Improving prefrontal cortex function in schizophrenia through focused training of cognitive control

Abstract

Previous research has shown that individuals with schizophrenia show deficits in cognitive control functions thought to depend on the lateral prefrontal cortex (PFC), and its interactions with related regions. The current study explored the effects of instructed strategy training on improving cognitive control functioning in patients with schizophrenia. Event-related fMRI was used to test whether effects of such training were associated with changes in brain activity dynamics during task performance. Patients with schizophrenia (N = 22) performed the AX-CPT cognitive control task in two-sessions, with the first occurring pre-training and second following strategy training. The training protocol emphasized direct encoding of contextual cues and updating response selection goals in accordance with cue information. A matched group of healthy controls (N = 14) underwent the same protocol but were only scanned in the pre-training session. In the pre-training session, patients exhibited behavioral evidence of impaired utilization of contextual cue information, along with reduced cue-related activity - but increased activation during probe and response periods - in a network of regions associated with cognitive control, centered on the lateral PFC. Following training, this pattern of activation dynamics significantly shifted, normalizing towards the pattern observed in controls. These activation effects were associated with both clinical symptoms and behavioral performance improvements. The results suggest that focused strategy training may facilitate cognitive task performance in patients with schizophrenia by changing the dynamics of activity within critical control-related brain regions.

Keywords: cognitive control; cognitive training; functional imaging; prefrontal cortex; remediation; schizophrenia.

Figure 1

(A) Brain regions showing group × event type interactions in patients and healthy controls and session × event type interactions in patients. Regions in red reflect greater blood oxygen level-dependent (BOLD) response at cue in controls relative to patients prior to training, and regions in blue reflect both greater BOLD response at cue in controls relative to patients prior to training and greater patient BOLD response at cue post-training relative to pre-training. (B) The time course plot shows control and patient pre-training and patient post-training cue and probe activity averaged across the nine regions showing both a group × event type interaction and a session × event type interaction shown in the images of the brain.

Figure 2

(A) Right inferior frontal junction region (x = + 45, y = + 10, z = + 30) showing significantly greater B-cue relative to A-cue in healthy controls prior to training and significantly greater B-cue relative to A-cue in patients post-training. (B) Pre-training B-cue activity averaged across sixteen regions showing significant group by event type interactions negatively correlated with disorganized symptoms global score (includes disorientation from attention, positive formal thought disorder, and bizarre behavior).

Figure 3

Training-related improvement in B-Cue activation in right inferior frontal junction (x = + 52, y = + 2, z = + 32) positively correlated with disorganized symptoms global score (includes disorientation from attention, positive formal thought disorder, and bizarre behavior).