Make a Left Turn: Cortico-Striatal Circuitry Mediating the Attentional Control of Complex Movements

Background In movement disorders such as Parkinson's disease (PD), cholinergic signaling is disrupted by the loss of basal forebrain cholinergic neurons, as well as aberrant activity in striatal cholinergic interneurons (ChIs). Several lines of evidence suggest that gait imbalance, a key disabling symptom of PD, may be driven by alterations in high-level frontal cortical and cortico-striatal processing more typically associated with cognitive dysfunction. Methods Here we describe the corticostriatal circuitry that mediates the cognitive-motor interactions underlying such complex movement control. The ability to navigate dynamic, obstacle-rich environments requires the continuous integration of information about the environment with movement selection and sequencing. The cortical-attentional processing of extero- and interoceptive cues requires modulation by cholinergic activity to guide striatal movement control. Cue-derived information is transferred to striatal circuitry primarily via fronto-striatal glutamatergic projections. Result Evidence from parkinsonian fallers and from a rodent model reproducing the dual cholinergic-dopaminergic losses observed in these patients supports the main hypotheses derived from this neuronal circuitry-guided conceptualization of parkinsonian falls. Furthermore, in the striatum, ChIs constitute a particularly critical node for the integration of cortical with midbrain dopaminergic afferents and thus for cues to control movements. Conclusion Procholinergic treatments that enhance or rescue cortical and striatal mechanisms may improve complex movement control in parkinsonian fallers and perhaps also in older persons suffering from gait disorders and a propensity for falls. (c) 2021 International Parkinson and Movement Disorder Society

Automated summary

In movement disorders such as Parkinson's disease, disruptions in cholinergic signaling and aberrant activity in striatal cholinergic interneurons may contribute to gait imbalance. The integration of cortical and striatal mechanisms guided by cholinergic activity plays a critical role in complex movement control in parkinsonian fallers and older individuals with gait disorders.