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

Cerebellar-subcortical Circuits and Alterations in Sensorimotor Dynamics

In parallel with the significant contributions to our understanding of psychosis in the context of basal ganglia circuits, cerebellar circuits are also notable in their understanding of the disease. The initial nonhuman primate literature demonstrated distinct motor and prefrontal closed-loop circuits arising from different regions of the cerebellum, via distinct thalamic nuclei. More recently, such dissociable circuits have been demonstrated in the human brain as well, using[21,22] both diffusion tensor imaging[23] and resting state functional connectivity analysis.[24,25] Dysfunction in this closed-loop circuitry could thus give rise to deficits in both the motor and cognitive domains, consistent with the deficits seen in psychosis. Indeed, the first suggestions of a role for the cerebellum in psychosis were instantiated through the cognitive dysmetria framework, wherein dysfunctional activation in cerebello-thalamo-prefrontal circuit was related to cognitive deficits.[26,27]

While the initial suggestions of a role for the cerebellum in psychosis were more cognitively focused,[28,29] more recently there has been a great deal of work in both clinical high-risk groups and patients with schizophrenia that has focused on the motor domain. With respect to its role in motor control, the cerebellum is known to be important for the smooth control and online updating of our movements. This structure allows for the use of internal models of behavior that are formed and modified through the processes of learning.[30] In psychosis, deficits in a variety of motor behaviors are present, including postural control,[31,32] motor learning,[33] and eye-blink conditioning.[34] Recently, there is also work to suggest that deficits in these domains are present in both clinical high-risk groups, as well as unaffected siblings of patients with the disease[25,35,36] suggesting that in these circuits, much like the basal ganglia circuits, motor deficits are present prior to formal disease onset, and in the absence of antipsychotic medication. Thus, they may be related to the underlying etiology of the disease. Our work[37,38] and that of others[39] has suggested that internal model deficits may contribute to the diverse symptomatology in patients with psychosis.

With the recent addition of the Motor Systems domain to the RDoC matrix, this focus on motor behavior in psychosis with respect to the cerebellum represents an interesting and important avenue of research. For example, much of the work to date with respect to postural control in psychosis can be encompassed under a proposed RDoC subconstruct covering sensorimotor dynamics. The body is reliant upon sensorimotor inputs to provide updated information about the position of the body in space. Perturbations in things like the sway area are indicative of deficits in these dynamics, and as noted, have been demonstrated in both clinical high risk and patients with schizophrenia.[32] However, other paradigms, such as sensorimotor adaptation,[40] also provide an excellent means of quantifying sensorimotor dynamics. Such paradigms have been very successful in the study of autism,[41] but have yet to be widely applied to psychosis. Further, the cerebellum and related circuits tie closely into functions that will fall under RDoC subconstructs involving inhibition and termination. Future work would greatly benefit from investigating choice reaction time paradigms, motor timing function, and stop signal reaction time with the cerebellum in mind, as suggested by the RDoC matrix. Though these tasks are well studied and characterized in healthy individuals, their application to psychosis stands to provide important new insights into cerebellar motor deficits that may also be related to broader cognitive and affective symptomatology.

Importantly, the cerebello-thalamo-motor circuits do not act in isolation. Intriguingly, and perhaps of great importance for our understanding of motor deficits in psychosis, the cerebellum and BG also share direct connections.[42,43] Thus, the anatomical connections are in place to allow for communication between these important multi-modal systems, both of which have been implicated in many of the motor deficits experienced by patients with psychosis more. While the BG loops help to select a particular action or sequence, the cerebellum works to fine tune, or add skill to these actions; these circuits work in close concert through both cortical and direct connections,[42] and it is not possible to have a comprehensive understanding of the contributions of one, without examining the other. Our group is currently at work on evaluating how overlapping and distinct areas of circuit dysfunction may provide important clues for understanding and treating psychosis. For example, it remains to be seen if unique subtypes of patients can be highlighted on the basis of particular motor behaviors (tapping into potentially different etiological pathways, and pointing to the need to employ different treatment approaches), or if patients with some motor deficits will be more likely to have other types of motor abnormalities (speaking to a more generalized dysfunction). The RDoC matrix provides a sound framework for examining these questions and further, for enriching conceptual understanding by integrating perspectives across critical systems in this population.

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