Intensive cognitive training in schizophrenia enhances working memory and associated prefrontal cortical efficiency in a manner that drives long-term functional gains

Abstract

We investigated whether intensive computerized cognitive training in schizophrenia could improve working memory performance and increase signal efficiency of associated middle frontal gyri (MFG) circuits in a functionally meaningful manner. Thirty schizophrenia participants and 13 healthy comparison participants underwent fMRI scanning during a letter N-back working memory task. Schizophrenia participants were then randomly assigned to either 80 hours (16 weeks) of cognitive training or a computer games control condition. After this intervention, participants completed a second fMRI N-back scanning session. At baseline, during 2-back working memory trials, healthy participants showed the largest and most significant activation in bilateral MFG, which correlated with task performance. Schizophrenia participants showed impaired working memory, hypoactivation in left MFG, and no correlation between bilateral MFG signal and task performance. After training, schizophrenia participants improved their 2-back working memory performance and showed increased activation in left MFG. They also demonstrated a significant association between enhanced task performance and right MFG signal, similar to healthy participants. Both task performance and brain activity in right MFG after training predicted better generalized working memory at 6-month follow-up. Furthermore, task performance and brain activity within bilateral MFG predicted better occupational functioning at 6-month follow-up. No such findings were observed in the computer games control participants. Working memory impairments in schizophrenia and its underlying neural correlates in MFG can be improved by intensive computerized cognitive training; these improvements generalize beyond the trained task and are associated with enduring effects on cognition and functioning 6 months after the intervention.

Cluster analysis differentiates high and low community functioning in schizophrenia: Subgroups differ on working memory but not other neurocognitive domains

“…In addition, CRT has been associated with improvements in other aspects of community functioning, including social adjustment and psychosocial functioning (Harvey and Bowie, 2012b;Medalia and Saperstein, 2013;Wykes et al, 2011). Our findings are also consistent with two recent studies that found enhanced working memory following cognitive training was associated with better occupational functioning (Subramaniam et al, 2014) and that verbal working memory was the strongest predictor of employment status (Kaneda et al, 2009). Overall, the CRT literature suggests that working memory is a viable treatment target and critical for community functioning.…”

Converging effects of diverse treatment modalities on frontal cortex in schizophrenia: A review of longitudinal functional magnetic resonance imaging studies

“…Three of these used N-back tasks to assess WM (64-66), one used an N-back task and a lexical task together (67), and another used a verbal memory task (68). …”

Social impairment in schizophrenia

“…These characteristics promote motivation and elicit neuromodulators, such as dopamine and acetylcholine, which enhance the molecular basis of learning (e.g., synaptic plasticity) [21,22]. Cognitive training programs that incorporate these principles produce neural changes that are associated with behavioral improvements in cognition (including social cognition) and day-to-day functioning for healthy individuals [17,18], people with schizophrenia [19,**23], and people at risk for schizophrenia [**24]. …”

“…These include regions primarily involved in emotion processing – amygdala, somatosensory-related cortex (SRC), ventral striatum, and medial orbitofrontal cortex (MOFC); cognitive control (used in self-regulatory processes) – lateral prefrontal cortex (LPFC), anterior cingulate cortex (ACC), and superior parietal lobe; and theory of mind – superior temporal sulcus (STS), temporoparietal junction (TPJ), posterior cingulate, and medial prefrontal cortex (MPFC) [9]; 2) Schizophrenia is associated with neural dysfunction in these regions, and the degree of dysfunction is related to social cognitive performance and real-world social behavior [*10,11]; and 3) Cognitive deficits related to neural dysfunction in schizophrenia can be improved through behavioral interventions, such as computer-based cognitive training, that promote neuroplasticity. More specifically, intense behavioral practice of a cognitive skill (e.g., working-memory), improves the underlying neural system supporting that skill, and learning-induced neural changes are related to better cognitive performance [**12,13–19]. These data indicate that neuroplasticity-based approaches could improve social impairment in schizophrenia.…”