Parkinson
Parkinson’s disease (PD) is currently the second most frequent neurodegenerative disease in the world. Since its first risk factor is age, the frequency of this disease is expected to rise even more in the future, due to the aging of the world’s population.
PD results from an alteration in the functioning of the basal ganglia (BG), mainly due to the early degeneration of a cerebral region involved in the production of dopamine – the Substantia Nigra pars compacta (SNc) – a very important neurotransmitter in the brain. The exact causes of this degeneration have not been elucidated yet. Hence, treatments remain purely symptomatic; to date, neuroprotective interventions able to slow down the evolution of the disease are not available for patients.
Since PD is characterized by a slowing of movements, we are currently investigating motor inhibitory influences during the preparation of actions using transcranial magnetic stimulation (TMS) in this population of patients. We study the role of the subthalamic nucleus (STN) by assessing motor inhibition in patients treated with deep brain stimulation of STN. This project could on the long term benefit all patients suffering from diseases characterized by excessive impulsivity (addictions, OCDs, ADHD…).
Furthermore, we also try to comprehend deficits like slowness found in PD from a more fundamental point of view, which is: a dysfunction of decision making processes. To do so, neuronal STN activity is recorded in PD patients while they perform reward- and effort-based decision making tasks. Another way to approach this question is to modulate levels of dopamine in healthy subjects, in order to see how this neurotransmitter determines the ratio between the value of the reward associated with an action and the effort invested in order to obtain it.
Furthermore, action selection involves a tight balance between the competing demands of decision speed and accuracy. Recent work suggests that this balance is adjusted by an urgency signal that operates as a modulator of neural gain, boosting motor activity when speed is of essence and reducing it when the focus is on accuracy. The motor neural signature of this signal seems global (non-specific), although this point requires further support. In addition, little is known about the neural source of the urgency signal. We currently test the hypothesis that urgency is implemented by a modulation of the strength of global motor suppression mediated by the STN.
Finally, since dopamine is not the only neurotransmitter to be affected in PD, we are also interested in the study of the link between the degeneration of the noradrenergic system and the fatigue symptoms in PD patients. The latter – although possibly being very disabling – are poorly controlled by common treatment. Hence, our findings could orient treatments towards noradrenaline, in order to better help the patients in the future.
People involved:
- From the lab: Benoit CE, Derosiere G, Duque J, Solopchuk O, Wilhelm E
- Alumni: Zénon A
- Collaborators: Jeanjean A, Raftopoulos C, Zénon A
Related publications:
- Zénon A, Duclos Y, Carron R, Witjas T, Baunez C, Régis J, Azulay JP, Brown P, Eusebio A. The human subthalamic nucleus encodes the subjective value of reward and the cost of effort during decision-making. Brain. 2016; 139(Pt 6): 1830-43.
- Zénon A, Devesse S, Olivier E. Dopamine Manipulation Affects Response Vigor Independently of Opportunity Cost. J Neurosci. 2016; 36(37): 9516-25.
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