Enhancing Neuroplasticity to Augment Cognitive Remediation in Schizophrenia

Abstract

There is a burgeoning need for innovative treatment strategies to improve the cognitive deficits in schizophrenia. Cognitive remediation (CR) is effective at the group level, but the variability in treatment response is large. Given that CR may depend on intact neuroplasticity to produce cognitive gains, it is reasonable to combine it with strategies that harness patients’ neuroplastic potential. In this review, we discuss two non-pharmacological approaches that can enhance neuroplasticity and possibly augment the effects of CR in schizophrenia: physical exercise and transcranial direct current stimulation (tDCS). Substantial body of evidence supports the beneficial effect of physical exercise on cognition, and a handful of studies in schizophrenia have shown that physical exercise in conjunction with CR has a larger impact on cognition than CR alone. Physical exercise is thought to stimulate neuroplasticity through the regulation of central growth factors, and current evidence points to brain-derived neurotrophic factor as the potential underlying mechanism through which physical exercise might enhance the effectiveness of CR. tDCS has emerged as a potential tool for cognitive enhancement and seems to affect the cellular mechanisms involved in long-term potentiation (LTP). A few reports have demonstrated the feasibility of integrating tDCS with CR in schizophrenia, but there are insufficient data to determine if this multimodal approach leads to incremental performance gain in patients. Larger randomized controlled trials are necessary to understand the mechanisms of the combined tDCS–CR intervention. Future research should take advantage of new developments in neuroplasticity paradigms to examine the effects of these interventions on LTP.

Current understandings of the trajectory and emerging correlates of cognitive impairment in bipolar disorder: An overview of evidence

“…Recent work in SZ patients showed that supported physical exercise training resulted in moderate improvements in several domains of cognition across a 12 week period . Converging evidence suggests that physical activity can enhance neuroplasticity by regulating growth factors such as BDNF, which may augment treatments directly training cognition . Thus, it is possible that the pro‐cognitive effects of exercise therapy can extend to BD, and we anticipate that multimodal interventions targeting modifiable lifestyle risk factors such as exercise, sleep and diet alongside cognitive training, might be one of the most powerful means by which to enhance cognitive functioning in the illness.…”

Thinking While Moving or Moving While Thinking – Concepts of Motor-Cognitive Training for Cognitive Performance Enhancement

“…BDNF is associated with synaptogenesis and neurogenesis which may foster improved cognition ( Cotman et al, 2007 ; Lu et al, 2013 ; Brigadski and Leßmann, 2014 ; Borror, 2017 ). Notably, an increased level of BDNF was observed during physical exercises and up to 60 min after cessation of the acute bout of physical exercises ( Knaepen et al, 2010 ; Piepmeier and Etnier, 2015 ; Dinoff et al, 2017 ). Based on this observation, the “facilitation effects” of acute physical exercises seem transient and time-constrained ( Fissler et al, 2013 ).…”

Nonsocial and social cognition in schizophrenia: current evidence and future directions

“…A recent meta‐analysis has shown that physical exercise can improve cognition in schizophrenia compared to non‐aerobic control activities. These encouraging findings have led to a few small pilot studies which found that the combination of cognitive remediation plus aerobic exercise leads to differential improvement for some aspects of cognition and functioning. Similarly, based on findings that transcranial direct current stimulation (tDCS) may improve selected aspects of cognition in schizophrenia, a few small pilot studies have reported differential benefits of brief cognitive remediation plus tDCS (versus sham) interventions on trained cognitive tasks.…”

“…Aside from oxytocin, studies have started to examine the possibility of improving social cognition in schizophrenia through physical exercise and neurostimulation with tDCS. Only a few studies have examined the effects of exercise, providing early encouraging results (g=0.71, based on three studies). An initial study by our team found that a single session of tDCS (vs. sham), administered over the prefrontal cortex, significantly improved facial identification task performance, though not other social cognitive domains.…”