Neural Mechanisms of Psychomotor Slowing in Individuals at Clinical High-risk for Developing Psychosis

Osborne, Kenneth Juston

doi:https://doi.org/10.21985/n2-hacn-nb67

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Neural Mechanisms of Psychomotor Slowing in Individuals at Clinical High-risk for Developing Psychosis

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Motor abnormalities (e.g., dyskinesia, psychomotor slowing, neurological soft signs) are core features of schizophrenia observed from the premorbid period through chronic illness, suggesting motor dysfunction may reflect the pathophysiology of psychosis. Among this list of motor abnormalities, psychomotor slowing in particular is one of the most consistently observed and robust findings in the field. For example, psychomotor slowing has been shown to predict transition in those at high-risk for psychosis and is associated with symptom progression and recovery in patients with psychotic disorders. Notably, the vast majority of psychomotor research in psychosis has collapsed across the various cognitive (prefix “psycho”) and motor execution (root word “motor”) sub-processes that may contribute to slowing in psychosis. Electrophysiology research in schizophrenia suggests impaired motor activation and preparation may underlie psychomotor slowing. However, research in patients with psychosis is limited by effects of 3rd variable confounds such as medication side effects and illness duration. To address these limitations, much research has used individuals at clinical high-risk (CHR) for psychotic disorder. Despite behavioral studies suggesting similar motor dysfunction in those at CHR for psychosis, there have been no studies examining neural mechanisms of psychomotor slowing in the CHR period, where research can inform pathophysiological and risk models.This dissertation sought to examine the potential neural mechanisms of psychomotor slowing in those at CHR for psychosis and their potential relationships with clinical symptoms and illness progression through two complementary electrophysiological experiments. The primary goal of Experiment 1 was to determine if behavioral psychomotor slowing (i.e., reaction time slowing) is present in those at CHR for psychosis compared to healthy controls, and then determine if motor activation and preparation (indexed by lateralized readiness potential [LRP] amplitude) is a potential neural mechanism underlying reaction time slowing in those that meet CHR criteria for psychosis. In addition, I examined potential associations between psychomotor slowing and neural measures (i.e., LRP amplitude) of motor activation and symptoms. Results suggest individuals at CHR for psychosis exhibit behavioral slowing and primary motor deficits in activating and preparing behavioral responses. Further, blunted LRP amplitude was associated with worsening of negative symptoms at 12-month follow-up. The primary goal of Experiment 2 was to determine if slowing deficits detected in the those at CHR for psychosis are linked to either response selection and/or response execution processes, and to determine if this dysfunction is associated with symptom severity. Contrary to hypotheses and findings from Experiment 1, those at CHR for psychosis did not exhibit deficits in either response selection or response execution processes. This may suggest that the presence of response competition (as in Experiment 1) may be an important factor for understanding psychomotor slowing in the high-risk period. Together, these findings are broadly consistent with LRP studies in psychosis and implicate motor activation deficits as potential mechanisms of motor dysfunction in the high-risk period.

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