AbstractsPsychology

Rodent studies indicate that cholinergic inputs to frontoparietal cortex play an important role in signal detection, especially in challenging conditions. fMRI studies have likewise shown frontoparietal activity in humans under task conditions parallel to those used in the rodent studies. While these parallels are suggestive, the degree to which the fMRI activation patterns seen in humans reflect cholinergic activity remains unknown. The studies in this dissertation provide stronger evidence for cholinergic influences on the brain systems supporting attention in humans, and begin to delineate how those influences may differ by brain region and interact with other (e.g. dopaminergic) influences to shape cognition and behavior. First, an electroencephalography study showed that gamma synchronization, which previous studies have linked to cholinergic activity and attentional control, increases in response to a distractor challenge. Furthermore, across participants, greater increases in gamma synchronization in parietal cortex were associated with better distractor resistance, whereas greater increases in gamma dispersion in right prefrontal cortex were associated with greater response time variations thought to reflect difficulty in maintaining consistent control. Another series of experiments leveraged variability in cholinergic integrity (measured using PET) in Parkinson???s patients as a natural experiment to determine cholinergic contributions to different aspects of attention and cognitive control. Thalamic cholinergic integrity made the strongest independent contribution to variation in the ability to detect signals under perceptual challenge, whereas cortical cholinergic integrity was the best independent predictor of the ability to resist content-rich distractors likely to draw attention away from the target signal. Exploratory analyses suggested that parietal cholinergic integrity might play an especially important role in resisting these distractors, consistent with the electroencephalography study results. Finally, a secondary data analysis of a larger sample suggested that in conditions making strong demands on executive control, there may be mutual compensation between cholinergic and dopaminergic systems. To summarize, the present findings provide further evidence for cholinergic contributions to frontoparietal brain systems supporting signal detection, attention, and cognitive control, more precisely define the contributions of thalamic, prefrontal, and parietal inputs, and suggest the possibility of mutual compensation with the dopaminergic system in situations of high executive demand.