Motor system dysfunction in the schizophrenia diathesis: Neural systems to neurotransmitters

Abstract

Motor control is a ubiquitous aspect of human function, and from its earliest origins, abnormal motor control has been proposed as being central to schizophrenia. The neurobiological architecture of the motor system is well understood in primates and involves cortical and sub-cortical components including the primary motor cortex, supplementary motor area, dorsal anterior cingulate cortex, the prefrontal cortex, the basal ganglia, and cerebellum. Notably all of these regions are associated in some manner to the pathophysiology of schizophrenia. At the molecular scale, both dopamine and γ-Aminobutyric Acid (GABA) abnormalities have been associated with working memory dysfunction, but particularly relating to the basal ganglia and the prefrontal cortex respectively. As evidence from multiple scales (behavioral, regional and molecular) converges, here we provide a synthesis of the bio-behavioral relevance of motor dysfunction in schizophrenia, and its consistency across scales. We believe that the selective compendium we provide can supplement calls arguing for renewed interest in studying the motor system in schizophrenia. We believe that in addition to being a highly relevant target for the study of schizophrenia related pathways in the brain, such focus provides tractable behavioral probes for in vivo imaging studies in the illness. Our assessment is that the motor system is a highly valuable research domain for the study of schizophrenia.

Keywords: Dopamine; Motor Cortex; Motor Dysfunction; Schizophrenia.

Figure 1

The figure provides a schematic depiction of motor, cingulate and cerebellar regions and their role in aspects of motor behavior. Highlighted are M1: Primary Motor Cortex, SMA: Supplementary Motor Area, Pre-SMA: Pre-Supplementary Motor Area, dACC: Dorsal Anterior Cingulate Cortex, Basal Ganglia, and Cerebellum. The corresponding text boxes summarize known aspects of the relative specialization of function of the regions.

Figure 2

Figure 1 is adapted to summarize some of the known findings in schizophrenia. As seen in the text boxes (and more extensively discussed in the text), regions central to motor behavior also are characterized by widespread and multifaceted abnormalities in schizophrenia. These include abnormal structure (at multiple scales) and aberrant responses during motor tasks. The color and naming schemes are maintained from Figure 1.

Figure 3

A summary of dopamine projections and implications for schizophrenia. The nigrostriatal dopaminergic projection system originates from the substantia nigra (SN), whereas the mesocortical dopaminergic projection system originates from the ventral tegmental area (VTA). These systems project to the basal ganglia, and the motor and cingulate regions respectively (see marked projections). The text boxes summarize evidence of dysfunction in schizophrenia. The color and naming schemes are consistent with previous figures.