Translational Model of Cortical Premotor-Motor Networks.

Deciphering the physiological patterns of motor network connectivity is a prerequisite to elucidate aberrant oscillatory transformations and elaborate robust translational models of movement disorders. In the proposed translational approach, we studied the connectivity between premotor (PMC) and primary motor cortex (M1) by recording high-density electroencephalography in humans and between caudal (CFA) and rostral forelimb (RFA) areas by recording multi-site extracellular activity in mice to obtain spectral power, functional and effective connectivity. We identified a significantly higher spectral power in ß- and γ-bands in M1compared to PMC and similarly in mice CFA layers (L) 2/3 and 5 compared to RFA. We found a strong functional ß-band connectivity between PMC and M1 in humans and between CFA L6 and RFA L5 in mice. We observed that in both humans and mice the direction of information flow mediated by ß- and γ-band oscillations was predominantly from PMC toward M1 and from RFA to CFA, respectively. Combining spectral power, functional and effective connectivity, we revealed clear similarities between human PMC-M1 connections and mice RFA-CFA network. We propose that reciprocal connectivity of mice RFA-CFA circuitry presents a suitable model for analysis of motor control and physiological PMC-M1 functioning or pathological transformations within this network.

Subthalamic stimulation modulates context-dependent effects of beta bursts during fine motor control.

Increasing evidence suggests a considerable role of pre-movement beta bursts for motor control and its impairment in Parkinson's disease. However, whether beta bursts occur during precise and prolonged movements and if they affect fine motor control remains unclear. To investigate the role of within-movement beta bursts for fine motor control, we here combine invasive electrophysiological recordings and clinical deep brain stimulation in the subthalamic nucleus in 19 patients with Parkinson's disease performing a context-varying task that comprised template-guided and free spiral drawing. We determined beta bursts in narrow frequency bands around patient-specific peaks and assessed burst amplitude, duration, and their immediate impact on drawing speed. We reveal that beta bursts occur during the execution of drawing movements with reduced duration and amplitude in comparison to rest. Exclusively when drawing freely, they parallel reductions in acceleration. Deep brain stimulation increases the acceleration around beta bursts in addition to a general increase in drawing velocity and improvements of clinical function. These results provide evidence for a diverse and task-specific role of subthalamic beta bursts for fine motor control in Parkinson's disease; suggesting that pathological beta bursts act in a context dependent manner, which can be targeted by clinical deep brain stimulation.

Translating Pathological Brain Activity Primers in Parkinson's Disease Research.

Translational experimental approaches that help us better trace Parkinson's disease (PD) pathophysiological mechanisms leading to new therapeutic targets are urgently needed. In this article, we review recent experimental and clinical studies addressing abnormal neuronal activity and pathological network oscillations, as well as their underlying mechanisms and modulation. Our aim is to enhance our knowledge about the progression of Parkinson's disease pathology and the timing of its symptom's manifestation. Here, we present mechanistic insights relevant for the generation of aberrant oscillatory activity within the cortico-basal ganglia circuits. We summarize recent achievements extrapolated from available PD animal models, discuss their advantages and limitations, debate on their differential applicability, and suggest approaches for transferring knowledge on disease pathology into future research and clinical applications.