Auditory Cortical Plasticity Drives Training-Induced Cognitive Changes in Schizophrenia

Abstract

Schizophrenia is characterized by dysfunction in basic auditory processing, as well as higher-order operations of verbal learning and executive functions. We investigated whether targeted cognitive training of auditory processing improves neural responses to speech stimuli, and how these changes relate to higher-order cognitive functions. Patients with schizophrenia performed an auditory syllable identification task during magnetoencephalography before and after 50 hours of either targeted cognitive training or a computer games control. Healthy comparison subjects were assessed at baseline and after a 10 week no-contact interval. Prior to training, patients (N = 34) showed reduced M100 response in primary auditory cortex relative to healthy participants (N = 13). At reassessment, only the targeted cognitive training patient group (N = 18) exhibited increased M100 responses. Additionally, this group showed increased induced high gamma band activity within left dorsolateral prefrontal cortex immediately after stimulus presentation, and later in bilateral temporal cortices. Training-related changes in neural activity correlated with changes in executive function scores but not verbal learning and memory. These data suggest that computerized cognitive training that targets auditory and verbal learning operations enhances both sensory responses in auditory cortex as well as engagement of prefrontal regions, as indexed during an auditory processing task with low demands on working memory. This neural circuit enhancement is in turn associated with better executive function but not verbal memory.

Engagement with the auditory processing system during targeted auditory cognitive training mediates changes in cognitive outcomes in individuals with schizophrenia.

“…This finding is consistent with our recent MEG study demonstrating that TCT drives auditory cortical plasticity, which in turn correlates with prefrontal plasticity and generalized cognitive gains (Dale et al, 2015). In addition, our analysis suggests that, while it is necessary for the training target to be engaged (as reflected by a significant initial APS change), it is the APS plateau reached after 20 hours that shows a significant association with the magnitude of generalized cognitive gains.…”

“…Indeed, our emerging magnetoencephalographic data indicate that TCT enhances both early auditory representations in primary auditory cortex as well as both early and later task-related activity in prefrontal sectors (Dale et al, 2010; Dale et al, 2015). …”

Blocking NMDAR Disrupts Spike Timing and Decouples Monkey Prefrontal Circuits: Implications for Activity-Dependent Disconnection in Schizophrenia

“…Consistent with this hypothesis, functional imaging studies in patients have repeatedly shown that schizophrenia weakens functional coupling in prefrontal networks based on reduced temporal correlations in BOLD signal across brain areas (Kang et al, 2011; Kubota et al, 2013; Lawrie et al, 2002; Mitelman et al, 2005; Mukherjee et al, 2016; Scariati et al, 2016; Tu et al, 2012, 2013). Measurements of brain activity at higher temporal resolution using electroencephalograms (EEG) and magnetoencephalography (MEG) have shown reduced synchrony in gamma band during task performance (Dale et al, 2016; Uhlhaas and Singer, 2015). The spike-timing-dependent synaptic disconnection theory is an elaboration of these prior theories extending the synchrony deficits described at larger physical scales within the brain to the level of spiking neurons, considering the impact of spike timing disruption on synaptic connectivity operating through spike-timing-dependent plasticity mechanisms.…”

Gamma band oscillations

“…First, cognitive remediation therapy findings in schizophrenia patients showed that training which targets auditory and verbal learning enhanced sensory response in both the auditory and dorsolateral prefrontal cortex, accompanied by an increase in evoked GBO [89]. This neural circuit enhancement was additionally associated with an increase in executive function.…”