Evaluating the impact of intracortical microstimulation on distant cortical brain regions for neuroprosthetic applications

Enhancing functional motor recovery after localized brain injury is a widely recognized priority in healthcare as disorders of the nervous system that cause motor impairment, such as stroke, are among the most common causes of adult-onset disability. Restoring physiological function in a dysfunctional brain to improve quality of life is a primary challenge in scientific and clinical research and could be driven by innovative therapeutic approaches. Recently, techniques using brain stimulation methodologies have been employed to promote post-injury neuroplasticity for the restitution of motor function. One type of closed-loop stimulation, i.e., activity-dependent stimulation (ADS), has been shown to modify existing functional connectivity within either healthy or injured cerebral cortices and used to increase behavioral recovery following cortical injury. The aim of this PhD thesis is to characterize the electrophysiological correlates of such behavioral recovery in both healthy and injured cortical networks using in vivo animal models. We tested the ability of two different intracortical micro-stimulation protocols, i.e., ADS and its randomized open-loop version (RS), to potentiate cortico-cortical connections between two distant cortical locations in both anaesthetized and awake behaving rats. Thus, this dissertation has the following three main goals: 1) to investigate the ability of ADS to induce changes in intra-cortical activity in healthy anesthetized rats, 2) to characterize the electrophysiological signs of brain injury and evaluate the capability of ADS to promote electrophysiological changes in the damaged network, and 3) to investigate the long-term effects of stimulation by repeating the treatment for 21 consecutive days in healthy awake behaving animals. The results of this study indicate that closed-loop activity-dependent stimulation induced greater changes than open-loop random stimulation, further strengthening the idea that Hebbian-inspired protocols might potentiate cortico-cortical connections between distant brain areas. The implications of these results have the potential to lead to novel treatments for various neurological diseases and disorders and inspire new neurorehabilitation therapies

Nonlinear dynamical modeling of human hippocampal CA3-CA1 functional connectivity for memory prostheses

This paper reports the first nonlinear dynamical model of human hippocampus for building memory prostheses. In this study, spike trains are recorded from the hippocampal CA3 and CA1 regions in epileptic patients performing two memory-dependent behavioral tasks. Using CA3 and CA1 spike trains as inputs and outputs respectively, second-order generalized Laguerre-Volterra models are built to capture the nonlinear dynamics underlying the spike train transformations. These models can predict the CA1 spike trains based on the CA3 spike train and thus be used as the computational basis of the hippocampal memory prosthesis

Augmentation of Brain Function: Facts, Fiction and Controversy. Volume II: Neurostimulation and Pharmacological Approaches

The Volume II is entitled “Neurostimulation and pharmacological approaches”. This volume describes augmentation approaches, where improvements in brain functions are achieved by modulation of brain circuits with electrical or optical stimulation, or pharmacological agents. Activation of brain circuits with electrical currents is a conventional approach that includes such methods as (i) intracortical microstimulation (ICMS), (ii) transcranial direct current stimulation (tDCS), and (iii) transcranial magnetic stimulation (TMS). tDCS and TMS are often regarded as noninvasive methods. Yet, they may induce long-lasting plastic changes in the brain. This is why some authors consider the term “noninvasive” misleading when used to describe these and other techniques, such as stimulation with transcranial lasers. The volume further discusses the potential of neurostimulation as a research tool in the studies of perception, cognition and behavior. Additionally, a notion is expressed that brain augmentation with stimulation cannot be described as a net zero sum proposition, where brain resources are reallocated in such a way that gains in one function are balanced by costs elsewhere. In recent years, optogenetic methods have received an increased attention, and several articles in Volume II cover different aspects of this technique. While new optogenetic methods are being developed, the classical electrical stimulation has already been utilized in many clinically relevant applications, like the vestibular implant and tactile neuroprosthesis that utilizes ICMS. As a peculiar usage of neurostimulation and pharmacological methods, Volume II includes several articles on augmented memory. Memory prostheses are a popular recent development in the stimulation-based BMIs. For example, in a hippocampal memory prosthesis, memory content is extracted from hippocampal activity using a multiple-input, multiple-output non-linear dynamical model. As to the pharmacological approaches to augmenting memory and cognition, the pros and cons of using nootropic drugs are discussed