LINKERS · Locomotor issues in Parkinsonian's Mesencephalic Locomotor Region and Subthalamic nucleus

Locomotor issues in Parkinsonian's Mesencephalic Locomotor Region and Subthalamic nucleus

Idiopathic Parkinson disease (PD) affects 1–2 per 1000 of the population at any time and its prevalence is increasing with age to affect 1% of the population above 60 years. Due to a dopaminergic depletion, PD impacts motor function and is characterized by bradykinesia, rigidity and resting tremor. Furthermore, as long the disease progresses axial symptoms appear such as gait disorders, falls and freezing of gait episodes. PD does not decrease life expectancy but have an important impact on the quality of life. Accordingly, and due to an ageing of the population, both the number of PD patients and the burden on the social healthcare systems will increase. If dopamine supplementation is useful at early stage of the disease, it leads to dyskinesia and motor fluctuations in addition with dopa resistant symptoms declared in later stage of the disease. Among available treatment, Deep brain stimulation (DBS) via the implantation of electrodes has been pushed forward to, both, alleviate dopa-resistant signs and enhance dopaminergic treatment effects. However, literature is sparse, and some discrepancy exists in the literature in terms of population and brain area to target. Since Freezing of gait (FOG) and falls worsen over time and represent the dominant motor disabilities in advanced Parkinson’s, we developed a program aimed to record neuronal activity during walking and examine the role of both brain structures (i.e., the subthalamic nucleus (STN) and mesencephalic locomotor region (MLR)) known to be involved in the regulation of gait pattern in human. Our objectives were two-folds: 1- Characterize neuronal activity of the STN and MLR during initiation and termination of walking, free walking and walking with motor or cognitive load, before and during half-turn. 2- Determine the relationship between STN and MLR neuronal activities and walking performance (measured using specific kinetic and kinematic parameters, as well as the occurrence of FOG episodes) This program is important for society since ameliorating PD treatment and alleviating symptoms will ameliorate the quality of life of PD patients and will decrease the burden on public health costs. As conclusions, this program showed in implanted parkinsonians that suffer from gait disorders several specific modulations of the neural activity in different frequency band known to be involved in the production of movement and the cognitive engagement in a motor task respectively. These modulations were present in both structures but differently modulated during gait events or during an increase in the cognitive involvement in the task. This project also allowed to gain insight in the neural signature of the Parkinson’s disease. Conversely, we demonstrated that DBS was not as effective in both structures to alleviate postural and gait disorders. Finally, this program also participates to decipher the circuitry of the basal ganglia an important but poorly studied network in the brainstem.

Data: CORDIS, © European Union