Cortical Excitation:Inhibition Imbalance Causes Abnormal Brain Network Dynamics as Observed in Neurodevelopmental Disorders
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Date
2020-09
Publication Type
Journal Article
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yes
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Abstract
Abnormal brain development manifests itself at different spatial scales. However, whether abnormalities at the cellular level can be diagnosed from network activity measured with functional magnetic resonance imaging (fMRI) is largely unknown, yet of high clinical relevance. Here a putative mechanism reported in neurodevelopmental disorders, that is, excitation-to-inhibition ratio (E:I), was chemogenetically increased within cortical microcircuits of the mouse brain and measured via fMRI. Increased E:I caused a significant “reduction” of long-range connectivity, irrespective of whether excitatory neurons were facilitated or inhibitory Parvalbumin (PV) interneurons were suppressed. Training a classifier on fMRI signals, we were able to accurately classify cortical areas exhibiting increased E:I. This classifier was validated in an independent cohort of Fmr1y/− knockout mice, a model for autism with well-documented loss of parvalbumin neurons and chronic alterations of E:I. Our findings demonstrate a promising novel approach towards inferring microcircuit abnormalities from macroscopic fMRI measurements.
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published
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Journal / series
Volume
30 (9)
Pages / Article No.
4922 - 4937
Publisher
Oxford University Press
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Edition / version
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Date created
Subject
DREADD; Excitation; Inhibition balance; fMRI; Functional connectivity; Hypoconnectivity
Organisational unit
03963 - Wenderoth, Nicole / Wenderoth, Nicole
Notes
Funding
173984 - Pharmacogenetic fMRI in brain circuits underlying social motivation and repetitive behavior (SNF)