Ketamine and psilocybin differentially modulate the aperiodic component of the power spectral density

Poster Session F - Tuesday, April 16, 2024, 8:00 – 10:00 am EDT, Sheraton Hall ABC

Milad Soltanzadeh^1,2 (milad.soltanzadeh@mail.utoronto.ca), Zheng Wang², Shona G. Allohverdi^1,2, André Schmidt³, Franz X. Vollenweider⁴, Andreea Diaconescu^1,2; ¹University of Toronto, ²Centre for Addiction and Mental Health (CAMH), Toronto, ³University of Basel, ⁴University Hospital of Psychiatry, Zurich

Ketamine and psilocybin are being explored for their potential in studying and treating psychiatric disorders like major depression and schizophrenia. Ketamine, a dissociative hallucinogen, blocks glutamatergic N-methyl-D-aspartate receptors (NMDARs) in the brain, while psilocybin modulates serotonergic 5-HT2A receptors. Similar to schizophrenia's EEG profiles, a single ketamine infusion induces changes in the EEG signal, affecting event-related potential amplitude and activity within the gamma, beta, and alpha frequency bands. In addition to the information encoded in the periodic components, the aperiodic components of the spectrum, notably the 1/f slope, may reflect underlying neuronal dynamics, including excitatory-inhibitory balance. In our analysis of EEG recordings from 19 subjects during an auditory roving mismatch negativity (MMN) paradigm, we assessed changes under ketamine and placebo conditions. We aimed to detect shifts in the excitatory-inhibitory balance through aperiodic components and compare spectral differences between conditions. We used “fitting oscillations and one-over-f (FOOOF)” to model spectral parameters and partial least squares to statistically analyze their distributions. Our results indicate that ketamine significantly affects alpha and beta bands and alters the EEG spectrum's slope in certain brain regions, indicating altered excitatory-inhibitory balance. This effect is unique to ketamine, as psilocybin only decreases alpha power without affecting aperiodic components. In conclusion, our results emphasize a link between the excitatory-inhibitory balance and the spectrum's slope, reinforcing ketamine's utility as a model for psychosis. Our findings suggest that these large-scale biomarkers of the excitatory-inhibitory balance may be used for early schizophrenia diagnosis.

Topic Area: METHODS: Electrophysiology