BRAINBOW PROJECT - EU FET YOUNG EXPLORERS 2012-2015

Enhancing recovery of cognitive and motor functions after localized brain injuries which disrupt connections between brain and body is widely recognized as a priority in healthcare. Nowadays, neurological diseases implying severe motor impairment are among the most common causes of adult-onset disability. Millions of people worldwide are affected by paralysis, and this number is likely to increase in coming years, because of the rapidly ageing population. Current assistive technology is still limited since only a minority of survivors with hemiparesis is able to achieve independence in simple activities of daily living. The frequent lack of complete recovery makes a desirable goal the development of novel neurobiological or neurotechnological strategies for brain repair.

Over the last decade Brain-Machine Interfaces (BMIs) and generally neuro-prostheses (Nicolelis, 2003; Hochberg et al., 2006; Nicolelis & Lebedev, 2009; Hochberg et al., 2012) have been object of extensive research and may represent a valid treatment for such disabilities. The development of these devices has and will hopefully have a profound social impact on the quality of life. Nevertheless, modern neural interfaces are mainly devoted to restore lost motor functions, because of injuries at the level of the spinal cord (Collinger et al., 2012; van den Brand et al., 2012), or recover sensorial capabilities, e.g. through artificial retinal or cochlear implants (Chader et al., 2009). However, the majority of motor disabilities are caused by brain diseases, such as stroke and traumatic brain injury – TBI – (33%) and not by spinal cord injury (23%).

Only very recently scientific interest has been devoted to in vivo cognitive neural prostheses. The first ever hippocampal prosthesis improving memory function in behaving rats has been presented in recent papers (Berger et al., 2011; Berger et al., 2012). Lately the same group tested a similar device in primate prefrontal cortex aimed at restoring impaired cognitive functions (Hampson et al., 2012; Opris et al., 2012).
The realization of such prostheses implies that we know how to interact with neuronal cell assemblies, taking into account the intrinsic spontaneous activation of neuronal networks and understanding how to drive them into a desired state in order to produce a specific behaviour. The long-term goal of replacing damaged brain areas with artificial devices requires the development of neural network models to be fed with the recorded electrophysiological patterns to yield the correct brain stimulation aimed at recovering the desired functions. All these issues are extremely difficult to investigate in vivo, due to the inherent complexity and low controllability of the system. On the other hand, we believe that important insights (e.g. structure-dynamics relationship, neural coding) might be gained by using in vitro systems of increasing architectural complexity, which can be easily and wholly accessed, monitored, manipulated, and thus modelled.
This topic is extremely up-to-date and represents one of the most important challenges over the next years in terms of clinical impacts and translational medicine. This is demonstrated, not only by the literature over the past years, but also by new US funding programmes in this specific direction (see e.g. DARPA website: http://www.darpa.mil/default.aspx, programmes REPAIR and REMIND). In particular, the group of T. Berger (University of California at Irvine, CA, USA) published several papers in 2013 regarding the development of hippocampal prosthesis (both on in vitro and in vivo experimental models) for memory enhancement (Deadwyler et al., 2013; Hampson et al., 2013; Hsiao et al., 2013). On December 2013, another very interesting paper came out from the group led by R. Nudo, very active in clinical studies related to stroke and TBI (Guggenmos et al., 2013). In this paper the very first example of a unidirectional ‘neural bridge’ aimed at promoting functional connection between two motor areas (i.e. the premotor cortex and the sensory cortex) in a rat model of TBI was demonstrated. Our project BRAIN BOW is exactly along the same line, but with the goal to make even a step forward with respect to these studies: design a chip for network replacement able to operate in a closed-loop fashion. The preliminary results demonstrating that a biological network and an artificial one are able to communicate and influence, in a bi-directional way, their intrinsic dynamics, constitute one of the most promising results of the second year and represent the basis for the activities of the third and final year.

Partners: Istituto Italiano di Tecnologia (Italy), University of Genova (Italy), Tel Aviv University (Israel)