Altered Functional Segregated Sensorimotor, Associative, and Limbic Cortical-Striatal Connections in Parkinson's Disease: An fMRI Investigation

Multiple studies have identified segregated functional territories in the basal ganglia for the control of goal-directed and habitual actions. It has been suggested that in PD, preferential loss of dopamine in the posterior putamen may cause a major deficit in habitual control (mediated by the sensorimotor cortical-striatal loop), and the patients may therefore be forced into a progressive reliance on the goal-directed behavior (regulated by the associative cortical-striatal loop). Functional evidence supporting this point is scarce at present. This study aims to verify the functional connectivity changes within the sensorimotor, associative, and limbic cortical-striatal loops in PD. Resting-state fMRI of 70 PD patients and 30 controls were collected. Bilateral tripartite functional territories of basal ganglia and their associated cortical structures were chosen as regions of interest, including ventral striatum and ventromedial prefrontal cortex for limbic loop; dorsomedial striatum and dorsolateral prefrontal cortex for associative loop; dorsolateral striatum and sensorimotor cortex for sensorimotor loop. Pearson's correlation coefficients for each seed pair were calculated to obtain the functional connectivity. The relationships between functional connectivity and disease severity were further investigated. Functional connectivity between dorsolateral striatum and sensorimotor cortex is decreased in PD patients, and negatively correlated with disease duration; whereas functional connectivity between dorsomedial striatum and dorsolateral prefrontal cortex is also decreased but postitively correlated with disease duration. The functional connectivity within the sensorimotor loop is pathologically decreased in PD, while the altered connectivity within the associative loop may indicate a failed attempt to compensate for the loss of connectivity within the sensorimotor loop.

COMPARISON OF THEORIES OF REST TREMOR MECHANISM IN PARKINSON’S DISEASE: CENTRAL OSCILLATOR (SOURCE-TRIGGERED OSCILLATIONS) AND FEEDBACK-INDUCED INSTABILITY IN THE SENSORIMOTOR LOOP (SELF-SUSTAINED OSCILLATIONS)

Rest tremor is one of the most common and disabling symptoms of Parkinson’s disease (PD). The exact neural origin of rest tremor is still not clearly understood. Understanding the origin of rest tremor is important as it may aid in optimizing existing treatment strategies such as Deep Brain Stimulation or in developing new treatment strategies for rest tremor reduction. There are broadly two theories that are gaining prominence for rest tremor generation in PD. The first theory is the central oscillator theory that states that the rest tremor is triggered by an oscillatory source in the brain. The second theory is the feedback-induced instability theory that states that the rest tremor arises out of a feedback-induced instability in the sensorimotor loop. This paper analyzes validity of the two theories based on established clinical observations of Parkinsonian rest tremor by using representative simulation examples. Finally, based on our analysis, we propose two test-worthy experiments for further validation.