Neural Circuits of Interoception

Trends in Neurosciences, Journal Year: 2020, Volume and Issue: 44(1), P. 17 - 28

Published: Dec. 29, 2020

Language: Английский

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Relating enhancer genetic variation across mammals to complex phenotypes using machine learning

Science, Journal Year: 2023, Volume and Issue: 380(6643)

Published: April 27, 2023

Protein-coding differences between species often fail to explain phenotypic diversity, suggesting the involvement of genomic elements that regulate gene expression such as enhancers. Identifying associations enhancers and phenotypes is challenging because enhancer activity can be tissue-dependent functionally conserved despite low sequence conservation. We developed Tissue-Aware Conservation Inference Toolkit (TACIT) associate candidate with species' using predictions from machine learning models trained on specific tissues. Applying TACIT motor cortex parvalbumin-positive interneuron neurological revealed dozens enhancer-phenotype associations, including brain size-associated interact genes implicated in microcephaly or macrocephaly. provides a foundation for identifying associated evolution any convergently evolved phenotype large group aligned genomes.

Language: Английский

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Selective vulnerability of layer 5a corticostriatal neurons in Huntington’s disease

Neuron, Journal Year: 2024, Volume and Issue: 112(6), P. 924 - 941.e10

Published: Jan. 17, 2024

The properties of the cell types that are selectively vulnerable in Huntington's disease (HD) cortex, nature somatic CAG expansions mHTT these cells, and their importance CNS circuitry have not been delineated. Here, we employed serial fluorescence-activated nuclear sorting (sFANS), deep molecular profiling, single-nucleus RNA sequencing (snRNA-seq) motor-cortex samples from thirteen predominantly early stage, clinically diagnosed HD donors selected cingulate, visual, insular, prefrontal cortices to demonstrate loss layer 5a pyramidal neurons HD. Extensive occur Betz layers 6a 6b resilient Retrograde tracing experiments macaque brains identify as corticostriatal cells. We propose enhanced expansion altered synaptic function act together cause disconnection selective neuronal vulnerability cerebral cortex.

Language: Английский

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Diffusion Tensor Imaging in Parkinson's Disease and Parkinsonian Syndrome: A Systematic Review

Frontiers in Neurology, Journal Year: 2020, Volume and Issue: 11

Published: Sept. 25, 2020

Diffusion tensor imaging allows measuring fractional anisotropy and similar microstructural indices of the brain white matter. Lower than normal is associated with loss integrity neurodegeneration. Previous diffusion in Parkinson's Disease have demonstrated a multifocal pattern abnormal matter structures tracts. However, not considered diagnostic marker for earliest disease since anisotropic alterations present temporally divergent during course. This article reviews previous studies disease, comparison recent analyses based on datasets from progression markers initiative (PPMI) – large multicenter cohort research, aims to explain complex detected over also discusses challenges utility detecting changes dopaminergic nuclei pathways, roles as longitudinal tracking treatment effects, differentiation among Parkinsonism.

Language: Английский

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The fractal brain: scale-invariance in structure and dynamics

Cerebral Cortex, Journal Year: 2022, Volume and Issue: 33(8), P. 4574 - 4605

Published: Sept. 26, 2022

Abstract The past 40 years have witnessed extensive research on fractal structure and scale-free dynamics in the brain. Although considerable progress has been made, a comprehensive picture yet to emerge, needs further linking mechanistic account of brain function. Here, we review these concepts, connecting observations across different levels organization, from both structural functional perspective. We argue that, paradoxically, level cortical circuits is least understood point view perhaps best studied dynamical one. link about scale-freeness fractality with evidence that environment provides constraints may explain usefulness Moreover, discuss behavior exhibits properties, likely emerging similarly organized dynamics, enabling an organism thrive shares same organizational principles. Finally, sparse for try speculate consequences computation. These properties endow computational capabilities transcend current models neural computation could hold key unraveling how constructs percepts generates behavior.

Language: Английский

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Improved sensitivity and microvascular weighting of 3T laminar fMRI with GE-BOLD using NORDIC and phase regression

NeuroImage, Journal Year: 2023, Volume and Issue: 271, P. 120011 - 120011

Published: March 11, 2023

Functional MRI with spatial resolution in the submillimeter domain enables measurements of activation across cortical layers humans. This is valuable as different types computations, e.g., feedforward versus feedback related activity, take place layers. Laminar fMRI studies have almost exclusively employed 7T scanners to overcome reduced signal stability associated small voxels. However, such systems are relatively rare and only a subset those clinically approved. In present study, we examined if feasibility laminar at 3T could be improved by use NORDIC denoising phase regression.5 healthy subjects were scanned on Siemens MAGNETOM Prisma scanner. To assess across-session reliability, each subject was 3-8 sessions 3-4 consecutive days. A 3D gradient echo EPI (GE-EPI) sequence used for BOLD acquisitions (voxel size 0.82 mm isotopic, TR = 2.2 s) using block design finger tapping paradigm. applied magnitude time series limitations temporal signal-to-noise ratio (tSNR) denoised subsequently correct large vein contamination through regression.NORDIC resulted tSNR values comparable or higher than commonly observed 7T. Layer-dependent profiles thus extracted robustly, within sessions, from regions interest located hand knob primary motor cortex (M1). Phase regression led substantially superficial bias obtained layer profiles, although residual macrovascular contribution remained. We believe results support an 3T.

Language: Английский

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Betz cells of the primary motor cortex

The Journal of Comparative Neurology, Journal Year: 2024, Volume and Issue: 532(1)

Published: Jan. 1, 2024

Abstract Betz cells, named in honor of Volodymyr (1834–1894), who described them as “giant pyramids” the primary motor cortex primates and other mammalian species, are layer V extratelencephalic projection (ETP) neurons that directly innervate α‐motoneurons brainstem spinal cord. Despite their large volume circumferential dendritic architecture, to date, no single molecular criterion has been established unequivocally distinguishes adult cells from ETP neurons. In primates, transcriptional signatures suggest presence at least two neuron clusters contain mature cells; these characterized by an abundance axon guidance oxidative phosphorylation transcripts. How neurodevelopmental programs drive distinct positional morphological features humans remains unknown. display a biphasic firing pattern involving early cessation followed delayed sustained acceleration spike frequency magnitude. Few cell type‐specific transcripts electrophysiological characteristics conserved between rodent primate cells. This implications for modeling disorders affect humans, such amyotrophic lateral sclerosis (ALS). Perhaps vulnerability ALS is linked evolution neural networks fine control reflected morphomolecular architecture human cortex, including Here, we discuss histological, molecular, functional data concerning position emerging taxonomy across diverse species role neurological disorders.

Language: Английский

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Neurodegenerative Diseases: Unraveling the Heterogeneity of Astrocytes

Cells, Journal Year: 2024, Volume and Issue: 13(11), P. 921 - 921

Published: May 27, 2024

The astrocyte population, around 50% of human brain cells, plays a crucial role in maintaining the overall health and functionality central nervous system (CNS). Astrocytes are vital orchestrating neuronal development by releasing synaptogenic molecules eliminating excessive synapses. They also modulate excitability contribute to CNS homeostasis, promoting survival clearance neurotransmitters, transporting metabolites, secreting trophic factors. highly heterogeneous respond injuries diseases through process known as reactive astrogliosis, which can both inflammation its resolution. Recent evidence has revealed remarkable alterations transcriptomes response several diseases, identifying at least two distinct phenotypes called A1 or neurotoxic A2 neuroprotective astrocytes. However, due vast heterogeneity these it is limited classify them into only phenotypes. This review explores various physiological pathophysiological roles, potential markers, pathways that might be activated different astrocytic Furthermore, we discuss main neurodegenerative identify therapeutic strategies. Understanding underlying mechanisms differentiation imbalance population will allow identification specific biomarkers timely approaches diseases.

Language: Английский

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Adaptive structural changes in the motor cortex and white matter in Parkinson’s disease

Acta Neuropathologica, Journal Year: 2022, Volume and Issue: 144(5), P. 861 - 879

Published: Sept. 2, 2022

Parkinson's disease (PD) is a movement disorder characterized by the early loss of nigrostriatal dopaminergic pathways producing significant network changes impacting motor coordination. Recently three stages PD have been proposed (a silent period when begins, prodromal with subtle focal manifestations, and clinical PD) evidence that cortex abnormalities occur to produce PD[8]. We directly assess structural in primary corticospinal tract using parallel analyses longitudinal cross-sectional pathological cohorts thought represent different PD. 18F-FP-CIT positron emission tomography features identified patients idiopathic rapid-eye-movement sleep behaviour (n = 8) developed signs Longitudinal diffusion tensor imaging before after development showed higher fractional anisotropy compared controls, indicating adaptive networks concert dopamine loss. Histological white matter underlying progressive disorientation axons segmental replacement neurofilaments α-synuclein, enlargement myelinating oligodendrocytes increased density their precursors. There was no neurons or late pathologically confirmed although there were cortical increases neuronal neurofilament light chain myelin proteins association α-synuclein accumulation. Our results collectively provide direct impact on its output begins stage These become considerable as advances potentially contributing

Language: Английский

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Mapping microstructural gradients of the human striatum in normal aging and Parkinson’s disease

Science Advances, Journal Year: 2022, Volume and Issue: 8(28)

Published: July 15, 2022

Mapping structural spatial change (i.e., gradients) in the striatum is essential for understanding function of basal ganglia both health and disease. We developed a method to identify quantify gradients microstructure single human brain vivo. found putamen caudate nucleus that were robust across individuals, clinical conditions, datasets. By exploiting multiparametric quantitative MRI, we distinct, spatially dependent, aging-related alterations water content iron concentration. Furthermore, cortico-striatal microstructural covariation, showing relations between striatal cortical hierarchy. In Parkinson’s disease (PD) patients, abnormal putamen, revealing changes posterior explain patients’ dopaminergic loss motor dysfunction. Our work provides noninvasive approach studying varying, structure-function relationship vivo, normal aging PD.

Language: Английский

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