Institut Cerveau et Santé Mentale

WP1 : CESAME Institute includes 5 technological platforms coordinated by the Neurodis Foundation. Neurodis was in charge of the project administration (convention, amendments, consortium agreement, governance…). The foundation helps the partners with all changes and we promote CESAME to develop new partnerships (presentations in congresses, inaugurations…).

WP2 cell engineering : The cell-engineering platform has generated a panel of novel pluripotent stem cell lines (both embryonic stem cells and induced pluripotent stem cells) in rabbits, human, and rhesus monkey. These new cell lines are useful to study the molecular mechanisms of pluripotency in mammals and to design cell and organ therapy. Given their potential in differentiating in the neuroglial lineages, these cell lines provide invaluable tools for studying the early steps of the molecular and cellular development of the cerebral cortex in human and non human primates

WP2 optogenetics : The challenge here was to achieve gene transfer in the non-human primate model and obtain statistically significant effects on measures of neuronal activity and behavior in response to optogenetic stimulation. Stimulation tests are currently performed on a pilot animal, which has been transfected with an AAV plasmid containing the ChannelRhodopsin within the striatum. Another animal will be enrolled. Preliminary results obtained by electrophysiological recordings indicate that the optic stimulation can drive activity of striatal cells. We will pursue this optogenetic work and adapt our strategies depending on our future results.

WP3 : The Blood-brain interface exploration platform aims at developing methodologies to achieve a real breakthrough on blood-brain barrier (BBB) research. The facility developed new cellular models of blood-brain interfaces, designed methods to study transport and cell migration across the barriers in developing animals, and applications of these cellular models and transport methods for pathophysiological and drug delivery investigations. It also developed in collaboration with Cynbiose an interface tissue bank from non-human primate available for research studies. The facility is open for service and research contract with public and private laboratories.

WP4 : The Human intracerebral EEG signal platform has two main usage: the pre-surgical investigation defining the target of the epilepsy surgery procedure (139 from 2014 to june 2018) and research on the large-scale neural dynamics of Human Cognition, through cognitive paradigms performed by patients implanted with iEEG electrodes

Since the finalization of the set-up in 2013, the capacity for iEEG investigation has doubled with the opening of a new laboratory open in January 2014 thanks to the IHU. The protocols are now done in the laboratory each time it is possible. More than 100 patients have been evaluated by one or more of the 66 protocols performed in the iEEG platform over the period of the IHU. Regarding micro-electrode recordings, the Faraday cage, the specific set-up using Blackrock system and the DIXI micro/macro electrodes are fully available since march 2018. Three patients have already been investigated using this novel technique and, thanks to the IHU, 18 others will be investigated over the next 3 years.

WP5 : Neuro-immersion (N-I) is a visionary platform devoted to the study of the brain and the treatment of neurological and psychiatric deficits. It combines multisensory virtual reality, electrophysiological recordings and neurostimulation to study normal brain functions and develop innovative therapies. All the foreseen equipment is now available to the academic and private communities. Currently and till the end of 2019 the staff (AI, IE) is funded from external resources, we need hiring a permanent position (IE) for the survival of the platform. The Neuro-immersion platform (N-i) has been created ex novo. Objectives fully achieved.

WP6 : Neuro-imaging facility offers access to an operational simultaneous MRI-PET scanner, equipped for experimentation. CESAME contributes to the platform in terms of radiochemistry and human resources. Sustained by more than 30 identified projects, the aim of the PET-MRI was to explore essential functions of the central nervous system in the normal and pathological brain. The projects carried over by the MRI-PET scanner totally benefit from the combination of the MRI and the PET. Beyond the gain in comfort and speed of realization, these protocols benefit from the simultaneous acquisition of the two modalities, which is fundamental and unexplored to date. Main explorations have been processed in the following domains: cognition, neurovascular diseases, brain cancer, coma, effects of the transcranial direct current stimulation. 

In clinical neurology main projects aimed at characterizing the risk of atheroma plaques, predicting the outcome of coma, characterising pituitary microen adenomas before surgical therapeutic management of patients with Cusching disease. Neuroscientific projects also aimed at looking at the effects of transcranial direct current stimulation (TDCS) on the dopaminergic system through PET, and induced changes in neuronal activity thanks to MRI, exploring the relationship between serotonin transporter and cerebral activities associated with the perception of social dominance. Through  preclinical studies more fundamental aspect of brain disease were explored: functional characterization of biased agonist of the serotoninergic neurotransmission system, developing the imaging of translational inflammation with MRI-PET in human primates (PNH), in a cyclosporine A-treated stroke model, validation of an MRO-based OEF / CMRO2 cartography using gold standard PET methods ([15O]H2O for blood flow, and [15O]O2 gas for oxygen consumption) in a non-human primate (NHP) model of focal cerebral ischemia, exploring the neural circuits involved in food intake and control of anxiety states. It may extend beyond anorexia, affect other psychiatric disorders that express eating disorders or anxiety disorders for whom the serotonergic system is also a therapeutic target. Twenty other research projects are being prepared for a start in 2017, 2018 and 2019.

The projects carried over by the MRI-PET scanner totally benefit from the combination of the MRI and the PET. Beyond the gain in comfort and speed of realization, these protocols benefit from the simultaneous acquisition of the two modalities, which is fundamental and unexplored to date.

Apart but related to applications, projects aimed at developing radiopharmaceutical potential of PET imaging combined with MRI. With the development of models for new tracers of the noradrenergic system ([¹¹C]Yohimbine). The developed projects address new methodological issues related to quantification and to the respective contributions of MRI or PET information for a reciprocal improvement of the signals of the two modalities. Use of MRI Information to correct PET for brain attenuation, Measurement of the input function on the image using MRI for brain PET dynamic modelling, Head motion correction, PET image correction with resolution recovery and noise reduction including a Monte-Carlo simulator, Development of good manufacturing practice (GMP) for radiotracer production capacity and pharmacokinetic testing combined with a pharmacological approach BOLD MRI.