Combining BMI Stimulation and Mathematical Modeling for Acute Stroke Recovery and Neural Repair

Abstract

Rehabilitation is a neural plasticity-exploiting approach that forces undamaged neural circuits to undertake the functionality of other circuits damaged by stroke. It aims to partial restoration of the neural functions by circuit remodeling rather than by the regeneration of damaged circuits. The core hypothesis of the present paper is that - in stroke - brain machine interfaces (BMIs) can be designed to target neural repair instead of rehabilitation. To support this hypothesis we first review existing evidence on the role of endogenous or externally applied electric fields on all processes involved in CNS repair. We then describe our own results to illustrate the neuroprotective and neuroregenerative effects of BMI-electrical stimulation on sensory deprivation-related degenerative processes of the CNS. Finally, we discuss three of the crucial issues involved in the design of neural repair-oriented BMIs: when to stimulate, where to stimulate and - the particularly important but unsolved issue of - how to stimulate. We argue that optimal parameters for the electrical stimulation can be determined from studying and modeling the dynamics of the electric fields that naturally emerge at the central and peripheral nervous system during spontaneous healing in both, experimental animals and human patients. We conclude that a closed-loop BMI that defines the optimal stimulation parameters from a priori developed experimental models of the dynamics of spontaneous repair and the on-line monitoring of neural activity might place BMIs as an alternative or complement to stem-cell transplantation or pharmacological approaches, intensively pursued nowadays.

Keywords: neuroprostheses; neuroprotection; peripheral nerve; plasticity; rat; trigeminal.

Figure 1

Schematic diagram of the experimental procedure. Unilateral section of the sensory trigeminal nerve (A); implant of a stimulation device in half of the animals and 4-weeks artificial stimulation of the nervous system (B); sections and histochemistry (C) histological, stereological study of the brains (D).

Figure 2

Photomicrographs of cytochrome oxidase (CyO)-stained horizontal sections of rat somatosensory cortices at the level of the barrel field. They correspond to animals with unilateral lesions of the trigeminal nerve [input-deprivation of the contralateral somatosensory cortex – sections in (a,c)] and animals with identical lesions but with subsequent artificial stimulation by means of an external device [BMI input to the contralateral cortex – sections in (b,d)]. Brain hemispheres receiving input from non-manipulated nerves (control) are left and experimentally affected are right. Asterisk in [a] points to a single barrel of the fourth cortical layer. Animals with nerve lesions show a lower intensity of CyO-staining in the affected hemisphere [b] indicating the lower activity of the affected somatosensory cortex in comparison to the control one [b]. Artificial stimulation has a net positive effect to the affected cortex and maintains the neural activity to a normal level as proved by the similar staining intensities in the cortexes of BMI-animals [b,d]. Original magnifications 20×.