Computerized cognitive training restores neural activity within the reality monitoring network in schizophrenia

Abstract

Schizophrenia patients suffer from severe cognitive deficits, such as impaired reality monitoring. Reality monitoring is the ability to distinguish the source of internal experiences from outside reality. During reality monitoring tasks, schizophrenia patients make errors identifying "I made it up" items, and even during accurate performance, they show abnormally low activation of the medial prefrontal cortex (mPFC), a region that supports self-referential cognition. We administered 80 hr of computerized training of cognitive processes to schizophrenia patients and found improvement in reality monitoring that correlated with increased mPFC activity. In contrast, patients in a computer games control condition did not show any behavioral or neural improvements. Notably, recovery in mPFC activity after training was associated with improved social functioning 6 months later. These findings demonstrate that a serious behavioral deficit in schizophrenia, and its underlying neural dysfunction, can be improved by well-designed computerized cognitive training, resulting in better quality of life.

Figure 1. Pre-Training (Baseline) Performance and Brain Activation Differences between Healthy Comparison (HC) and Schizophrenia Subjects (SZ) during a Reality Monitoring Task

(A) Task Design: example of events within one trial. (B) Behavior: Mean accuracy averaged across 3 runs for self-generated and externally-presented item-identification is illustrated. One-way ANOVA, comparing mean raw scores for self-generated and externally-presented item identification, reveals significant impairment in SZ subjects during accurate identification of self-generated items, but not for identification of externally-presented items. One-way ANOVA, comparing mean d-prime statistical scores for overall source memory identification of word items between HC and SZ subjects, reveals significant impairment in SZ subjects during overall source-memory accuracy. (C) Signal increase in mPFC for the self-generated condition vs. the externally-presented condition across 15 HC subjects within the a priori mPFC ROI centered at co-ordinates (−4, 52, 8). (See also Figure S1 and Table S1 for whole brain analyses at baseline in each group, across (A) 15 HC and (B) 31 SZ subjects). (D–E) Mean mPFC signal is illustrated in beta weights averaged across all voxels within the a priori spherical mPFC ROI. All error bars represent s.e.m.

Figure 2. Cognitive Training Effects: Performance and Brain Activation Differences (at 16 Weeks) between Active Training Schizophrenia Subjects (SZ-AT), Control Condition Computer Games Schizophrenia Subjects (SZ-CG), and Healthy Comparison Subjects (HC)

(A–B) Mean accuracy averaged across 3 runs for self-generated and externally-presented item-identification, d-prime scores and mean mPFC signal are illustrated. Repeated measures ANOVAs reveal group differences at 16 weeks compared to baseline in: (A) Self-generated item accuracy, but not externally-presented item accuracy, and (B) D-prime scores for overall source memory identification of word items, as well as in mPFC reality monitoring signal averaged across all voxels within the a priori spherical ROI. (C) Reality monitoring activity in mPFC across 15 SZ-AT subjects after cognitive training compared to baseline within the a priori mPFC ROI (See also Figure S2 and Table S2 for the whole brain analyses of reality monitoring mPFC activity at 16 weeks versus baseline in each group, across (A) 15 SZ-AT, (B) 14 SZ-CG, and (C) 12 HC subjects). (D–E) Mean mPFC signal is illustrated in beta weights averaged across all voxels within the a priori spherical ROI in the SZ-AT group after training. All error bars represent s.e.m.

Figure 3. Association of Reality Monitoring Performance and Medial Prefrontal Activation Levels with Verbal Memory in Active Training Schizophrenia Subjects (SZ-AT) after 16 Weeks of Intervention

(A) Partial two-tailed correlations, controlling for age, education and IQ, show a significant association in SZ-AT subjects after 16 weeks of cognitive training (n=16) between overall source memory accuracy on the reality monitoring task and delayed verbal memory recall, (B) Two-tailed correlations show a significant association in SZ-AT subjects after 16 weeks of cognitive training (n=15) between mPFC signal within the a priori ROI after 16 weeks with delayed verbal memory recall.

Figure 4. Social Functioning Six Months after Cognitive Training

Two-tailed correlations show a significant association in SZ-AT subjects (n=13) between reality monitoring mPFC signal within the a priori ROI at 16 weeks, and social functioning ratings assessed 6 months after cognitive training was completed.