Adjusting Brain Dynamics in Schizophrenia by Means of Perceptual and Cognitive Training

Abstract

BackgroundIn a previous report we showed that cognitive training fostering auditory-verbal discrimination and working memory normalized magnetoencephalographic (MEG) M50 gating ratio in schizophrenia patients. The present analysis addressed whether training effects on M50 ratio and task performance are mediated by changes in brain oscillatory activity. Such evidence should improve understanding of the role of oscillatory activity in phenomena such as M50 ratio, the role of dysfunctional oscillatory activity in processing abnormalities in schizophrenia, and mechanisms of action of cognitive training.Methodology/Principal FindingsTime-locked and non-time-locked oscillatory activity was measured together with M50 ratio in a paired-click design before and after a 4-week training of 36 patients randomly assigned to specific cognitive exercises (CE) or standard (comparison) cognitive training (CP). Patient data were compared to those of 15 healthy controls who participated in two MEG measurements 4 weeks apart without training. Training led to more time-locked gamma-band response and more non-time-locked alpha-band desynchronization, moreso after CE than after CP. Only after CE, increased alpha desynchronization was associated with normalized M50 ratio and with improved verbal memory performance. Thus, both types of cognitive training normalized gamma activity, associated with improved stimulus encoding. More targeted training of auditory-verbal discrimination and memory additionally normalized alpha desynchronization, associated with improved elaborative processing. The latter presumably contributes to improved auditory gating and cognitive function.Conclusions/SignificanceResults suggest that dysfunctional interplay of ocillatory activity that may contribute to auditory processing disruption in schizophrenia can be modified by targeted training.

Measuring the capacity for auditory system plasticity: An examination of performance gains during initial exposure to auditory-targeted cognitive training in schizophrenia

“…Specifically, the degree of APS improvement occurring after one hour of exposure to auditory frequency discrimination training may indicate the degree to which adaptive tuning has taken place within temporal cortex; the positive association we observed between baseline verbal memory scores and APS improvement suggests that this tuning may be greater (or may occur more rapidly) in patients with relatively strong verbal memory abilities prior to training. Taken in context with previous research showing a positive relationship between APS improvements and cognitive enhancement (Fisher et al, 2015; Murthy et al, 2012; Popov et al, 2011; 2012; 2015), our results further suggest that patients with relatively intact verbal memory performance at baseline may ultimately be shown to respond better to ATCT than might patients with relative verbal memory impairments. This assertion makes intuitive sense, given that the learning and memory capabilities indexed by measures like the CVLT-II presumably engage similar neuroplastic mechanisms to those engaged by ATCT (e.g.…”

“…Auditory perceptual improvements (i.e. auditory “tuning”) gained during treatment may be a key predictor of ATCT response, as they have been shown to correspond to overall degree of cognitive enhancement (Murthy et al, 2012; Popov et al, 2011; 2012; 2015). Notably, Fisher et al (2015) found that auditory processing speed improvements after 20 hours of training correlated with degree of cognitive enhancement after up to 40 hours of training, suggesting that these early auditory processing improvements may reflect the “plasticity potential” of the frontotemporal network and thus index the likelihood of cognitive benefit from ATCT.…”

Searching for Cross-Diagnostic Convergence: Neural Mechanisms Governing Excitation and Inhibition Balance in Schizophrenia and Autism Spectrum Disorders

“…By pairing drug trials with bench work to understand specific targets and action mechanisms for successful pharmacological agents, we stand to learn more about both treatment and underlying dysfunction. Interestingly, recent work suggests that cognitive training can normalize neural markers of altered auditory gating in SCZ, suggesting non-pharmacological interventions may also be successful in modulating and normalizing neural responses associated with cortical disinhibition(142). …”

Neuroimaging Biomarkers for Early Drug Development in Schizophrenia

“…Using repeated administration of transcranial magnetic stimulation (TMS), Farzan et al (65) repressed “excessive” gamma power in the dorsolateral prefrontal cortex in patients during a working m emory task,an effect associated with improved task performance. Using cognitive exercises (auditory processing/working memory “training”), Popov et al observed increased time-locked, auditory stimulus-evoked gamma power as well as improved verbal memory in patients (66). …”