Connectome-based modelling reveals ketamine's modulatory effects on thalamocortical connectivity during auditory attention processing

Poster Session A - Saturday, April 13, 2024, 2:30 – 4:30 pm EDT, Sheraton Hall ABC

Andreea Diaconescu^1,2 (andreea.diaconescu@camh.ca), Zheng Wang¹, Milad Soltanzadeh^1,2, Davide Momi¹, Andrew Clappison³, Andre Schmidt⁴, Franz Vollenweider⁵, John D Griffiths^1,2; ¹University of Toronto, ²Centre for Addiction and Mental Health, ³University of Ottawa, ⁴Unversity of Basel, ⁵University Hospital of Psychiatry, Zurich

This study investigates the impact of ketamine, an NMDA receptor antagonist and pharmacological model for schizophrenia, on brain dynamics during sensory learning. Using EEG data from a placebo-controlled, crossover design study, we analyze auditory mismatch negativity (MMN) brain responses using a connectome-based neural mass modelling framework, focusing on the physiology of cortico-striato-thalamo-cortical (CSTC) circuits. Auditory responses are introduced to the network via auditory cortex regions, and EEG signals are generated from regional neural activity using a leadfield matrix. The model is implemented within the Whole-Brain Modelling in PyTorch (WhoBPyT) library (github.com/griffithslab/whobpyt), allowing simulation and automatic differentiation-based estimation of neurophysiological model parameters. We focus here on parameters describing connection strengths both within the cortex and across the CSTC circuit, comparing ketamine’s effects against placebo during the oddball task. Partial least squares analysis revealed significant differences between ketamine and placebo conditions in standard and deviant tone responses. Analysis of fitted model parameters showed greater connection gains from pyramidal-to-inhibitory populations and thalamus-to-D1 connection gains in the placebo condition, indicating more pronounced inhibition within nodes and stronger thalamic inhibition across nodes compared to the ketamine condition. Additionally, under ketamine, increased D2 connection gains were observed in specific brain regions, along with altered thalamocortical connectivity patterns. These results highlight substantial changes in brain connectivity patterns under ketamine, particularly in thalamus to D1 and cortex to D2 connections. These findings provide insights into the neural mechanisms of schizophrenia spectrum disorders, emphasizing the significant alterations in neural pathways induced by ketamine, affecting cortical intra-connections and thalamocortical interactions.

Topic Area: ATTENTION: Auditory