Recovery of auditory evoked response attentional gain modulation following the first psychotic episode indexes improvements in symptom severity

Attentional control of auditory N100/M100 gain is reduced in individuals with first-episode psychosis (FEP). Persistent problems with executive modulation of auditory sensory activity may impact multiple aspects of psychosis. As a follow-up to our prior work reporting deficits in attentional M100 gain modulation in auditory cortex, we examined changes in M100 gain modulation longitudinally, and further examined relationships between auditory M100 and symptoms of psychosis. We compared auditory M100 in auditory sensory cortex between 21 FEP and 29 matched healthy participants and between timepoints separated by 220 +/- 100 days. Magnetoencephalography data were recorded while participants alternately attended or ignored tones in an auditory oddball task. M100 was measured as the average of 80-140 ms post-stimulus in source-localized evoked responses within bilateral auditory cortex. Symptoms were assessed using the PANSS and PSYRATS. M100 amplitudes, attentional modulation of M100 amplitudes, and symptom severity all improved in FEP over time. Further, improvement in M100 modulation correlated with improvements in negative symptoms (PANSS) as well as physical, cognitive, and emotional components of hallucinations (PSYRATS). Conversely, improvements in the overall size of the M100, rather than the difference between active and passive M100 amplitudes, were related to worsening of positive symptoms (PANSS) and physical components of hallucinations. Results indicate a link between symptoms (particularly auditory hallucinations) and auditory cortex neurophysiology in FEP, where auditory attention and auditory sensation have opposed relationships to symptom change. These findings may inform current models of psychosis etiology and could provide nonpharmaceutical avenues for early intervention.