Task-independent effects are potential confounders in longitudinal imaging studies of learning in schizophrenia

• A robust method was used to identify task-independent fMRI BOLD changes in a multiday learning experiment in schizophrenia
• Task-independent effects were apparent in healthy control group and schizophrenia but differed in direction and magnitude
• In schizophrenia they were greater in magnitude and most prominent in areas of the salience and default mode networks
• Unless properly accounted for, these effects will compromise precise interpretation of fMRI learning data in schizophrenia.

Learning impairment is a core deficit in schizophrenia that impacts on real-world functioning and yet, elucidating its underlying neural basis remains a challenge. A key issue when interpreting learning-task experiments is that task-independent changes may confound interpretation of task-related signal changes in neuroimaging studies. The nature of these task-independent changes in schizophrenia is unknown. Therefore, we examined task-independent “time effects” in a group of participants with schizophrenia contrasted with healthy participants in a longitudinal fMRI learning-experiment designed to allow for examination of non-specific effects of time. Flanking the learning portions of the experiment with a task-of-no-interest allowed us to extract task-independent BOLD changes. Task-independent effects occurred in both groups, but were more robust in the schizophrenia group. There was a significant interaction effect between group and time in a distributed activity pattern that included inferior and superior temporal regions, frontal areas (left anterior insula and superior medial gyri), and parietal areas (posterior cingulate cortices and precuneus). This pattern showed task-independent linear decrease in BOLD amplitude over the two scanning sessions for the schizophrenia group, but showed either opposite effect or no activity changes for the control group. There was a trend towards a correlation between task-independent effects and the presence of more negative symptoms in the schizophrenia group.The strong interaction between group and time suggests that both the scanning experience as a whole and the transition between task-types evokes a different response in persons with schizophrenia and may confound interpretation of learning-related longitudinal imaging experiments if not explicitly considered.