CoActions Lab

The ability to learn and to perform structured sequences is critical in most human behaviors, such as language, music, but also in skillful movements, that make humans so distinctive. Learning those sequences relies on “chunking”, which can be viewed as two distinct processes: a first chunking operation allows you to parse the sequence into shorter clusters (as when you learn a new phone number) and is called “segmentation”. The following chunking process is named “concatenation” and consists in assembling several short chunks into longer segments. Critically, chunking makes the processing and learning of sequences more efficient. This research project aims to determine the neural correlates of chunking. Indeed, the segmentation and concatenation processes could rely on different brain structures: the former would rely on a left fronto-parietal network, including Broca’s area, whereas the latter would be performed by the basal ganglia. However, so far, these conclusions are based on correlative functional imaging data and the causal role of the basal ganglia and Broca’s area in chunking still requires further empirical validation.

Despite being one of the most common complaints expressed by patients when visiting their doctor, and having often a strong detrimental impact on the quality of life, mental fatigue remains an ill-defined and poorly understood phenomenon. Its objective evaluation in clinical practice is also very difficult because of the numerous confounding factors that can impair its assessment, e.g. simulation, depression, etc. This research project aims to understand better the fundamental cognitive and neurophysiological mechanisms that are at the origin of mental fatigue and, ultimately, to develop new ways of objectively assess mental fatigue in patients. The experiments currently underway to address more specifically the link between motivational factors and mental fatigue both in healthy subjects and in patients.

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.

When asked to define research, Nobel Prize in Physiology Dr. Albert Szent-Gyorgyi once said: ''Research is four things; Brains with which to think, eyes with which to see, machines with which to measure, and, fourth, money.'' Whilst all of these play a major role, machines and implements play key roles in sculpting (or hindering) the advancement of science. Let’s take for example the 2017 Nobel Prize in Physics. Whom would have thought that one day, it would be possible to measure distances as small as 1/1000 of an atom diameter. The same applies in the field of Neuroscience, where the constant need of both spatial and temporal resolution invites researchers to use their creativity to both improve current techniques and create new ones to further our understanding of the human brain.

In our lab, we have developped and validated a double-coil method involving transcranial magnetic stimulation over the primary motor cortex of both hemispheres, allowing one to obtain motor-evoked potentials (MEPs) in muscles of both hands at a near-simultaneous time (1 ms delay). This technique is useful in many ways. Firstly, it allows scientists to acquire double the data in the same amount of time; this is critical as it gives researchers the opportunity to test more conditions than could be done with a regular single-coil method. Secondly, obtaining MEPs in both hands within the same trial allows to investigate the distinct impact of a task on corticospinal excitability of both the dominant and non-dominant sides in the exact same setting. This increases the signal to noise ratio in a significant way. Finally, with this design, one can also make direct comparisons between MEPs elicited in the two hands on a single-trial basis. New dependent measures can be obtained, for example, indexes reflecting the difference (or ratio) between corticospinal excitability of the two hands.