Mismatch negativity reveals plasticity in cortical dynamics after 1-hour of auditory training exercises.

BACKGROUND: Impaired sensory processing contributes to deficits in cognitive and psychosocial functioning in individuals with schizophrenia (SZ). Mismatch Negativity (MMN), an event-related potential (ERP) index of sensory discrimination associated with cognitive and psychosocial functioning, is a candidate biomarker of auditory discrimination and thus possibly of changes following auditory-based Targeted Cognitive Training (TCT). Here we evaluated the acute effect of TCT on cortical processes supporting auditory discrimination. METHODS: MMN was assessed in 28 SZ outpatients before and after a single 1-hour (hr) session of "Sound Sweeps," a pitch discrimination task that is a component of the TCT suite of exercises. Independent component (IC) analysis was applied to decompose 64-channel scalp-recorded electroencephalogram (EEG) activity into spatiotemporally stationary sources and their activities. ICs from all patients were pooled to find commonalities in their cortical locations. IC cluster-mean ERPs were evaluated to determine the clusters contributing to the (140-200 ms) MMN difference between responses to deviant and standard tone stimuli respectively. RESULTS: Two frontal IC clusters centered in orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC) accounted for >77% of MMN variance across all scalp channels. After 1-hr auditory training, significant suppression of ACC cluster contributions was detected, whereas the OFC cluster contribution was unchanged. CONCLUSIONS: Prior to TCT, the MMN response was dominated by EEG effective sources in or near OFC and ACC. However, after 1-hr of auditory-based TCT, a significant attenuation of ACC was observed, whereas OFC contribution to MMN persisted. The present findings support further trials designed to test whether training-related MMN plasticity in the ACC after 1-hr may predict individual patient response to a full course of TCT.

Mismatch Negativity is a Sensitive and Predictive Biomarker of Perceptual Learning During Auditory Cognitive Training in Schizophrenia.

Computerized cognitive training is gaining empirical support for use in the treatment of schizophrenia (SZ). Although cognitive training is efficacious for SZ at a group level when delivered in sufficiently intensive doses (eg, 30-50 h), there is variability in individual patient response. The identification of biomarkers sensitive to the neural systems engaged by cognitive training interventions early in the course of treatment could facilitate personalized assignment to treatment. This proof-of-concept study was conducted to determine whether mismatch negativity (MMN), an event-related potential index of auditory sensory discrimination associated with cognitive and psychosocial functioning, would predict gains in auditory perceptual learning and exhibit malleability after initial exposure to the early stages of auditory cognitive training in SZ. MMN was assessed in N=28 SZ patients immediately before and after completing 1 h of a speeded time-order judgment task of two successive frequency-modulated sweeps (Posit Science 'Sound Sweeps' exercise). All SZ patients exhibited the expected improvements in auditory perceptual learning over the 1 h training period (p<0.001), consistent with previous results. Larger MMN amplitudes recorded both before and after the training exercises were associated with greater gains in auditory perceptual learning (r=-0.5 and r=-0.67, respectively, p's<0.01). Significant pretraining vs posttraining MMN amplitude reduction was also observed (p<0.02). MMN is a sensitive index of the neural systems engaged in a single session of auditory cognitive training in SZ. These findings encourage future trials of MMN as a biomarker for individual assignment, prediction, and/or monitoring of patient response to procognitive interventions, including auditory cognitive training in SZ.