Sex and gender in neurodevelopmental conditions

Nature Reviews Neurology, Journal Year: 2023, Volume and Issue: 19(3), P. 136 - 159

Published: Feb. 6, 2023

Language: Английский

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An increase of inhibition drives the developmental decorrelation of neural activity

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Aug. 17, 2022

Throughout development, the brain transits from early highly synchronous activity patterns to a mature state with sparse and decorrelated neural activity, yet mechanisms underlying this process are poorly understood. The developmental transition has important functional consequences, as latter is thought allow for more efficient storage, retrieval, processing of information. Here, we show that, in mouse medial prefrontal cortex (mPFC), during first two postnatal weeks decorrelates following specific spatial patterns. This accompanied by concomitant tilting excitation-inhibition (E-I) ratio toward inhibition. Using optogenetic manipulations network modeling, that phenomena mechanistically linked, relative increase inhibition drives decorrelation activity. Accordingly, mice mimicking etiology neurodevelopmental disorders, subtle alterations E-I associated impairments correlational structure spike trains. Finally, capitalizing on EEG data newborn babies, an analogous takes place also human brain. Thus, changes control (de)correlation and, these means, its imbalance might contribute pathogenesis disorders.

Language: Английский

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mTOR-related synaptic pathology causes autism spectrum disorder-associated functional hyperconnectivity

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Oct. 19, 2021

Abstract Postmortem studies have revealed increased density of excitatory synapses in the brains individuals with autism spectrum disorder (ASD), a putative link to aberrant mTOR-dependent synaptic pruning. ASD is also characterized by atypical macroscale functional connectivity as measured resting-state fMRI (rsfMRI). These observations raise question whether excess causes ASD. Using rsfMRI, electrophysiology and silico modelling Tsc2 haploinsufficient mice, we show that spine associated -like stereotypies cortico-striatal hyperconnectivity. deficits are completely rescued pharmacological inhibition mTOR. Notably, further demonstrate children idiopathic exhibit analogous cortical-striatal hyperconnectivity, document this fingerprint enriched for ASD-dysregulated genes interacting mTOR or Tsc2. Finally, identified transcriptomic signature predominantly expressed subset autism, thereby defining segregable subtype. Our findings causally mTOR-related pathology large-scale network aberrations, revealing unifying multi-scale framework mechanistically reconciles developmental synaptopathy hyperconnectivity autism.

Language: Английский

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The neuropathology of autism: A systematic review of post-mortem studies of autism and related disorders

Neuroscience & Biobehavioral Reviews, Journal Year: 2021, Volume and Issue: 129, P. 35 - 62

Published: July 14, 2021

Language: Английский

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The Cerebellar Involvement in Autism Spectrum Disorders: From the Social Brain to Mouse Models

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(7), P. 3894 - 3894

Published: March 31, 2022

Autism spectrum disorders (ASD) are pervasive neurodevelopmental that include a variety of forms and clinical phenotypes. This heterogeneity complicates the experimental approaches to ASD etiology pathophysiology. To date, unifying theory these diseases is still missing. Nevertheless, intense work researchers clinicians in last decades has identified some hallmarks primary brain areas involved. Not surprisingly, part so-called “social brain”, those strictly connected them, were found be crucial, such as prefrontal cortex, amygdala, hippocampus, limbic system, dopaminergic pathways. With recent acknowledgment cerebellar contribution cognitive functions social brain, its involvement become unmistakable, though extent elucidated. In most cases, significant advances made possible by technological developments structural/functional assessment human using mouse models ASD. Mouse an invaluable tool get insights into molecular cellular counterparts disease, acting on specific genetic background generating ASD-like phenotype. Given multifaceted nature related studies, it often difficult navigate literature limit huge content questions. review fulfills need for organized, clear, state-of-the-art perspective ASD, from connections (which sites impairments) use monogenic models.

Language: Английский

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Increased fMRI connectivity upon chemogenetic inhibition of the mouse prefrontal cortex

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Feb. 25, 2022

Abstract While shaped and constrained by axonal connections, fMRI-based functional connectivity reorganizes in response to varying interareal input or pathological perturbations. However, the causal contribution of regional brain activity whole-brain fMRI network organization remains unclear. Here we combine neural manipulations, resting-state vivo electrophysiology probe how inactivation a cortical node causally affects brain-wide coupling mouse. We find that chronic inhibition medial prefrontal cortex (PFC) via overexpression potassium channel increases between inhibited area its direct thalamo-cortical targets. Acute chemogenetic PFC produces analogous patterns overconnectivity. Using electrophysiology, enhances low frequency (0.1–4 Hz) oscillatory power suppression firing not phase-locked slow rhythms, resulting increased δ band coherence areas exhibit These results provide evidence can counterintuitively increase enhanced, less-localized processes.

Language: Английский

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The aperiodic exponent of subthalamic field potentials reflects excitation/inhibition balance in Parkinsonism

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Feb. 22, 2023

Periodic features of neural time-series data, such as local field potentials (LFPs), are often quantified using power spectra. While the aperiodic exponent spectra is typically disregarded, it nevertheless modulated in a physiologically relevant manner and was recently hypothesised to reflect excitation/inhibition (E/I) balance neuronal populations. Here, we used cross-species vivo electrophysiological approach test E/I hypothesis context experimental idiopathic Parkinsonism. We demonstrate dopamine-depleted rats that exponents at 30–100 Hz subthalamic nucleus (STN) LFPs defined changes basal ganglia network activity; higher tally with lower levels STN neuron firing tipped towards inhibition. Using STN-LFPs recorded from awake Parkinson’s patients, show accompany dopaminergic medication deep brain stimulation (DBS) STN, consistent untreated manifesting reduced inhibition hyperactivity STN. These results suggest Parkinsonism reflects might be candidate biomarker for adaptive DBS.

Language: Английский

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A review of decreased sound tolerance in autism: Definitions, phenomenology, and potential mechanisms

Neuroscience & Biobehavioral Reviews, Journal Year: 2020, Volume and Issue: 121, P. 1 - 17

Published: Dec. 4, 2020

Language: Английский

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Brain mapping across 16 autism mouse models reveals a spectrum of functional connectivity subtypes

Molecular Psychiatry, Journal Year: 2021, Volume and Issue: 26(12), P. 7610 - 7620

Published: Aug. 11, 2021

Autism Spectrum Disorder (ASD) is characterized by substantial, yet highly heterogeneous abnormalities in functional brain connectivity. However, the origin and significance of this phenomenon remain unclear. To unravel ASD connectopathy relate it to underlying etiological heterogeneity, we carried out a bi-center cross-etiological investigation fMRI-based connectivity mouse, which specific ASD-relevant mutations can be isolated modeled minimizing environmental contributions. By performing brain-wide mapping across 16 mouse mutants, show that different ASD-associated etiologies cause broad spectrum connectional diverse, often diverging, signatures are recognizable. Despite identified alterations could classified into four subtypes discrete network dysfunction. Our findings variability key determinant heterogeneity ASD, hence reconciling conflicting clinical populations. The identification etiologically-relevant improve diagnostic label accuracy non-syndromic population paves way for personalized treatment approaches.

Language: Английский

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An expanding manifold in transmodal regions characterizes adolescent reconfiguration of structural connectome organization

eLife, Journal Year: 2021, Volume and Issue: 10

Published: March 31, 2021

Adolescence is a critical time for the continued maturation of brain networks. Here, we assessed structural connectome development in large longitudinal sample ranging from childhood to young adulthood. By projecting high-dimensional connectomes into compact manifold spaces, identified marked expansion connectomes, with strongest effects transmodal regions during adolescence. Findings reflected increased within-module connectivity together segregation, indicating increasing differentiation higher-order association networks rest brain. Projection subcortico-cortical patterns these manifolds showed parallel alterations pathways centered on caudate and thalamus. Connectome findings were contextualized via spatial transcriptome analysis, highlighting genes enriched cortex, thalamus, striatum. Statistical learning cortical subcortical features at baseline their maturational change predicted measures intelligence follow-up. Our demonstrate that can bridge conceptual empirical gaps between macroscale network reconfigurations, microscale processes, cognitive outcomes adolescent development.

Language: Английский

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