Attention impairment in depression and anxiety

Our experience of the world is defined not only by what surrounds us, but also by what we pay attention to. Because goal-directed attention is essential for so many aspects of cognition, from perception to learning to decision-making, impairments of attention in the context of mental illness can be severely debilitating. Despite this impact, we know relatively little from human neuroscience about the specific attention impairments that comprise "concentration difficulties, " a symptom and diagnostic criterion of mood and anxiety disorders that is often not alleviated with current first-line treatments. In this dissertation, I aim to better understand mechanisms of goal-directed attention in healthy adults and characterize various forms of attention impairment in individuals with depression and anxiety using multimodal human neuroscience methods. First, I review the state of the field regarding attention impairments in depression and anxiety (Chapter 1). I highlight both the key advances in cognitive neuroscience regard-ing the neural correlates of subtypes of attention and the ways in which these findings might inform precision psychiatry. Next, I investigate a potential neural correlate of selective attention in a sample of healthy adults using functional magnetic resonance imaging (fMRI) (Chapter 2). Using statistical analysis tools to disentangle ongoing neural activity from stimulus-driven activity, I demonstrate that stimulus-independent neural signals are associated with the sharing of attended visual information across the cortex. Leveraging these findings, I then characterize selective attention impairments in adults with Major Depressive Disorder using fMRI and electro-encephalography (EEG) (Chapter 3). I find that feature-based selective attention impairments are severe in a subset of depressed individuals and are specifically associated with fronto-parietal hypo-connectivity and de-creased posterior alpha oscillations, consistent with my prior observations of selective attention correlates in healthy adults. I then develop a machine-learning algorithm that can successfully predict changes in selective attention with antidepressant pharmacotherapy and show that stressors occurring in childhood are associated with poorer selective attention in depressed adults (Chapter 4). In a study of individuals with a range of mood and anxiety symptoms, I develop nov-el behavioral paradigms to assess transdiagnostic sub-domains of attention impairment (Chapter 5). These data reveal that spatial attention impairments partially mediate the association between early life stress and anxiety and are associated with increased anxiety and concentration problems during the COVID-19 pandemic. Finally, I put forward a theoretical model for how attention may become impaired in depression and anxiety and detail important directions for future research (Chapter 6). Together, these findings provide insight into the neural mechanisms underlying different subdomains of attention, clarify our understanding of attention impairments as a transdiagnostic symptom dimension, and identify neural targets for the development of more personalized treatment, setting the stage for future studies in both basic and clinical neuroscience

Advisor: Williams Leanne M.
Gardner Justin
Gotlib Ian H.
Greicius Michael D.
Grill-Spector Kalanit