Institution: University of Michigan, Ann Arbor, Michigan 48109
Abstract: Cue-directed shifts from ongoing behavior to initiating new (cue-directed) behavior are critical for many tasks, including changing direction and avoiding falls. Rodent studies have shown that transient activations of the cholinergic system are necessary and sufficient for producing cue- directed shifts of attention and response in the Sustained Attention Task (SAT). Other rodent studies suggest that cue-triggered shifts from an ongoing motor task (e.g. walking) to a new motor task (e.g. turning) are also cholinergically mediated. These findings have potential implications for patients with Parkinson’s disease: falls in such patients often occur in turning situations and are more related to cholinergic declines than to the dopaminergic declines that are the hallmark of the disease. We first re-analyzed a human fMRI SAT dataset using psychophysiological interaction (PPI) and found increased interactions between specific cortical and striatal regions during shifts from ongoing to cue-directed behavior. To test the hypothesis that these would generalize to a shift in motor behavior, we next reanalyzed Stop Signal Task (SST) fMRI data from a public dataset, asking whether the functional co-activation correlations showed similar patterns as the PPI- identified striatal and cortical connections in the SAT. Linear regression analysis of the SST fMRI data found that the striatal ‘seed’ region’s activation for the Correct Stop vs Correct Go contrast predicts a significant amount of the variance in the a priori target regions identified from the SAT dataset for the same contrast. This indicates that there is correlation in the activity between the two regions during the trials where a cue-triggered change in movement occurs. This finding provides converging evidence that interactions between these striatal regions and higher processing cortical regions are important for cue-guided shifts in task sets, including motor-based task sets.
Keywords: Parkinson’s Disease; fMRI; cholinergic system; cue-guided shifts