Optimizing Cognitive Remediation

Performance on MATRICS Consensus Cognitive Battery at Baseline Visit as measured by the Global Composite T-score (MCCB-C). The MCCB Global Composite T-score (MCCB-C) is the primary neurocognitive outcome measured at baseline. The MATRICS Consensus Cognitive Battery (MCCB) composite T-score has no minimum or maximum score because it uses T-scores, which are standardized based on a community sample. A normal range MCCB composite T-score is between 40 and 60 and higher scores indicate better neurocognitive outcome. An MCCB composite T-score of 50 represents population mean with a standard deviation of 10.

Performance on a 1-hour computerized auditory cognitive training exercise as measured by the number of levels completed at the baseline visit. Participants were presented with pairs of frequency-modulated sound "sweeps" and indicated whether they perceived each sweep as becoming higher or lower in pitch. A correct response consisted of accurately identifying the trajectory of both sweeps in the stimulus pair. Sweep duration, frequency range, and interstimulus interval (ISI) become shorter after correct responses, but longer after incorrect responses. Participants progressed through repetition of "levels" of ATCT. Each level consisted of identifying 34 sets of stimuli pairs and each level was completed 3 times, before progressing to the next level. Higher values indicate the subject reliably advanced through more levels of the exercise (i.e., became proficient on trials with shorter frequency-modulated sweep durations), while lower values indicate remaining at easier training levels.

Function was assessed via the World Health Organization Disability Schedule 2.0 (WHODAS 2.0) at baseline, and at the 1, 2 and 3 month follow-up visits. The WHODAS 2.0 has a range 12-60, with higher scores indicating worse outcome.

The World Health Organization Quality-of-Life Scale (WHOQOL-BREF) is a 26-item instrument consisting of 4 domains: physical health, psychological health, social relationships and environment. Each item is rated between 1 (not at all) to 5 (completely). The total score is presented between 26 and 156, where higher scores represent higher (better) quality of life. The WHOQOL-BREF was administered at baseline, and at the 1, 2 and 3 month follow-up visits.

The investigators will measure treatment engagement by calculating the proportion of missed and cancelled visits over the course of the study.

Mismatch Negativity (MMN) is an automatic, pre-attentive event-related brain potential (ERP) occurring ~100-250 ms after a deviant stimulus breaks a repetitive pattern of standard stimuli. It reflects sensory memory comparison in the auditory cortex and is a key indicator of perceptual accuracy and neural dysfunction. The MMN is the difference wave obtained by subtracting the ERP response of a standard stimulus from a deviant stimulus. MMN amplitudes generally range from -1 to -5 μV and more negative values reflect better perceptual processing. MMN is assessed only during the baseline visit.