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.