Decrease in gamma-band auditory steady-state response in patients with treatment-resistant schizophrenia.

BACKGROUND: Thirty percent of patients with schizophrenia do not respond to non-clozapine antipsychotics and are termed treatment-resistant schizophrenia (TRS). The 40-Hz auditory steady-state response (ASSR) is a well-known to be reduced in patients with schizophrenia compared to healthy controls (HCs), suggesting impaired gamma oscillation in schizophrenia. Given no ASSR study on TRS, we aimed to examine the neurophysiological basis of TRS employing 40-Hz ASSR paradigm. METHOD: We compared ASSR measures among HCs, patients with non-TRS, and patients with TRS. TRS criteria were defined by a score of 4 or higher on two items of the Positive and Negative Syndrome Scale (PANSS) positive symptoms despite standard antipsychotic treatment. Participants were examined for ASSR with 40-Hz click-train stimulus, and then time-frequency analysis was performed to calculate evoked power and phase-locking factor (PLF) of 40-Hz ASSR. RESULTS: A total of 79 participants were included: 27 patients with TRS (PANSS = 92.6 ± 15.8); 27 patients with non-TRS (PANSS = 63.3 ± 14.7); and 25 HCs. Evoked power in 40-Hz ASSR was lower in the TRS group than in the HC group (F2,79 = 8.37, p = 0.015; TRS vs. HCs: p = 0.012, d = 1.1) while no differences in PLF were found between the groups. CONCLUSION: These results suggest that glutamatergic and GABAergic neurophysiological dysfunctions are involved in the pathophysiology of TRS. Our findings warrant more comprehensive and longitudinal studies for deep phenotyping of TRS.

Motor cortex excitability and inhibitory imbalance in autism spectrum disorder assessed with transcranial magnetic stimulation: a systematic review.

Cortical excitation/inhibition (E/I) imbalances contribute to various clinical symptoms observed in autism spectrum disorder (ASD). However, the detailed pathophysiologic underpinning of E/I imbalance remains uncertain. Transcranial magnetic stimulation (TMS) motor-evoked potentials (MEP) are a non-invasive tool for examining cortical inhibition in ASD. Here, we conducted a systematic review on TMS neurophysiology in motor cortex (M1) such as MEPs and short-interval intracortical inhibition (SICI) between individuals with ASD and controls. Out of 538 initial records, we identified six articles. Five studies measured MEP, where four studies measured SICI. There were no differences in MEP amplitudes between the two groups, whereas SICI was likely to be reduced in individuals with ASD compared with controls. Notably, SICI largely reflects GABA(A) receptor-mediated function. Conversely, other magnetic resonance spectroscopy and postmortem methodologies assess GABA levels. The present review demonstrated that there may be neurophysiological deficits in GABA receptor-mediated function in ASD. In conclusion, reduced GABAergic function in the neural circuits could underlie the E/I imbalance in ASD, which may be related to the pathophysiology of clinical symptoms of ASD. Therefore, a novel treatment that targets the neural circuits related to GABA(A) receptor-mediated function in regions involved in the pathophysiology of ASD may be promising.