4 STRATEGIC CHALLENGES:
- Decipher neural code and understand brain networks from the synapse to brain network levels
- Unravel the origin of thoughts/behavior/identity
- Tackle diseases of the nervous system through a basic /translational/clinical research coalition
- Design new generation of tools/care/personalized treatments adapted to patients with diseases of the nervous system.
To reinforce our expertise in brain development, plasticity, cellular imaging, and gene therapy, the Institute has recently recruited outstanding scientists: Bassem Hassan (Neural Development), Nicolas Renier (Structural plasticity of the nervous system), Nelson Rebola (Cellular mechanisms of sensory processes) and Nathalie Cartier (Gene Therapy)
Domains of investigation:
Molecular and cellular domain : Teams of the molecular and cellular domain are engaged in a joint and collaborative effort to understand the normal development of brain and spinal cord, and the causes of their dysfunction in aging and neurological disorders (neurodegenerative diseases, multiple sclerosis, epilepsy, brain tumors). To do so, the teams focus on:
- the study of nervous system development and the acquisition of identity, as well as structural plasticity of the adult brain
- the role of genomic regulators in the genesis of neuronal diversity, and in selective neuronal vulnerability in pathologies
- making use of, and genetically modifying, stem cells and iPS cells derived from patients and controls to build original models of pathologies, unravel mechanisms and treatments.
- the normal physiological function as well as the misfolding and propagation of proteins involved in neurodegenerative diseases.
- functional changes of cellular organelles (mitochondria, ER, endo-lysosomes, peroxysomes) and their interactions across neurodegenerative diseases, find molecular signatures associated with early pathological events.
- the contribution of the immune system, whose role is well established in multiple sclerosis, also involved at various levels in other neurodegenerative diseases and in brain tumors.
Clinical and translational domain : Advances in this domain are driven by the presence of clinicians directing, co-directing, or participating to research teams and programs, by the careful investigation of human diseases as models to better understand brain physiology or pathophysiology. Translational research at the ICM is enabled by ICM facilities combined with the proximity of the Clinical Investigation Center and the Center for Therapeutic Evaluation. The domain is developed through the following transversal activities across teams:
- establishement of well-phenotyped and biologically characterized (stratified) cohorts of patients with specific neurologic and psychiatric diseases, including rare diseases, providing opportunities for precision medicine trials.
- markers of brain activity and the modulation of brain activity through intracranial electrodes or non-invasive techniques, which widen the perspectives of intervention on patients’ symptoms.
- Development and application to translational human studies, innovative molecular imaging tools aiming at quantifying neurodegenerative mechanisms: innate immune cell activation, regenerative processes such as remyelination, energy dysregulation.
- Methodological development of tools to integrate data from various modalities to develop models of disease progression.
- Development of innovative therapeutics and molecular screening strategies through vectorization of neuroprotective molecules and genomic regulators, as well as biotherapy systems.
Cognitive neurosciences domain : The cognitive neuroscience domain in the Institute aims at providing macro-scale anatomo functional models of normal and pathological human behavior. The general objective of this domain is to build quantitative conceptual models of neural networks at the whole-brain level to explain how cognitive and emotional processes shape normal and pathological behavior in humans. The aims are:
- to uncover the cognitive and neural mechanisms underlying normal behavior,
- to understand how neurologic and psychiatric conditions alter these mechanisms.
- to develop new diagnostic, prognostic and therapeutic tools and strategies.
The main mental domains investigated by the cognitive teams include perception, attention, consciousness, self-representation, interoception, motivation, emotion, social cognition, language, decision making, executive control and behavioral adaptation, reasoning and creativity. To explore these domains, the teams combine a panel of approaches supported by ICM core facilities, and including a variety of human cognitive assessments (PRISME facility), neurophysiology and brain stimulation methods (EEG, TMS, MEG facilities), MRI neuroimaging (CENIR facility), mathematical modeling and animal models. They also explore neuropsychiatric diseases in close collaboration with the various neurological and psychiatric departments of the Pitié-Salpêtrière hospital, with a special focus on mood disorders, apathy, dementia, consciousness disorders, tumor and vascular lesions (causing aphasia, neglect and dysexecutive syndrome among others).
Neurophysiology domain : Teams in the Neurophysiology domain study brain function by measuring and manipulating physiological events related to the production and transmission of action potentials — a basic unit of communication in the brain. The goal is to understand :
- How neural and circuit activity generate normal behaviors, including sensory processing, locomotor control. To do so, the teams work at the level of individual neurons and small neural circuits, using both electrophysiological or optogenetic tools to directly observe and manipulate neural activity.
- How neural activity can lead to neurological disorders such as epilepsy, Parkinson’s disease (PD) and obsessive compulsive disorder (OCD), by using recent technological advances such as fast optical imaging and high-density electrophysiology in vivo.
The Neurophysiology domain at the ICM has developed strong links to the clinical community at the Salpêtrière hospital, including the departments of Neurology, Neurosurgery and Psychiatry. These collaborations enable several teams to perform clinical research in human patients, such as recording or manipulating brain activity in patients undergoing surgical implantation of deep brain stimulators for PD and OCD or electrodes for mapping the foci of epileptic seizures prior to resection.