TMS-EEG in the Investigation of Excitation-Inhibition Imbalance in Psychosis and Cognition

AIMS: Transcranial Magnetic Stimulation (TMS) is an in-vivo, non-invasive, and safe method that probes neurophysiological properties associated with cortical glutamatergic (excitatory) and GABAergic (inhibitory) neurotransmission. The combination of TMS with Electroencephalography (EEG) allows us to measure TMS-evoked cortical responses directly from brain activity and it is uniquely placed to elucidate in-vivo cortical Excitatory/Inhibitory processes. Schizophrenia has been associated with Excitation/Inhibition (E/I) imbalance. Cognitive impairment, which is almost ubiquitous in schizophrenia, has been linked with the E/I abnormalities observed in schizophrenia. Among the TMS-EEG evoked potentials (TEPs), the N100 is thought to reflect activation of inhibitory GABA-B cortical circuits and has been associated with attentional processes in healthy individuals, attention deficit hyperactivity disorder (ADHD) and depression. Our aim was to investigate the cortical processes related to the generation of N100 after motor cortex stimulation and its association with attention measures in patients with schizophrenia and healthy controls. METHODS: TEPs were recorded following application of 150 TMS pulses at 90% of resting motor threshold on two brain sites, i.e., left primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC) in stable patients with schizophrenia (n = 9) and healthy controls (n = 9). Region of Interest (ROI) analysis was performed to calculate the regional average of the N100 peak amplitude in M1 and DLPFC based on previous literature. Attention was assessed with a Continuous Performance Task (CPT). RESULTS: We found a significant negative correlation between the amplitude of N100 from M1 and CPT score in the patient group (rho = -0.73, p = 0.026). The N100 component from DLPFC in patients did not correlate with the CPT score (rho = -0.034, p = 0.93), which may suggest regional specificity of M1 inhibitory processes in attention in patients with schizophrenia. CONCLUSION: N100 is considered to be related to cortical inhibitory processes influenced by cortico–striato–thalamo–cortical loops, with greater cortical inhibitory activity producing a larger N100 amplitude. Our preliminary results suggest association of the GABA-B-ergic TEP N100 with attentional processes in M1 and may represent cortical inhibition beyond motor inhibition in patients with schizophrenia. Overall, TMS-EEG offers the potential to investigate the state and dynamics of E/I imbalance in schizophrenia and cognition.