Date of Award

Spring 2023

Project Type

Dissertation

Program or Major

Psychology

Degree Name

Doctor of Philosophy

First Advisor

Jill A McGaughy

Second Advisor

Brett Gibson

Third Advisor

Amy Ramage

Abstract

Converging evidence supports the need to understand the unique contributions of the anterior cingulate cortex (ACC) in attention. The ACC has been implicated in filtering distractors, determining the relevance of stimuli, generating prediction errors, conflict monitoring, and goal-oriented behavioral changes. Unfortunately, much of this work has used broad definitions of ACC, which have often captured activity or deficits in regions outside of the ACC. Specific attention to the ACC, without concomitant damage to other regions of the prefrontal cortex is necessary to illuminate the specific role of the ACC in attention. Dysfunction of the ACC in humans is implicated in many neuropsychiatric disorders, such as depression, ADHD, and schizophrenia. All of these disorders predominantly begin in adolescence and are thought to be worsened by stress during this period. Longitudinal studies have shown that impairments in filtering salient distractors, sustained attention, cognitive flexibility, and stress in adolescence predict poorer disorder prognosis. What makes this critically concerning is that current pharmacological interventions are unable to lift attentional symptoms across the lifespan and are ineffective at addressing all symptoms in adolescents. To address this gap, preclinical models have been used to separate the functional and neurochemical specificity of the subregions of the prefrontal cortex. This allows for a better understanding of the specific neurochemical underpinning of select attentional impairments/symptoms. The present series of work focuses not only on the selective contributions of ACC to attention, using a cross-species translational attentional set shifting task, but also the neurochemical specificity for these impairments. In addition, this work assesses ACC when it is immature; exploring the combined effects of acute stress and cognitive load which is known to tax ACC. Together the data support a specific role for the ACC in filtering distractors when they have a prior reinforcement history, which is impaired following cholinergic, but not noradrenergic lesions to ACC. The combination of acute stress and cognitive load produces impairment in subjects with in-tact ACC and exacerbated this even more in adolescent subjects. Together, suggesting that the immaturities in the ACC promote a vulnerability to stress and ACC-taxing attentional demands due to overlapping recruitment. The data also serve to further separate the ACC from the prelimbic cortex (PL). In the PL, cognitive rigidity is not seen in adults following acute stress. Adolescent subjects, however, are more cognitively rigid under conditions of combined stress and increased cognitive load. This was linked to increased rates of Fos-activated cells colocalized with noradrenergic axons in the PL, suggesting a double recruitment of the corticopetal noradrenergic system by stress and attentional set shifting demands, which the immature PL was unable to cope with. These results are in alinement with the ACC having a specific function, separate from other regions of the prefrontal cortex, and that stress in conjunction with an increased attentional load while the prefrontal cortex is immature results in exacerbated deficits, like those seen in neuropsychiatric disorders.

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