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STXBP1 Syndrome Is Characterized by Inhibition-Dominated Dynamics of Resting-State EEG.

ABSTRACT: STXBP1 syndrome is a rare neurodevelopmental disorder caused by heterozygous variants in the STXBP1 gene and is characterized by psychomotor delay, early-onset developmental delay, and epileptic encephalopathy. Pathogenic STXBP1 variants are thought to alter excitation-inhibition (E/I) balance at the synaptic level, which could impact neuronal network dynamics; however, this has not been investigated yet. Here, we present the first EEG study of patients with STXBP1 syndrome to quantify the impact of the synaptic E/I dysregulation on ongoing brain activity. We used high-frequency-resolution analyses of classical and recently developed methods known to be sensitive to E/I balance. EEG was recorded during eyes-open rest in children with STXBP1 syndrome (n = 14) and age-matched typically developing children (n = 50). Brain-wide abnormalities were observed in each of the four resting-state measures assessed here: (i) slowing of activity and increased low-frequency power in the range 1.75-4.63 Hz, (ii) increased long-range temporal correlations in the 11-18 Hz range, (iii) a decrease of our recently introduced measure of functional E/I ratio in a similar frequency range (12-24 Hz), and (iv) a larger exponent of the 1/f-like aperiodic component of the power spectrum. Overall, these findings indicate that large-scale brain activity in STXBP1 syndrome exhibits inhibition-dominated dynamics, which may be compensatory to counteract local circuitry imbalances expected to shift E/I balance toward excitation, as observed in preclinical models. We argue that quantitative EEG investigations in STXBP1 and other neurodevelopmental disorders are a crucial step to understand large-scale functional consequences of synaptic E/I perturbations.

SUBMITTER: Houtman SJ

PROVIDER: S-EPMC8733612 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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STXBP1 Syndrome Is Characterized by Inhibition-Dominated Dynamics of Resting-State EEG.

Houtman Simon J SJ Lammertse Hanna C A HCA van Berkel Annemiek A AA Balagura Ganna G Gardella Elena E Ramautar Jennifer R JR Reale Chiara C Møller Rikke S RS Zara Federico F Striano Pasquale P Misra-Isrie Mala M van Haelst Mieke M MM Engelen Marc M van Zuijen Titia L TL Mansvelder Huibert D HD Verhage Matthijs M Bruining Hilgo H Linkenkaer-Hansen Klaus K

Frontiers in physiology 20211223

STXBP1 syndrome is a rare neurodevelopmental disorder caused by heterozygous variants in the STXBP1 gene and is characterized by psychomotor delay, early-onset developmental delay, and epileptic encephalopathy. Pathogenic STXBP1 variants are thought to alter excitation-inhibition (E/I) balance at the synaptic level, which could impact neuronal network dynamics; however, this has not been investigated yet. Here, we present the first EEG study of patients with STXBP1 sy ...[more]

PMID: 35002760

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Project description:Functional and effective connectivity are known to change systematically over time. These changes might be explained by several factors, including intrinsic fluctuations in activity-dependent neuronal coupling and contextual factors, like experimental condition and time. Furthermore, contextual effects may be subject-specific or conserved over subjects. To characterize fluctuations in effective connectivity, we used dynamic causal modelling (DCM) of cross spectral responses over 1- min of electroencephalogram (EEG) recordings during rest, divided into 1-sec windows. We focused on two intrinsic networks: the default mode and the saliency network. DCM was applied to estimate connectivity in each time-window for both networks. Fluctuations in DCM connectivity parameters were assessed using hierarchical parametric empirical Bayes (PEB). Within-subject, between-window effects were modelled with a second-level linear model with temporal basis functions as regressors. This procedure was conducted for every subject separately. Bayesian model reduction was then used to assess which (combination of) temporal basis functions best explain dynamic connectivity over windows. A third (between-subject) level model was used to infer which dynamic connectivity parameters are conserved over subjects. Our results indicate that connectivity fluctuations in the default mode network and to a lesser extent the saliency network comprised both subject-specific components and a common component. For both networks, connections to higher order regions appear to monotonically increase during the 1- min period. These results not only establish the predictive validity of dynamic connectivity estimates - in virtue of detecting systematic changes over subjects - they also suggest a network-specific dissociation in the relative contribution of fluctuations in connectivity that depend upon experimental context. We envisage these procedures could be useful for characterizing brain state transitions that may be explained by their cognitive or neuropathological underpinnings.

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STXBP1 Syndrome Is Characterized by Inhibition-Dominated Dynamics of Resting-State EEG.

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<i>STXBP1</i> Syndrome Is Characterized by Inhibition-Dominated Dynamics of Resting-State EEG.

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