Journal
BRAIN CONNECTIVITY
Volume 9, Issue 3, Pages 263-272Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/brain.2018.0639
Keywords
ASD; cross-frequency coupling; gamma; phase; phase-amplitude coupling
Categories
Funding
- Autism Science Foundation [ASF 13-1007]
- National Institutes of Health [5T32MH019112-27, K01MH096091, R21MH110869, R01DC 008871, U54HD HD086984, 1P50MH096891]
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Altered gamma-band electrophysiological activity in individuals with autism spectrum disorder (ASD) is well documented, and analogous gamma-band alterations are recapitulated in several preclinical murine models relevant to ASD. Such gamma-band activity is hypothesized to underlie local circuit processes. Gamma-band cross-frequency coupling (CFC), a related though distinct metric, interrogates local neural circuit signal integration. Several recent studies have observed perturbed gamma-band CFC in individuals with ASD, although the direction of change remains unresolved. It also remains unclear whether murine models relevant to ASD recapitulate this altered gamma-band CFC. As such, this study examined whether mice with parvalbumin (PV) cell-specific ablation of NMDA-R1 (PVcre/NR1(fl/fl)) demonstrated altered gamma-band CFC as compared with their control littermates (PVcre/NR1(+/+)-mice that do not have the PV cell-specific ablation of NMDA-R1). Ten mice of each genotype had 4 min of resting electroencephalography recorded and analyzed. First, resting electrophysiological power was parsed into the canonical frequency bands and genotype-related differences were subsequently explored so as to provide context for the subsequent CFC analyses. PVcre/NR1(fl/fl) mice exhibited an increase in resting power specific to the high gamma-band, but not other frequency bands, as compared with PVcre/NR1(+/+). CFC analyses then examined both the standard magnitude (strength) of CFC and the novel metric Phase(Max)-which denotes the phase of the lower frequency signal at which the peak higher frequency signal power occurred. PVcre/NR1(fl/fl) mice exhibited altered Phase(Max), but not strength, of gamma-band CFC as compared with PVcre/NR1(+/+) mice. As such, this study suggests a potential novel metric to explore when studying neuropsychiatric disorders.
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