Topic modeling analysis of the Allen Human Brain Atlas

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 26, 2025

The human brain is a complex interconnected structure controlling all elementary and high-level cognitive tasks. It composed of many regions that exhibit specific distributions cell types distinct patterns functional connections. This complexity rooted in differential transcription. constituent different express distinctive combinations genes as they develop mature, ultimately shaping their state adulthood. How precisely the genetic information anatomical structures connected to underlying biological functions remains an open question modern neuroscience. A major challenge identification "universal patterns", which do not depend on particular individual, but are instead basic structural properties shared by brains. Despite vast amount gene expression data available at both bulk single-cell levels, this task challenging, mainly due lack suitable mining tools. In paper, we propose approach address issue based hierarchical version Stochastic Block Modeling. Thanks its choice priors, method particularly effective identifying these universal features. We use laboratory test our algorithm dataset obtained from six independent brains Allen Human Brain Atlas. show proposed indeed able identify much better than more traditional algorithms such Latent Dirichlet Allocation or Weighted Correlation Network Analysis. probabilistic association between samples find well represents known organization. Moreover, leveraging peculiar "fuzzy" sets with method, examples transcriptional post-transcriptional pathways associated regions, highlighting potential approach.

Language: Английский

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Identification of a Glutamatergic Claustrum-Anterior Cingulate Cortex Circuit for Visceral Pain Processing

Journal of Neuroscience, Journal Year: 2022, Volume and Issue: 42(43), P. 8154 - 8168

Published: Sept. 13, 2022

Chronic visceral pain is a major challenge for both patients and health providers. Although the central sensitization of brain thought to play an important role in development pain, detailed neural circuits remain largely unknown. Using well-established chronic hypersensitivity model induced by neonatal maternal deprivation (NMD) male mice, we identified distinct pathway whereby claustrum (CL) glutamatergic neuron projecting anterior cingulate cortex (ACC) critical but not CFA-evoked inflammatory pain. By combination vivo circuit-dissecting extracellular electrophysiological approaches related electromyographic (EMG) recordings, demonstrated that optogenetic inhibition CL activity suppressed ACC NMD mice whereas selective activation enhanced evoked control mice. Further, studies demonstrate causal link between such neuronal behaviors. Chemogenetic or activities reversed effects manipulation on responses. Importantly, molecular detection showed significantly enhances expression NMDA receptors activated CaMKIIα postsynaptic density (PSD) region. Together, our data establish functional CL→ACC neurons gating thus providing potential treatment strategy SIGNIFICANCE STATEMENT Studies have shown plays However, it as yet unknown whether there specific region circuit helps distinguish somatic The present study demonstrates maybe responding colorectal distention (CRD) rather than stimulation projection regulates Furthermore, excessive overactive were observed with these findings reveal novel circuity underlying

Language: Английский

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The claustrum-prelimbic cortex circuit through dynorphin/κ-opioid receptor signaling underlies depression-like behaviors associated with social stress etiology

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Nov. 30, 2023

Ample evidence has suggested the stress etiology of depression, but underlying mechanism is not fully understood yet. Here, we report that chronic social defeat (CSDS) attenuates excitatory output claustrum (CLA) to prelimbic cortex (PL) through dynorphin/κ-opioid receptor (KOR) signaling, being critical for depression-related behaviors in male mice. The CSDS preferentially impairs from CLA onto parvalbumin (PV) PL, leading PL micronetwork dysfunction by disinhibiting pyramidal neurons (PNs). Optogenetic activation or inhibition this circuit suppresses promotes depressive-like behaviors, which reversed chemogenetic PV neurons. Notably, manipulating dynorphin/KOR signaling CLA-PL projecting terminals controls suppressed promoted optogenetic circuit. Thus, study reveals both depression and possibly therapeutic interventions targeting

Language: Английский

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The functional connectivity of the human claustrum, according to the Human Connectome Project database

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(4), P. e0298349 - e0298349

Published: April 18, 2024

The claustrum is an irregular and fine sheet of grey matter in the basolateral telencephalon present almost all mammals. has been object several studies using animal models and, more recently, human beings neuroimaging. One most extended cognitive processes attributed to salience process, which also related insular cortex. In same way, with subjects functional magnetic resonance imaging have reported coactivation claustrum/insular cortex integration sensory signals. This left or right asymmetry task literature neurological disorders such as Alzheimer's disease schizophrenia, relating severity delusions reduction claustral volume. We a connectivity study claustrum. Resting-state anatomical MRI data from 100 healthy were analyzed; taken Human Connectome Project (HCP, NIH Blueprint: Project), 2x2x2 mm3 voxel resolution. hypothesize that 1) node involved different brain networks, 2) pattern cortex's pattern, 3) claustrum's connectivity. Our findings include at least three networks found between claustrum, frontoparietal network, default mode network distinctive attribute. dorsal attention supports hypothesis asymmetry. These provide evidence, suggesting coupled serving together instantiate new states by flexibly modulating interacting other control processing networks.

Language: Английский

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Localization of stuttering based on causal brain lesions

Brain, Journal Year: 2024, Volume and Issue: 147(6), P. 2203 - 2213

Published: May 27, 2024

Stuttering affects approximately 1 in 100 adults and can result significant communication problems social anxiety. It most often occurs as a developmental disorder but also be caused by focal brain damage. These latter cases may lend unique insight into the regions causing stuttering. Here, we investigated neuroanatomical substrate of stuttering using three independent datasets: (i) case reports from published literature acquired neurogenic following stroke (n = 20, 14 males/six females, 16-77 years); (ii) clinical single study cohort with 13 males/seven 45-87 (iii) persistent 18-43 years). We used first two datasets lesion network mapping to test whether lesions map common network. then third dataset this lesion-based was relevant In our dataset, found that occurred multiple heterogeneous regions, these locations were all functionally connected centred around left putamen, including claustrum, amygdalostriatal transition area other adjacent areas. This finding shown specific for (PFWE < 0.05) reproducible patients stroke-induced 0.05), resulting across both datasets. Within network, association between grey matter volume impact posteroventral extending claustrum 0.05). conclude area. The symptom severity suggests shared neuroanatomy aetiologies.

Language: Английский

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The Constrained Disorder Principle May Account for Consciousness

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(3), P. 209 - 209

Published: Feb. 23, 2024

There is still controversy surrounding the definition and mechanisms of consciousness. The constrained disorder principle (CDP) defines complex systems by their dynamic borders, limiting inherent disorder. In line with CDP, brain exhibits a bounded borders essential for proper function, efficient energy use, life support under continuous perturbations. brain’s variability contributes to its adaptability flexibility. Neuronal signal challenges association structures consciousness methods assessing present paper discusses some theories about consciousness, emphasizing failure explain variability. This describes how CDP accounts consciousness’s variability, complexity, entropy, uncertainty. Using newly developed second-generation artificial intelligence systems, we describe CDP-based platforms may improve disorders (DoC) accounting platform could be used response current interventions develop new therapeutic regimens patients DoC in future studies.

Language: Английский

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Self-Entropic Broadening Theory: Toward a New Understanding of Self and Behavior Change Informed by Psychedelics and Psychosis

Pharmacological Reviews, Journal Year: 2022, Volume and Issue: 74(4), P. 984 - 1029

Published: Sept. 16, 2022

The extremes of human experiences, such as those occasioned by classic psychedelics and psychosis, provide a rich contrast for understanding how components these experiences impact well-being. In recent years, research has suggested that display the potential to promote positive enduring psychologic behavioral changes in clinical nonclinical populations. Paradoxically, have been described psychotomimetics. This review offers putative solution this paradox providing theory often facilitate persistent increases well-being, whereas psychosis leads down "darker" path. will be done an overview overlap between states (i.e., entropic processing) their core differences self-focus). brief, processing can defined enhanced overall attentional scope decreased predictability stimuli facilitating hyperassociative style thinking. However, outcomes vary depending on level self-focus, or degree which associations information being processed are evaluated self-referential manner. We also describe points with less extreme creative thinking emotion-induction. Self-entropic broadening heuristically valuable perspective lasting effects relation other creating novel synthesis contemporary theories psychology. SIGNIFICANCE STATEMENT: provides examining psychedelic-psychotomimetic paradox, therapeutic, yet mimic symptoms psychosis. It posits framework transdiagnostic applicability psychedelics. hope model invigorates field more rigorous comparisons psychedelic-induced further examinations long-term change. As psychedelic future psychiatry appears imminent, addresses long-standing questions is crucial.

Language: Английский

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Pathobiology of Cognitive Impairment in Parkinson Disease: Challenges and Outlooks

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 25(1), P. 498 - 498

Published: Dec. 29, 2023

Cognitive impairment (CI) is a characteristic non-motor feature of Parkinson disease (PD) that poses severe burden on the patients and caregivers, yet relatively little known about its pathobiology. deficits are evident throughout course PD, with around 25% subtle cognitive decline mild CI (MCI) at time diagnosis up to 83% developing dementia after 20 years. The heterogeneity phenotypes suggests common neuropathological process, characterized by progressive degeneration dopaminergic striatonigral system many other neuronal systems, results not only in structural but also extensive changes functional network activities neurotransmitter dysfunctions. Modern neuroimaging studies revealed multilocular cortical subcortical atrophies alterations intrinsic connectivities. decreased connectivity (FC) default mode (DMN) bilateral prefrontal cortex affected already before development clinical absence changes. Longitudinal associated frontostriatal limbic affections, white matter microlesions between multiple networks, including thalamo-insular, frontoparietal attention cholinergic forebrain noradrenergic system. Superimposed Alzheimer-related (and concomitant) pathologies due interactions α-synuclein, tau-protein β-amyloid contribute pathogenesis both PD Lewy bodies (DLB). To further elucidate interaction pathomechanisms responsible for well-designed longitudinal clinico-pathological warranted supported fluid sophisticated imaging biomarkers as basis better early future disease-modifying therapies.

Language: Английский

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The Role of the Claustrum in Parkinson’s Disease and Vascular Parkinsonism: A Matter of Network?

Life, Journal Year: 2025, Volume and Issue: 15(2), P. 180 - 180

Published: Jan. 26, 2025

Background: The mechanisms underlying extrapyramidal disorders and their anatomical substrate have been extensively investigated. Recently, the role of claustrum in Parkinson’s disease other neurodegenerative conditions has better detailed. main aim this review was to summarize supporting evidence for degenerative vascular parkinsonism. Methods: anatomy, biology, supply, connections humans were identified described, providing involvement large- small-vessel disease. supply includes up three different sources from a single artery, middle cerebral it is known as territory with an intermediate hemodynamic risk. make sensory integrator relevant point several networks, consciousness movement planning. Conclusions: still incompletely explained structure. However, recent description its multiple indicate that involved diseases, including potential parkinsonism scarce, but might be field warranting future investigations.

Language: Английский

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The evolution of human-type consciousness – a by-product of mammalian innovation mechanism – a preliminary hypothesis

Frontiers in Psychology, Journal Year: 2025, Volume and Issue: 16

Published: April 17, 2025

Human consciousness is often viewed as one of the pinnacles evolution, with most theories positioning it an upgrade pre-existing cognitive skills. However, conscious perception, memory, action, and in some situations even decision-making, are inferior-less complex, slower, less accurate-than their nonconscious (subliminal) counterparts. The interface hypothesis challenges this perspective, proposing that human-type not advanced version earlier capacities but a novel function entered arena operational processes fundamentally changed its rules. According to hypothesis, neocortex emerged part innovation mechanism, where unpredictable, chaotic activity used generate alternative patterns. process cropping these alternatives from mediating them constrained, goal-oriented, linear control system requires serially functioning interface. Consciousness, suggested, arose byproduct or side effect interface, eventually expanding influence wide range functions. This perspective has significant implications for our understanding human cognition, creativity, distinctive consciousness, potentially bridging gap between neuroscientific findings phenomenological experiences consciousness.

Language: Английский

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