The new research team NECTARINE at INRIA in Strasbourg / France aims to create a synergy between clinicians and mathematical researchers to develop new healthcare technologies. The team works on stochastic microscopic network models to describe macroscopic experimental data, such as behavior and/or encephalographic. They collaborate closely with clinicians and choose their research focus along the clinical applications. Major scientific objectives are stochastic multi-scale simulations and mean-field descriptions of neural activity on the macroscopic scale. Moreover, merging experimental data and numerical models by machine learning techniques is an additional objective. The team's clinical research focuses on neuromodulation of patients suffering from deficits in attention and temporal prediction. The team offers the possibility to apply for a permanent position as Chargé de Recherche (CR) or Directeur de Recherche (DR) in the research field of mathematical neuroscience with a strong focus on stochastic dynamics linking brain network modelling with experimental data.

Spatial frequency domain imaging (SFDI) is a diffuse optical measurement technique that can quantify tissue optical absorption and reduced scattering on a pixel by-pixel basis. Measurements of absorption at different wavelengths enable the extraction of molar concentrations of tissue chromophores over a wide field, providing a noncontact and label-free means to assess tissue viability, oxygenation, microarchitecture, and molecular content. In this talk, I will describe openSFDI, an open-source guide for building a low-cost, small-footprint, multi-wavelength SFDI system capable of quantifying absorption and reduced scattering as well as oxyhemoglobin and deoxyhemoglobin concentrations in biological tissue. The openSFDI project has a companion website which provides a complete parts list along with detailed instructions for assembling the openSFDI system. I will also review several technological advances our lab has recently made, including the extension of SFDI to the shortwave infrared wavelength band (900-1300 nm), where water and lipids provide strong contrast. Finally, I will discuss several preclinical and clinical applications for SFDI, including applications related to cancer, dermatology, rheumatology, cardiovascular disease, and others.

We have been developing Brain-Computer Interface (BCI) using electrocorticography (ECoG) [1] , which is recorded by electrodes implanted on brain surface, and magnetoencephalography (MEG) [2] , which records the cortical activities non-invasively, for the clinical applications. The invasive BCI using ECoG has been applied for severely paralyzed patient to restore the communication and motor function. The non-invasive BCI using MEG has been applied as a neurofeedback tool to modulate some pathological neural activities to treat some neuropsychiatric disorders. Although these techniques have been developed for clinical application, BCI is also an important tool to investigate neural function. For example, motor BCI records some neural activities in a part of the motor cortex to generate some movements of external devices. Although our motor system consists of complex system including motor cortex, basal ganglia, cerebellum, spinal cord and muscles, the BCI affords us to simplify the motor system with exactly known inputs, outputs and the relation of them. We can investigate the motor system by manipulating the parameters in BCI system. Recently, we are developing some BCIs to visualize and manipulate our perception and mental imagery. Although these BCI has been developed for clinical application, the BCI will be useful to understand our neural system to generate the perception and imagery. In this talk, I will introduce our study of phantom limb pain [3] , that is controlled by MEG-BCI, and the development of a communication BCI using ECoG [4] , that enable the subject to visualize the contents of their mental imagery. And I would like to discuss how much we can control our cortical activities that represent our perception and mental imagery. These examples demonstrate that BCI is a promising tool to visualize and manipulate the perception and imagery and to understand our consciousness. References 1. Yanagisawa, T., Hirata, M., Saitoh, Y., Kishima, H., Matsushita, K., Goto, T., Fukuma, R., Yokoi, H., Kamitani, Y., and Yoshimine, T. (2012). Electrocorticographic control of a prosthetic arm in paralyzed patients. AnnNeurol 71, 353-361. 2. Yanagisawa, T., Fukuma, R., Seymour, B., Hosomi, K., Kishima, H., Shimizu, T., Yokoi, H., Hirata, M., Yoshimine, T., Kamitani, Y., et al. (2016). Induced sensorimotor brain plasticity controls pain in phantom limb patients. Nature communications 7, 13209. 3. Yanagisawa, T., Fukuma, R., Seymour, B., Tanaka, M., Hosomi, K., Yamashita, O., Kishima, H., Kamitani, Y., and Saitoh, Y. (2020). BCI training to move a virtual hand reduces phantom limb pain: A randomized crossover trial. Neurology 95, e417-e426. 4. Ryohei Fukuma, Takufumi Yanagisawa, Shinji Nishimoto, Hidenori Sugano, Kentaro Tamura, Shota Yamamoto, Yasushi Iimura, Yuya Fujita, Satoru Oshino, Naoki Tani, Naoko Koide-Majima, Yukiyasu Kamitani, Haruhiko Kishima (2022). Voluntary control of semantic neural representations by imagery with conflicting visual stimulation. arXiv arXiv:2112.01223.

Over the last few decades, the use of deep brain stimulation (DBS) to improve the treatment of those with neurological movement disorders represents a critical success story in the development of invasive neurotechnology and the promise of brain-computer interfaces (BCI) to improve the lives of those suffering from incurable neurological disorders. In the last decade, investigational devices capable of recording and streaming neural activity from chronically implanted therapeutic electrodes has supercharged research into clinical applications of BCI, enabling in-human studies investigating the use of adaptive stimulation algorithms to further enhance therapeutic outcomes and improve future device performance. In this talk, Dr. Herron will review ongoing clinical research efforts in the field of adaptive DBS systems and algorithms. This will include an overview of DBS in current clinical practice, the development of bidirectional clinical-use research platforms, ongoing algorithm evaluation efforts, a discussion of current adoption barriers to be addressed in future work.

The cognitive neuroscience of conscious perception has seen considerable growth over the past few decades. Confirming an influential hypothesis driven by earlier studies of neuropsychological patients, we have found that the lateral and polar prefrontal cortices play important causal roles in the generation of subjective experiences. However, this basic empirical finding has been hotly contested by researchers with different theoretical commitments, and the differences are at times difficult to resolve. To address the controversies, I suggest one alternative venue may be to look for clinical applications derived from current theories. I outline an example in which we used closed-loop fMRI combined with machine learning to nonconsciously manipulate the physiological responses to threatening stimuli, such as spiders or snakes. A clinical trial involving patients with phobia is currently taking place. I also outline how this theoretical framework may be extended to other diseases. Ultimately, a truly meaningful understanding of the fundamental nature of our mental existence should lead to useful insights for our colleagues on the clinical frontlines. If we use this as a yardstick, whoever loses the esoteric theoretical debates, both science and the patients will always win.

This seminar is part of our “Emergent Scientists” series, an initiative that provides a platform for scientists at the critical PhD/postdoc transition period to share their work with a broad audience and network. Summary: These talks cover Alzheimer’s disease (AD) research in both mice and humans. Christiana will discuss in particular the translational aspects of applying mouse work to humans and the importance of timing in disease pathology and intervention (e.g. timing between AD biomarkers vs. symptom onset, timing of therapy, etc.). Siddharth will discuss a rare variant of Alzheimer’s disease called “Logopenic Progressive Aphasia”, which presents with temporo-parietal atrophy yet relative sparing of hippocampal circuitry. Siddharth will discuss how, despite the unusual anatomical basis underlying this AD variant, degeneration of the angular gyrus in the left inferior parietal lobule contributes to memory deficits similar to those of typical amnesic Alzheimer’s disease. Christiana’s abstract: Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder that causes severe deterioration of memory, cognition, behavior, and the ability to perform daily activities. The disease is characterized by the accumulation of two proteins in fibrillar form; Amyloid-β forms fibrils that accumulate as extracellular plaques while tau fibrils form intracellular tangles. Here we aim to translate findings from a commonly used AD mouse model to AD patients. Here we initiate and chronically inhibit neuropathology in lateral entorhinal cortex (LEC) layer two neurons in an AD mouse model. This is achieved by over-expressing P301L tau virally and chronically activating hM4Di DREADDs intracranially using the ligand dechloroclozapine. Biomarkers in cerebrospinal fluid (CSF) is measured longitudinally in the model using microdialysis, and we use this same system to intracranially administer drugs aimed at halting AD-related neuropathology. The models are additionally tested in a novel contextual memory task. Preliminary findings indicate that viral injections of P301L tau into LEC layer two reveal direct projections between this region and the outer molecular layer of dentate gyrus and the rest of hippocampus. Additionally, phosphorylated tau co-localize with ‘starter cells’ and appear to spread from the injection site. Preliminary microdialysis results suggest that the concentrations of CSF amyloid-β and tau proteins mirror changes observed along the disease cascade in patients. The disease-modifying drugs appear to halt neuropathological development in this preclincial model. These findings will lead to a novel platform for translational AD research, linking the extensive research done in rodents to clinical applications. Siddharth’s abstract: A distributed brain network supports our ability to remember past events. The parietal cortex is a critical member of this network, yet, its exact contributions to episodic remembering remain unclear. Neurodegenerative syndromes affecting the posterior neocortex offer a unique opportunity to understand the importance and role of parietal regions to episodic memory. In this talk, I introduce and explore the rare neurodegenerative syndrome of Logopenic Progressive Aphasia (LPA), an aphasic variant of Alzheimer’s disease presenting with early, left-lateralized temporo-parietal atrophy, amidst relatively spared hippocampal integrity. I then discuss two key studies from my recent Ph.D. work showcasing pervasive episodic and autobiographical memory dysfunction in LPA, to a level comparable to typical, amnesic Alzheimer’s disease. Using multimodal neuroimaging, I demonstrate how degeneration of the angular gyrus in the left inferior parietal lobule, and its structural connections to the hippocampus, contribute to amnesic profiles in this syndrome. I finally evaluate these findings in the context of memory profiles in other posterior cortical neurodegenerative syndromes as well as recent theoretical models underscoring the importance of the parietal cortex in the integration and representation of episodic contextual information.