Ian S. Ramsay

Affective and executive network processing associated with persuasive antidrug messages

Previous research has highlighted brain regions associated with socioemotional processes in persuasive message encoding, whereas cognitive models of persuasion suggest that executive brain areas may also be important. The current study aimed to identify lateral prefrontal brain areas associated with persuasive message viewing and understand how activity in these executive regions might interact with activity in the amygdala and medial pFC. Seventy adolescents were scanned using fMRI while they watched 10 strongly convincing antidrug public service announcements (PSAs), 10 weakly convincing antidrug PSAs, and 10 advertisements (ads) unrelated to drugs. Antidrug PSAs compared with nondrug ads more strongly elicited arousal-related activity in the amygdala and medial pFC. Within antidrug PSAs, those that were prerated as strongly persuasive versus weakly persuasive showed significant differences in arousal-related activity in executive processing areas of the lateral pFC. In support of the notion that persuasiveness involves both affective and executive processes, functional connectivity analyses showed greater coactivation between the lateral pFC and amygdala during PSAs known to be strongly (vs. weakly) convincing. These findings demonstrate that persuasive messages elicit activation in brain regions responsible for both emotional arousal and executive control and represent a crucial step toward a better understanding of the neural processes responsible for persuasion and subsequent behavior change.

Increases in Intrinsic Thalamocortical Connectivity and Overall Cognition Following Cognitive Remediation in Chronic Schizophrenia

BACKGROUND Thalamic projections to the prefrontal cortex (PFC) are critical for cognition, and disruptions in these circuits are thought to underlie the pathophysiology of schizophrenia. Cognitive remediation (REM) is a behavioral intervention that holds promise for improving cognition and functioning in schizophrenia, however the extent to which it affects thalamo-prefrontal connections has not been researched. This study sought to determine whether patients with schizophrenia who undergo a placebo-controlled trial of REM show increased functional connectivity between the thalamus and PFC, and whether these changes correspond to improvements in cognition. METHODS Twenty-six patients with chronic schizophrenia were randomized to either 48 hours (over 16 weeks) of a drill-and-practice working memory-focused REM or an active placebo condition. All participants underwent cognitive assessment (MATRICS Consensus Cognitive Battery), as well as both resting and task-based fMRI before and after their respective intervention. All clinicians, technicians, and raters were blind to participant condition. RESULTS We observed changes in resting-state connectivity in the PFC for the REM group but not the placebo group. Increased intrinsic connectivity between the thalamus and right middle frontal gyrus correlated with improvements in overall cognition. Additionally, lower baseline cognition correlated with greater increases in connectivity between the thalamus and PFC. Similar findings were observed when patients were scanned during a working memory task. CONCLUSIONS These results suggest that increases in thalamo-prefrontal circuitry correspond with training-related improvements of the cognitive deficits associated with schizophrenia.

Response to Targeted Cognitive Training Correlates with Change in Thalamic Volume in a Randomized Trial for Early Schizophrenia

Reduced thalamic volume is consistently observed in schizophrenia, and correlates with cognitive impairment. Targeted cognitive training (TCT) of auditory processing in schizophrenia drives improvements in cognition that are believed to result from functional neuroplasticity in prefrontal and auditory cortices. In this study, we sought to determine whether response to TCT is also associated with structural neuroplastic changes in thalamic volume in patients with early schizophrenia (ESZ). Additionally, we examined baseline clinical, cognitive, and neural characteristics predictive of a positive response to TCT. ESZ patients were randomly assigned to undergo either 40 h of TCT (N=22) or a computer games control condition (CG; N=22 s). Participants underwent MRI, clinical, and neurocognitive assessments before and after training (4-month interval). Freesurfer automated segmentation of the subcortical surface was carried out to measure thalamic volume at both time points. Left thalamic volume at baseline correlated with baseline global cognition, while a similar trend was observed in the right thalamus. The relationship between change in cognition and change in left thalamus volume differed between groups, with a significant positive correlation in the TCT group and a negative trend in the CG group. Lower baseline symptoms were related to improvements in cognition and left thalamic volume preservation following TCT. These findings suggest that the cognitive gains induced by TCT in ESZ are associated with structural neuroplasticity in the thalamus. Greater symptom severity at baseline reduced the likelihood of response to TCT both with respect to improved cognition and change in thalamic volume.

Neuroplastic changes in patients with schizophrenia undergoing cognitive remediation: triple-blind trial

BackgroundPatients with schizophrenia have shown cognitive improvements following cognitive remediation, but the neuroplastic changes that support these processes are not fully understood.AimsTo use a triple-blind, placebo-controlled trial to examine neural activation before and after cognitive remediation or a computer skills training (CST) placebo (trial registration: NCT00995553)).MethodTwenty-seven participants underwent functional magnetic resonance imaging before and after being randomised to either cognitive remediation intervention or CST. Participants completed two variants of the N-back task during scanning and were assessed on measures of cognition, functional capacity, community functioning and symptoms.ResultsWe observed a group × time interaction in the left prefrontal cortex, wherein the cognitive remediation group showed increased activation. These changes correlated with improved task accuracy within the cognitive remediation group, whereas there was no relationship between changes in activation in untrained cognitive measures. Significant changes were not observed in other hypothesised areas for the cognitive remediation group.ConclusionsWe replicated the finding that cognitive remediation increases left lateral prefrontal activation during a working memory task in patients with schizophrenia, suggesting this may be an important neural target for these types of interventions.

Model selection and prediction of outcomes in recent onset schizophrenia patients who undergo cognitive training

Predicting treatment outcomes in psychiatric populations remains a challenge, but is increasingly important in the pursuit of personalized medicine. Patients with schizophrenia have deficits in cognition, and targeted cognitive training (TCT) of auditory processing and working memory has been shown to improve some of these impairments; but little is known about the baseline patient characteristics predictive of cognitive improvement. Here we use a model selection and regression approach called least absolute shrinkage and selection operator (LASSO) to examine predictors of cognitive improvement in response to TCT for patients with recent onset schizophrenia. Forty-three individuals with recent onset schizophrenia randomized to undergo TCT were assessed at baseline on measures of cognition, symptoms, functioning, illness duration, and demographic variables. We carried out 10-fold cross-validation of LASSO for model selection and regression. We followed up on these results using linear models for statistical inference. No individual variable was found to correlate with improvement in global cognition using a Pearson correlation approach, and a linear model including all variables was also found not to be significant. However, the LASSO model identified baseline global cognition, education, and gender in a model predictive of improvement on global cognition following TCT. These findings offer guidelines for personalized approaches to cognitive training for patients with schizophrenia.