of homologous targets with ipsilateral preference. These organization principles of single-neuron projectomes provide a structural basis for understanding the function of HIP neurons.


Assuntos
Axônios , Mapeamento Encefálico , Hipocampo , Neurônios , Animais , Camundongos , Axônios/fisiologia , Axônios/ultraestrutura , Hipocampo/ultraestrutura , Neurônios/classificação , Neurônios/ultraestrutura , Análise de Célula Única/métodos , Rede Nervosa , Masculino , Camundongos Endogâmicos C57BL
12.
Chaos ; 34(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38377288

RESUMO

Real neurons connect to each other non-randomly. These connectivity graphs can potentially impact the ability of networks to synchronize, along with the dynamics of neurons and the dynamics of their connections. How the connectivity of networks of conductance-based neuron models like the classical Hodgkin-Huxley model or the Morris-Lecar model impacts synchronizability remains unknown. One powerful tool to resolve the synchronizability of these networks is the master stability function (MSF). Here, we apply and extend the MSF approach to networks of Morris-Lecar neurons with conductance-based coupling to determine under which parameters and for which graphs the synchronous solutions are stable. We consider connectivity graphs with a constant non-zero row sum, where the MSF approach can be readily extended to conductance-based synapses rather than the more well-studied diffusive connectivity case, which primarily applies to gap junction connectivity. In this formulation, the synchronous solution is a single, self-coupled, or "autaptic" neuron. We find that the primary determining parameter for the stability of the synchronous solution is, unsurprisingly, the reversal potential, as it largely dictates the excitatory/inhibitory potential of a synaptic connection. However, the change between "excitatory" and "inhibitory" synapses is rapid, with only a few millivolts separating stability and instability of the synchronous state for most graphs. We also find that for specific coupling strengths (as measured by the global synaptic conductance), islands of synchronizability in the MSF can emerge for inhibitory connectivity. We verified the stability of these islands by direct simulation of pairs of neurons coupled with eigenvalues in the matching spectrum.


Assuntos
Modelos Neurológicos , Neurônios , Neurônios/fisiologia , Transmissão Sináptica/fisiologia , Simulação por Computador , Sinapses/fisiologia , Potenciais de Ação/fisiologia , Rede Nervosa/fisiologia
13.
Nature ; 627(8002): 157-164, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38418877

RESUMO

The accumulation of metabolic waste is a leading cause of numerous neurological disorders, yet we still have only limited knowledge of how the brain performs self-cleansing. Here we demonstrate that neural networks synchronize individual action potentials to create large-amplitude, rhythmic and self-perpetuating ionic waves in the interstitial fluid of the brain. These waves are a plausible mechanism to explain the correlated potentiation of the glymphatic flow1,2 through the brain parenchyma. Chemogenetic flattening of these high-energy ionic waves largely impeded cerebrospinal fluid infiltration into and clearance of molecules from the brain parenchyma. Notably, synthesized waves generated through transcranial optogenetic stimulation substantially potentiated cerebrospinal fluid-to-interstitial fluid perfusion. Our study demonstrates that neurons serve as master organizers for brain clearance. This fundamental principle introduces a new theoretical framework for the functioning of macroscopic brain waves.


Assuntos
Encéfalo , Líquido Cefalorraquidiano , Líquido Extracelular , Neurônios , Potenciais de Ação , Encéfalo/citologia , Encéfalo/metabolismo , Ondas Encefálicas/fisiologia , Líquido Cefalorraquidiano/metabolismo , Líquido Extracelular/metabolismo , Sistema Glinfático/metabolismo , Cinética , Rede Nervosa/fisiologia , Neurônios/metabolismo , Optogenética , Tecido Parenquimatoso/metabolismo , Íons/metabolismo
14.
Conscious Cogn ; 119: 103654, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38422760

RESUMO

The neural underpinnings of selfhood encompass pre-reflective and reflective self-experience. The former refers to a basic, immediate experience of being a self, while the latter involves cognition and introspection. Although neural correlates of reflective self-experience have been studied, the pre-reflective remains underinvestigated. This research aims to bridge this gap by comparatively investigating ERP correlates of reading first- vs. third-person pronouns - approximating pre-reflective self-experience - and self- vs. other-related adjectives - approximating reflective self-experience - in 30 healthy participants. We found differential neural engagement between pre-reflective and reflective self-experience at 254-310 ms post-stimulus onset. Source estimation suggested that our sensor-level results could be plausibly explained by the involvement of cortical midline structures and default mode network in the general sense of self but selective recruitment of anterior cingulate and top-down dorsal attention network in the pre-reflective self. These findings offer a deeper understanding of the experiential self, especially pre-reflective, providing a foundation for investigating self-disorders.


Assuntos
Encéfalo , Cognição , Humanos , Rede Nervosa , Mapeamento Encefálico , Eletroencefalografia , Imageamento por Ressonância Magnética
15.
Epilepsia ; 65(4): 961-973, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38306118

RESUMO

OBJECTIVE: Genetic generalized epilepsy (GGE) accounts for approximately 20% of adult epilepsy cases and is considered a disorder of large brain networks, involving both hemispheres. Most studies have not shown any difference in functional whole-brain network topology when compared to healthy controls. Our objective was to examine whether this preserved global network topology could hide local reorganizations that balance out at the global network level. METHODS: We recorded high-density electroencephalograms from 20 patients and 20 controls, and reconstructed the activity of 118 regions. We computed functional connectivity in windows free of interictal epileptiform discharges in broad, delta, theta, alpha, and beta frequency bands, characterized the network topology, and used the Hub Disruption Index (HDI) to quantify the topological reorganization. We examined the generalizability of our results by reproducing a 25-electrode clinical system. RESULTS: Our study did not reveal any significant change in whole-brain network topology among GGE patients. However, the HDI was significantly different between patients and controls in all frequency bands except alpha (p < .01, false discovery rate [FDR] corrected, d < -1), and accompanied by an increase in connectivity in the prefrontal regions and default mode network. This reorganization suggests that regions that are important in transferring the information in controls were less so in patients. Inversely, the crucial regions in patients are less so in controls. These findings were also found in delta and theta frequency bands when using 25 electrodes (p < .001, FDR corrected, d < -1). SIGNIFICANCE: In GGE patients, the overall network topology is similar to that of healthy controls but presents a balanced local topological reorganization. This reorganization causes the prefrontal areas and default mode network to be more integrated and segregated, which may explain executive impairment associated with GGE. Additionally, the reorganization distinguishes patients from controls even when using 25 electrodes, suggesting its potential use as a diagnostic tool.


Assuntos
Epilepsia Generalizada , Epilepsia , Adulto , Humanos , Rede Nervosa/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Eletroencefalografia/métodos , Mapeamento Encefálico , Epilepsia Generalizada/genética , Imageamento por Ressonância Magnética/métodos
16.
Epilepsia ; 65(4): 1115-1127, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38393301

RESUMO

OBJECTIVE: Structural-functional coupling (SFC) has shown great promise in predicting postsurgical seizure recurrence in patients with temporal lobe epilepsy (TLE). In this study, we aimed to clarify the global alterations in SFC in TLE patients and predict their surgical outcomes using SFC features. METHODS: This study analyzed presurgical diffusion and functional magnetic resonance imaging data from 71 TLE patients and 48 healthy controls (HCs). TLE patients were categorized into seizure-free (SF) and non-seizure-free (nSF) groups based on postsurgical recurrence. Individual functional connectivity (FC), structural connectivity (SC), and SFC were quantified at the regional and modular levels. The data were compared between the TLE and HC groups as well as among the TLE, SF, and nSF groups. The features of SFC, SC, and FC were categorized into three datasets: the modular SFC dataset, regional SFC dataset, and SC/FC dataset. Each dataset was independently integrated into a cross-validated machine learning model to classify surgical outcomes. RESULTS: Compared with HCs, the visual and subcortical modules exhibited decoupling in TLE patients (p < .05). Multiple default mode network (DMN)-related SFCs were significantly higher in the nSF group than in the SF group (p < .05). Models trained using the modular SFC dataset demonstrated the highest predictive performance. The final prediction model achieved an area under the receiver operating characteristic curve of .893 with an overall accuracy of .887. SIGNIFICANCE: Presurgical hyper-SFC in the DMN was strongly associated with postoperative seizure recurrence. Furthermore, our results introduce a novel SFC-based machine learning model to precisely classify the surgical outcomes of TLE.


Assuntos
Epilepsia do Lobo Temporal , Humanos , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/cirurgia , Rede de Modo Padrão , Rede Nervosa , Convulsões/diagnóstico por imagem , Convulsões/cirurgia , Imageamento por Ressonância Magnética/métodos , Resultado do Tratamento
17.
Nature ; 626(8001): 1073-1083, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38355792

RESUMO

Human cellular models of neurodegeneration require reproducibility and longevity, which is necessary for simulating age-dependent diseases. Such systems are particularly needed for TDP-43 proteinopathies1, which involve human-specific mechanisms2-5 that cannot be directly studied in animal models. Here, to explore the emergence and consequences of TDP-43 pathologies, we generated induced pluripotent stem cell-derived, colony morphology neural stem cells (iCoMoNSCs) via manual selection of neural precursors6. Single-cell transcriptomics and comparison to independent neural stem cells7 showed that iCoMoNSCs are uniquely homogenous and self-renewing. Differentiated iCoMoNSCs formed a self-organized multicellular system consisting of synaptically connected and electrophysiologically active neurons, which matured into long-lived functional networks (which we designate iNets). Neuronal and glial maturation in iNets was similar to that of cortical organoids8. Overexpression of wild-type TDP-43 in a minority of neurons within iNets led to progressive fragmentation and aggregation of the protein, resulting in a partial loss of function and neurotoxicity. Single-cell transcriptomics revealed a novel set of misregulated RNA targets in TDP-43-overexpressing neurons and in patients with TDP-43 proteinopathies exhibiting a loss of nuclear TDP-43. The strongest misregulated target encoded the synaptic protein NPTX2, the levels of which are controlled by TDP-43 binding on its 3' untranslated region. When NPTX2 was overexpressed in iNets, it exhibited neurotoxicity, whereas correcting NPTX2 misregulation partially rescued neurons from TDP-43-induced neurodegeneration. Notably, NPTX2 was consistently misaccumulated in neurons from patients with amyotrophic lateral sclerosis and frontotemporal lobar degeneration with TDP-43 pathology. Our work directly links TDP-43 misregulation and NPTX2 accumulation, thereby revealing a TDP-43-dependent pathway of neurotoxicity.


Assuntos
Esclerose Amiotrófica Lateral , Proteína C-Reativa , Proteínas de Ligação a DNA , Degeneração Lobar Frontotemporal , Rede Nervosa , Proteínas do Tecido Nervoso , Neurônios , Humanos , Esclerose Amiotrófica Lateral/metabolismo , Esclerose Amiotrófica Lateral/patologia , Proteína C-Reativa/metabolismo , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/metabolismo , Degeneração Lobar Frontotemporal/metabolismo , Degeneração Lobar Frontotemporal/patologia , Rede Nervosa/metabolismo , Rede Nervosa/patologia , Proteínas do Tecido Nervoso/metabolismo , Células-Tronco Neurais/citologia , Neuroglia/citologia , Neurônios/citologia , Neurônios/metabolismo , Reprodutibilidade dos Testes
18.
J Comput Neurosci ; 52(1): 39-71, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38381252

RESUMO

The computational resources of a neuromorphic network model introduced earlier are investigated in the context of such hierarchical systems as the mammalian visual cortex. It is argued that a form of ubiquitous spontaneous local convolution, driven by spontaneously arising wave-like activity-which itself promotes local Hebbian modulation-enables logical gate-like neural motifs to form into hierarchical feed-forward structures of the Hubel-Wiesel type. Extra-synaptic effects are shown to play a significant rôle in these processes. The type of logic that emerges is not Boolean, confirming and extending earlier findings on the logic of schizophrenia.


Assuntos
Modelos Neurológicos , Córtex Visual , Animais , Rede Nervosa , Mamíferos
19.
PLoS Comput Biol ; 20(2): e1011896, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38394341

RESUMO

Shared input to a population of neurons induces noise correlations, which can decrease the information carried by a population activity. Inhibitory feedback in recurrent neural networks can reduce the noise correlations and thus increase the information carried by the population activity. However, the activity of inhibitory neurons is costly. This inhibitory feedback decreases the gain of the population. Thus, depolarization of its neurons requires stronger excitatory synaptic input, which is associated with higher ATP consumption. Given that the goal of neural populations is to transmit as much information as possible at minimal metabolic costs, it is unclear whether the increased information transmission reliability provided by inhibitory feedback compensates for the additional costs. We analyze this problem in a network of leaky integrate-and-fire neurons receiving correlated input. By maximizing mutual information with metabolic cost constraints, we show that there is an optimal strength of recurrent connections in the network, which maximizes the value of mutual information-per-cost. For higher values of input correlation, the mutual information-per-cost is higher for recurrent networks with inhibitory feedback compared to feedforward networks without any inhibitory neurons. Our results, therefore, show that the optimal synaptic strength of a recurrent network can be inferred from metabolically efficient coding arguments and that decorrelation of the input by inhibitory feedback compensates for the associated increased metabolic costs.


Assuntos
Rede Nervosa , Transmissão Sináptica , Transmissão Sináptica/fisiologia , Potenciais de Ação/fisiologia , Reprodutibilidade dos Testes , Simulação por Computador , Rede Nervosa/fisiologia , Modelos Neurológicos , Redes Neurais de Computação , Inibição Neural/fisiologia
20.
Elife ; 122024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38407174

RESUMO

The Hydra nervous system is the paradigm of a 'simple nerve net'. Nerve cells in Hydra, as in many cnidarian polyps, are organized in a nerve net extending throughout the body column. This nerve net is required for control of spontaneous behavior: elimination of nerve cells leads to polyps that do not move and are incapable of capturing and ingesting prey (Campbell, 1976). We have re-examined the structure of the Hydra nerve net by immunostaining fixed polyps with a novel antibody that stains all nerve cells in Hydra. Confocal imaging shows that there are two distinct nerve nets, one in the ectoderm and one in the endoderm, with the unexpected absence of nerve cells in the endoderm of the tentacles. The nerve nets in the ectoderm and endoderm do not contact each other. High-resolution TEM (transmission electron microscopy) and serial block face SEM (scanning electron microscopy) show that the nerve nets consist of bundles of parallel overlapping neurites. Results from transgenic lines show that neurite bundles include different neural circuits and hence that neurites in bundles require circuit-specific recognition. Nerve cell-specific innexins indicate that gap junctions can provide this specificity. The occurrence of bundles of neurites supports a model for continuous growth and differentiation of the nerve net by lateral addition of new nerve cells to the existing net. This model was confirmed by tracking newly differentiated nerve cells.


Assuntos
Cnidários , Hydra , Animais , Rede Nervosa , Neurônios , Neuritos
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