A randomized clinical trial of plasticity-based cognitive training in mild traumatic brain injury.

Clinical practice guidelines support cognitive rehabilitation for people with a history of mild traumatic brain injury (mTBI) and cognitive impairment, but no class I randomized clinical trials have evaluated the efficacy of self-administered computerized cognitive training. The goal of this study was to evaluate the efficacy of a self-administered computerized plasticity-based cognitive training programmes in primarily military/veteran participants with a history of mTBI and cognitive impairment. A multisite randomized double-blind clinical trial of a behavioural intervention with an active control was conducted from September 2013 to February 2017 including assessments at baseline, post-training, and after a 3-month follow-up period. Participants self-administered cognitive training (experimental and active control) programmes at home, remotely supervised by a healthcare coach, with an intended training schedule of 5 days per week, 1 h per day, for 13 weeks. Participants (149 contacted, 83 intent-to-treat) were confirmed to have a history of mTBI (mean of 7.2 years post-injury) through medical history/clinician interview and persistent cognitive impairment through neuropsychological testing and/or quantitative participant reported measure. The experimental intervention was a brain plasticity-based computerized cognitive training programme targeting speed/accuracy of information processing, and the active control was composed of computer games. The primary cognitive function measure was a composite of nine standardized neuropsychological assessments, and the primary directly observed functional measure a timed instrumental activities of daily living assessment. Secondary outcome measures included participant-reported assessments of cognitive and mental health. The treatment group showed an improvement in the composite cognitive measure significantly larger than that of the active control group at both the post-training [+6.9 points, confidence interval (CI) +1.0 to +12.7, P = 0.025, d = 0.555] and the follow-up visit (+7.4 points, CI +0.6 to +14.3, P = 0.039, d = 0.591). Both large and small cognitive function improvements were seen twice as frequently in the treatment group than in the active control group. No significant between-group effects were seen on other measures, including the directly-observed functional and symptom measures. Statistically equivalent improvements in both groups were seen in depressive and cognitive symptoms.

Online Social Cognition Training in Schizophrenia: A Double-Blind, Randomized, Controlled Multi-Site Clinical Trial.

Social cognition (SC), the mental operations underlying social functioning, are impaired in schizophrenia. Their direct link to functional outcome and illness status have made them an important therapeutic target. However, no effective treatment for these deficits is currently applied as a standard of care. To address this need, we have developed SocialVille-an online, plasticity-based training program that targets SC deficits in schizophrenia. Here we report the outcomes of a double-blind, controlled, randomized, multi-site clinical trial of SocialVille. Outpatients with schizophrenia were randomized to complete 40 sessions of either SocialVille (N = 55 completers) or active control (computer games; N = 53 completers) from home. The a priori co-primary outcome measures were a social cognitive composite and a functional capacity outcome (UCSD Performance-based Skills Assessment [UPSA-2]). Secondary outcomes included a virtual functional capacity measure (VRFCAT), social functioning, quality of life, and motivation. Linear mixed models revealed a group × time interaction favoring the treatment group for the social cognitive composite (b = 2.81; P < .001) but not for the UPSA-2 measure. Analysis of secondary outcome measures showed significant group × time effects favoring the treatment group on SC and social functioning, on the virtual functional capacity measure and a motivation subscale, although these latter findings were nonsignificant with FDR correction. These results provide support for the efficacy of a remote, plasticity-based social cognitive training program in improving SC and social functioning in schizophrenia. Such treatments may serve as a cost-effective adjunct to existing psychosocial treatments. Trial Registration: NCT02246426.

Alertness Training Improves Spatial Bias and Functional Ability in Spatial Neglect.

OBJECTIVE: We conducted a multisite, randomized, double-blinded, controlled trial to examine the effectiveness of a digital health intervention targeting the intrinsic regulation of goal-directed alertness in patients with chronic hemispatial neglect. METHODS: Forty-nine participants with hemispatial neglect, who demonstrated significant spatially biased attention after acquired brain injury, were randomly assigned to the experimental attention remediation treatment or the active control group. The participants engaged with the remotely administered interventions for 12 weeks. The primary outcome was spatial bias on the Posner cueing task (response time difference: left minus right target trials). Secondary outcomes included functional abilities (measured via the Catherine Bergego scale and Barthel index), spatial cognition, executive function, quality of life, and sleep. Assessments were conducted before and immediately after participation in the experimental intervention or control condition, and again after a 3-month no-contact period. RESULTS: Compared with the active control group, the intervention group exhibited a significant improvement in the primary outcome, a reduction in spatially biased attention on the Posner cueing task (p = 0.010, Cohen's d = 0.96), in addition to significant improvements in functional abilities as measured on the Catherine Bergego and Barthel indices (p = 0.027, Cohen's d = 0.24). INTERPRETATION: Our results demonstrate that our attention training program was effective in improving the debilitating attention deficits common to hemispatial neglect. This benefit generalized to improvements in real-world functional abilities. This safe, highly scalable, and self-administered treatment for hemispatial neglect might serve as a useful addition to the existing standard of care. ANN NEUROL 2020;88:747-758.

Evaluation of a plasticity-based cognitive training program in schizophrenia: Results from the eCaesar trial.

OBJECTIVE: Cognitive impairment in schizophrenia is a core feature of the disorder. Computerized cognitive training has shown promise in pilot studies. A 26-week randomized blinded placebo-controlled trial was conducted to investigate the effect of a novel computerized cognitive training program on cognitive and functional capacity outcomes. METHOD: The study followed MATRICS guidelines for the evaluation of interventions designed to improve cognitive function in schizophrenia. Participants (N = 150) were randomized to experimental (computerized cognitive training in a game-like format) or active control (computer games) groups. Training was conducted in-clinic, with an intended training schedule of 5 days per week, 1 h per day, for 26 weeks. Co-primary outcome measures were the MATRICS Consensus Cognitive Battery (MCCB) composite score and the UCSD Performance-Based Skills Assessment (UPSA-2) total score, secondary outcome measures included the Cognitive Assessment Interview (CAI) and the Short-Form-12 Mental Composite Score (SF-12 MCS). Target engagement was assessed with task-learning based assessment. RESULTS: At baseline, the groups were well matched. No significant effect of the experimental treatment was seen on the primary or secondary outcome measures compared to the active control. Review of the task learning/target engagement data suggested inadequate target engagement. CONCLUSIONS: Results do not support a cognitive or functional capacity benefit from this implementation of a computerized cognitive training program in people with schizophrenia. In future trials, careful consideration is merited of the assessment of task learning/target engagement, the effects of making the cognitive training game-like on motivation, and the implicit effects of trial requirements on participant selection.