Arousal-Dependent Brain Markers in fMRI Linked to Psychopathology and Cognition

Abstract

Arousal states range from high levels of alertness to low levels of drowsiness and sleep. Strong behavioral evidence suggests that arousal relates to psychopathology and cognition; however, the brain markers underlying these relationships remain poorly understood. The premise of my dissertation is to determine whether arousal-dependent fMRI markers relate to psychopathology, including anxiety levels, cognitive task performance, and cognitive impairment in schizophrenia spectrum disorder. In Aim 1, I tested whether three fMRI global measures of arousal (fMRI arousal index, global mean signal, and percent heart rate variation explained) were associated with anxiety. I found that an fMRI arousal index marker and global mean signal were spatially and temporally associated with anxiety. In Aim 2, I examined whether the switching rate of salience network, default mode network, and central executive network were arousal dependent, and used advanced statistical modeling to identify which characteristics of the fMRI signal contributed to its arousal dependencies. Finally, within Aim 2, I tested whether arousal state moderated the relationship between average (global) switching rate and cognitive task performance. I found that the switching rates of anterior salience network and default mode network were arousal-dependent, and that these dependencies were driven by static correlation, and that arousal moderated the relationship between global switching and cognitive task performance. In Aim 3, I tested whether autonomic arousal explained switching rate abnormalities found in schizophrenia spectrum disorder and whether arousal’s modulatory role in global switching rate was intact. I found that autonomic arousal did not explain switching rate abnormalities in schizophrenia spectrum disorder and that arousal’s modulatory effect on global switching was disrupted in schizophrenia. In summary, the findings of my dissertation suggest that arousal-dependent fMRI markers may provide valuable insight into the mechanisms linking arousal to psychopathology and cognition, and how these relationships may be disrupted in clinical populations.