What Can Different Motor Circuits Tell Us About Psychosis? 

An RDoC Perspective

Vijay A. Mittal; Jessica A. Bernard; Georg Northoff

Disclosures

Schizophr Bull. 2017;43(5):949-955. 

In This Article

Basal Ganglia Circuit and Motor Excitation/Inhibition Abnormalities

Particular motor behaviors, including spontaneous dyskinesias (hyper/hypokinetic movements that occur as a result of pathophysiology), or more basic motor behaviors, elicited by instrumental tasks designed to engage the same underlying circuit component dysfunction,[3] are closely tied to basal ganglia circuits, and as a result, can be powerful tools for understanding vulnerability, progression, and treatment response and further, for refining theories such as the dopamine (DA) hypothesis. By governing the selection or gating of a subset of representations that have been activated by the cortex, parallel basal ganglia circuits are responsible for modulating a range of higher order behaviors.[4,5] Basal ganglia circuits each share the same general organization, originating in specific cortical areas, passing though portions of the basal ganglia and thalamus, and then projecting back into the frontal cortical area of origin in a closed loop. Each circuit is also comprised of direct and indirect pathways that work in synchrony to balance inhibitory restraint on the thalamocortical output leading back to the cortex.[6] This intricate system is governed by a specific chemoarchitecture and multiple neurotransmitter interactions, with DA activity representing the primary modulatory chemical messenger.[6,7] As a result, the circuits are highly sensitive to DA abnormalities, and what is reflected by dysfunction in one BG circuit may speak to common factors that would impair functions of other BG circuits as well.[8] Thus, parameterizing motor behaviors or tracking changes in motor activity over time, or in response to treatment, may serve as sensitive outward marker of changes in an underlying system that modulates functions ranging from motor, cognitive, and emotional behavior to perception, affect, motivation and action.[4,5,9]

Within the context of the new RDoC domain, there are a number of promising constructs/subconstructs that hold significant relevance to mapping markers of basal ganglia circuit dysfunction. Constructs/subconstructs that tap into processes involved with initiation of a selected action plan or the inhibition of motor plans will provide a context for evaluating hypokinetic and hyperkinetic movements characteristic of basal ganglia circuit dysfunction in psychosis. For example, work from our research program has suggested that velocity scaling and force variability are highly sensitive to basal ganglia dysfunction in individuals with varying psychosis vulnerability.[10,11] There is additional evidence suggesting that these abnormalities are also present in schizophrenia patients.[12,13] Currently, we are working to evaluate how these experimental paradigms map on to other units of analysis across Motor Systems sub/constructs. This is an important line of inquiry as these motor behaviors clearly tie into underlying pathophysiology that drives clinically relevant outcomes. Indeed, recent work indicates that motor behaviors specific to the basal ganglia, as well as those that tap into basal ganglia function in addition to other networks (eg, gesture behavior), predict onset of psychosis in risk populations,[14–16] or functional outcome in individual with schizophrenia[17,18] (also see Commentary by Schiffman, this issue).

This system will also provide building blocks for examining circuit-motor behavior relationships in the context of investigating links with other existing RDoC domains. For example, basal ganglia circuits also contribute to functions included in the Cognitive Systems domain, allowing for flexible modulation of internally generated/externally evoked behavioral responses to environmental cues.[19,20] If related dysfunction prevents the execution of an initiated order, or does not effectively inhibit unintended orders, this can negatively impact cognitive function across domains.[8] In this framework, it is likely that movement abnormalities that are closely linked to underlying basal-ganglia circuit dysfunction may serve as useful components for integrated study; in this context these motor behaviors (eg, dyskinesias, as well as stereotypies, catatonic immobility, perseveration), or related experimental paradigms might be used to evaluate specificity or highlight informative underlying commonalities between RDoC domains.

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