S52. MODULATING EXECUTIVE FUNCTIONS IN SCHIZOPHRENIA: TRANSLATIONAL APPLICATIONS FROM CLINICAL COGNITIVE NEUROSCIENCE

Abstract

Background Cognitive dysfunction is a core symptom of schizophrenia-spectrum illnesses that the field still struggles to treat. There is a limited treatment response from pharmacologic and psychotherapeutic intervention with what are frequently debilitating cognitive symptoms. Transcranial direct current stimulation is a form of noninvasive brain stimulation using low-intensity electrical currents that aim to modulate brain regions and networks. The mechanism of action is a change in membrane potentials in the cortex, with the intention of inducing neuroplastic change through modulation and rehabilitation of aberrant function or enhancement in healthy individuals. Methods A literature search was conducted on the PubMed/NCBI Database. This meta-analysis uses the more flexible Hedge's g effect size. Sham-adjusted effect sizes will be reported and confidence intervals provide an overall measure of the effects' variability. Results Working memory and attentional processes improved in some, but not all studies of tDCS in schizophrenia that were targeting executive function. This finding is encouraging regarding applied clinical cognitive neuroscience, echoing the findings of past reviews (e.g. Mervis et al. 2017) in the context of a need for more tDCS studies in schizophrenia (e.g. Philip et al. 2017). There seems to be converging evidence for working memory improvement across study designs, behavioral and neurophysiologic measures, and sample sizes. Attention-related constructs are also well studied and show improvements, though are far less homogeneous than working memory in their measures and include attentive and pre-attentive processes. Executive functions that are harder to put into categories (e.g. verbal learning, problem-solving) also showed improvements. Discussion If cognitive dysfunction is a core attribute of schizophrenia that can reasonably merit inclusion as disease criteria (Keefe, 2008), it merits broader acknowledgment as a valid treatment target. Multiple other meta-analyses highlighted aspects of disturbed executive function in schizophrenia across the disease course, even though there is some disagreement about when they show up and if they predict conversion from risk states. Based on the general nature of the tDCS-induced electric fields, looking to network dysfunction and specific brain regions may be a sensible method for seeking a mechanism of executive function improvement. The current findings with enhanced cognitive function point to dopamine and glutamate in tDCS's effects in schizophrenia. A number of studies in basic neuroscience research show that tDCS appears to induce plasticity via glutamate, which is nonlinearly modulated by dopamine. Both neurotransmitters and their constituent receptors are studied extensively in schizophrenia and are common subjects of biological hypotheses of etiology and function. This involvement of glutamate and dopamine in tDCS-induced plasticity suggests an important potential role in treatment of schizophrenia with applied clinical neuroscience techniques. Thalamocortical connectivity is another natural target of translational research pursuits in applied clinical cognitive neuroscience. In light of the findings on working memory and attentional processes improving, thalamocortical connectivity provides a unifying framework for sensory processes and higher cognitive functions. Researchers found evidence for prefrontal dysfunction and prefrontal-thalamocortical dysconnectivity that corresponds to executively-oriented cognitive symptoms and may be specifically dysfunctional in schizophrenia.