Date of Award
Doctor of Philosophy (PhD)
A recent study has shown that the locus of the largest known dopamine abnormality between patients with schizophrenia and healthy controls is in the associative striatum (Kegeles et al., 2010). This dopamine abnormality in the associative striatum is thought to bring about aberrant salience assignment for patients, which may underlie symptoms of psychosis like delusions and hallucinations (Howes & Kapur, 2009). Interestingly, the associative striatum has segregated, looped, connectivity with cortical regions including the prefrontal and parietal cortices (Draganski et al., 2008; Redgrave, Vautrelle, & Reynolds, 2011) and computational models have suggested that it may function as an information gate during cognitive control (Frank, Loughry, & O'Reilly, 2001; Gruber, Dayan, Gutkin, & Solla, 2006), much the way that posterior portions of the striatum gate motor control (Chevalier & Deniau, 1990). The current study sought to explore the relationship between striatal involvement in cognition and aberrant salience symptom expression using a novel task of cognitive control. We examined aberrant salience using a self-report measure (Cicero et al., 2010) and core components of cognitive control (updating, interference control, and simple maintenance), that are critically reliant on intact information gating, in a sample of 22 patients with schizophrenia and 20 healthy controls using a slow event-related fMRI design. We predicted that 1) aberrant salience symptoms would be greater for patients than controls, 2) that patients would demonstrate increased errors during interference controls trials, given that patients may be inappropriately assigning salience to distracters, and 3) that striatal activity during those errors could be positively correlated with aberrant salience symptoms. We found a trend toward significant differences between patients and controls on aberrant salience symptom presence, and a significant difference between groups during updating performance. During interference control trials, although we found no difference between groups when participants were tasked with maintaining targets during distracter presentation, patients were more likely to make errors when probed with those distracters, suggesting inappropriate distracter updating. When examining the brain activity during correct and incorrect updating and interference control trials, for patients update trial activity in the prefrontal cortex and striatum was significantly lower for incorrect updating trials when compared to correct updating trials, and significantly greater when patients inappropriately identified the distracter as correct compared with trials when they correctly rejected the distracter. Activity did not differ between correct and incorrect updating or interference control trials for controls. Further, we found that for patients, as predicted, the increase of activity during incorrect distracter trials was positively correlated with aberrant salience symptoms, but only for the associative striatal region and not the prefrontal region. We found no relationship between aberrant salience and patient brain activity during correct distracter trials, nor did we find significant relationships between aberrant salience and brain activity during either updating or interference control trials for controls. These results demonstrate that cognitive control deficits of patients demonstrate some domain selectivity, given that we found some evidence for preserved simple maintenance and maintenance in the face of task relevant distracter performance, but impaired performance at updating and ignoring distracters. Finally, we found evidence demonstrating a relationship between aberrant salience symptom expression for patients, cognitive deficits, and associative striatal activity. This relationship may have implications for treatments that improve cognitive function and reduce symptom expression.
Chair and Committee
Todd Braver, Tamara Hershey, Thomas Oltmanns, Steven Petersen,
Ceaser, Alan E., "Striatal Activity is Associated with Deficits of Cognitive Control and Aberrant Salience for Patients with Schizophrenia" (2015). Arts & Sciences Electronic Theses and Dissertations. 560.