Journal
CEREBRAL CORTEX
Volume 30, Issue 9, Pages 4922-4937Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhaa084
Keywords
DREADD; excitation: inhibition balance; fMRI; functional connectivity; hypoconnectivity
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Funding
- ETH Research [ETH-38 16-2]
- ETH Career Seed [SEED-42 54 16-1]
- SNSF AMBIZIONE [PZ00P3_173984/1]
- European Research Council (ERC Advanced) (grant BRAINCOMPATH [670 757]
- Swiss National Science Foundation (SNF) [PZ00P3_173984] Funding Source: Swiss National Science Foundation (SNF)
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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 Fmr1 (y/-) 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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