Neural Correlates of Self-regulatory Fatigue and the Role of High Affinity Striatal Dopaminergic Receptors in Tourette Syndrome and Healthy Subjects
Year: 2020
Type: dissertation
Study design: Observational Study
Abstract: Tourette syndrome (TS) is a developmental neuropsychiatric condition characterized by motor and vocal tics. Tics are semi-voluntary movements or vocalizations that are stereotyped, repetitive and non-rhythmic. They usually occur in response to a premonitory urge, and can be suppressed temporarily. TS typically involves multiple comorbidities, in particular obsessive-compulsive disorder, attention deficit/hyperactivity disorder, and emotional dysregulation. Given the clinical phenomenology, TS has been conceptualized as a syndrome of inhibitory deficits involving motor, cognitive, emotional and behavioral domains. Neuroimaging studies have implicated the cortico-striato-thalamo-cortical circuitry, in particular the striatal dopamine system, and cortical control areas. However, despite numerous studies, findings have been mixed, and a definitive explanation of the neurobiology underlying TS has remained elusive. The objective of this body of work was to utilize novel neuroimaging approaches in an attempt to identify neural mechanisms that could contribute to the manifestation of TS. In a positron emission tomography (PET) imaging study of the striatum, I investigated striatal D2/3 dopamine receptors in TS using the radioligands [11C]raclopride and [11C]-(+)-PHNO, an agonist that binds preferentially to D3 receptors, thus allowing higher sensitivity and measurement of receptors in a high affinity state. Eleven adults with TS and 11 matched healthy control (HC) participants underwent [11C]raclopride and [11C]-(+)-PHNO PET scans. There were no significant group differences between TS and HC participant binding potentials (BPND) in ventral, motor and associative striatum. In a functional magnetic resonance imaging (fMRI) study of self-regulatory fatigability using an eye blink inhibition paradigm, high-performing HC participants had relatively higher activation in known prefrontal cortex (PFC) control areas – inferior frontal gyrus (IFG), dorsolateral prefrontal cortex (DLPFC), and supplemental motor area (SMA) – whereas self-regulatory fatigability was associated with relatively higher activation in ventromedial PFC, rostroventral anterior cingulate cortex (ACC), and orbitofrontal cortex (OFC). Based on these findings, I carried out a region of interest (ROI) analysis comparing 19 HC and 12 TS participants. There was substantially less percent signal change in the DLPFC/IFG and SMA ROIs in the TS group in comparison to the HC group. These findings suggests that self-regulatory deficits in TS arise from fatigability in cortical control.
Source: TSpace (University of Toronto)
Author: Elia Abi‐Jaoude
Language: English
Subfield: Clinical Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: green
OpenAlex ID: W3134202840