Neuroscience‐informed computer‐assisted cognitive training in schizophrenia

Abstract

Schizophrenia is a heterogeneous psychiatric syndrome characterized by psychosis. It is also a neurodevelopmental disorder. In the earliest phases of the illness, at-risk individuals exhibit subtle, nonspecific symptoms, including cognitive dysfunction and progressive brain volumetric loss. Generally, schizophrenia is characterized by abnormal/inefficient neural system operations and neural oscillatory activity, as well as functional disconnectivity across frontal-temporo parietal and frontal-subcortical networks; it thus may best be described as a widespread neural oscillatory connectomopathy. Despite earlier views of schizophrenia as an inevitably progressive neurodegenerative disease, emerging evidence indicates that endogenous neuroplastic capacity is retained. An active area of research is directed at understanding how best to harness this learning-induced neuroplasticity to enhance neural system functioning, improve cognition, and prevent-and possibly even reverse-disease progression. In this review, we present an overview of results from the most widely used computer-assisted cognitive-training programs in schizophrenia, contrasting a broad neuropsychological rehabilitation approach with a targeted cognitive-training approach. We then review studies on the neurobiological effects of these two training methods. Finally, we discuss future directions with a focus on the "oscillatory connectome" as a key area of investigation for developing the most precise and scientifically informed treatment approaches for this illness.

Neurophysiologic measures of target engagement predict response to auditory-based cognitive training in treatment refractory schizophrenia

“…[37]), and determine whether this malleability predicts TCT outcomes after a 30 h course of treatment. We have previously reported a favorable TCT response in this cohort [15], with significant improvements in MCCB verbal learning t-scores (d = 0.65-082), and reductions in auditory hallucinations (d = −0.58), consistent with existing literature [6]. Based on our previous report [37], we hypothesized that there would be significant changes in MMN and P3a in recordings completed immediately before and after the 1st hour of TCT, and that the degree of this initial change would predict post-treatment improvements in verbal learning and positive symptom severity.…”

“…The "bottom up" approach of TCT is congruent with mounting evidence that abnormalities in early auditory information processing (EAIP) substantially contribute to impairments in higher-order cognitive and psychosocial functioning [10][11][12][13][14][15][16]. Efficacy trials in schizophrenia patients have shown that TCT improves higher-order cognitive functioning [6,9,15,[17][18][19][20], particularly in the domain of verbal learning. However, individual responses to TCT vary, with up to 45% of patients exhibiting minimal or no benefit even after extended therapeutic "doses" [21].…”

“…The MCCB is a reliable and comprehensive neurocognitive battery designed for treatment studies involving schizophrenia populations. Since previous studies [6][7][8][9], including Thomas et al [15], have demonstrated that TCT produces significant improvements in verbal learning, the MCCB verbal learning t-scores (corrected for age and sex) were the primary outcome measures of interest.…”

“…These cognitive impairments are targeted by only a limited number of interventions, and persist following medication stabilization [4,5]. One promising intervention, auditory-based targeted cognitive training (TCT), aims to drive improvements in higher-order cognitive function (i.e., verbal learning) via enhancement of basic auditory information processing [6][7][8][9]. The "bottom up" approach of TCT is congruent with mounting evidence that abnormalities in early auditory information processing (EAIP) substantially contribute to impairments in higher-order cognitive and psychosocial functioning [10][11][12][13][14][15][16].…”

Selective Loss of Smaller Spines in Schizophrenia

“…The predicted cognitive consequences of new/transient spine reductions, in a general sense, would be impairments known to affect individuals with schizophrenia: deficits in new learning 41 . Recently, auditory training exercises have shown promise for remediating auditory processing deficits in schizophrenia patients 42 . Impairments in the generation or stabilization of new/transient spines in some subjects with schizophrenia may limit the available gains through such an approach.…”