Neural and behavioral correlates of proactive and reactive control in major depression: A study with functional magnetic resonance imaging and eye-tracking.

Proactive control describes preparatory, anticipatory processes prior to upcoming demands, whereas reactive control is recruited as a late, corrective response to goal interferences. Here, we used fMRI to investigate behavioral and neuronal correlates of proactive and reactive control in major depressive disorder (MDD). Fifty patients and 50 healthy controls performed an antisaccade task with trial-specific central cues informing about the probability of upcoming task demands (antisaccade or prosaccade), thereby manipulating proactive control levels in the cue period. The trial-specific task instruction was contained in the peripheral stimulus, resulting in either congruent or incongruent trials in the saccadic response period to tax reactive control. Saccade stimuli were faces, with differently valenced expressions (negative, positive, neutral) allowing block-wise affective manipulation. Results indicated comparable effects of cue period proactive control in both groups in fronto-parieto-occipital cortex and striatum, including medial frontal and supplementary eye fields. In the response period, incongruent trials evoked enhanced activations in fronto-cingular, parietal and temporal cortex, thalamus and striatum, again without group differences. However, patients with MDD had larger antisaccade amplitudes and lower saccadic peak velocities. Exploratory analysis of a posterior parietal region-of-interest known to be related to non-standard sensorimotor transformations in antisaccades indicated reduced BOLD in patients during the response phase. There were no effects of stimulus valence on any measure. Together, these findings support the role of overlapping fronto-parieto-striatal networks in proactive and reactive control and suggest that in this particular task, such activations may be unaffected by stimulus-induced affective states as well as clinically relevant affective disorder.