Prospect of brain-machine interface in motor disabilities: the future support for multiple sclerosis patient to improve quality of life

Abstract

Multiple sclerosis (MS) is an autoimmune neurological disorder, which has impacted health related quality of life (HRQoL) more intensively than any other neurological disorder. The approaches to improve the health standard in MS patient are still a subject of primary importance in medical practice and seek a lot of experimental exploration. The present review briefly explains the anomaly in neuron anatomy and dysfunction in signal transmission arising in the context with the chronic cerebrospinal venous insufficiency (CCSVI), a recent hypothesis related with MS pathophysiology. Subsequently, it insights brain-machine interface (BMI) as an alternative approach to improve the HRQoL of MS subjects. Information sources were searched from peer-reviewed data bases (Medline, BioMed Central, PubMed) and grey-literature databases for data published in 2000 or later. We also did systemic search in edited books, articles in seminar papers, reports extracted from newspapers and scientific magazines, articles accessed from internet; mostly using PubMed, Google search engine and Wikipedia. Out of approximately 178, 240 research articles obtained using selected keywords, those articles were included in the present study which addresses the latest definitions of HRQol and latest scientific and ethical developments in the research of MS and BMI. The article presented a brief survey of CCSVI mediated MS and BMI-approach as a treatment to serve the patients suffering from disabilities as a result of MS, followed by successful precedence of BMI approach. Apart from these, the major findings of selected research articles including the development of parameters to define HRQoL, types and development of BMIs and its role in interconnecting brain with actuators, along with CCSVI being a possible cause of MS have formed the foundations to conclude the findings of the present review article. We propose a perspective BMI approach and promises it holds for future research to improve HRQoL in MS patients. In addition, we propose that brain-computer interfaces will be the core of new treatment modalities in the future for MS disabilities.

Keywords: Blood brain barrier; Brain-machine interface; Chronic cerebrospinal venous insufficiency; Immunomodulation; Multiple sclerosis.

Figure 1

Illustration of neuronal signal transmission (see the text for details): Damage to peripheral organs initiates immune processes at the periphery, recruiting antigen-presenting cells (APCs) at the inflammatory site (1). These APCs migrate into lymphoid organs, where the transition to an adaptive immune response takes place (2). As a consequence, the clonal expansion of T-cells leads to the priming of B cells to produce antibodies (3,4). These antibodies diffuse into the central nervous system (CNS) through the blood brain barrier (BBB), or the circumventricular organs and other structures devoid of BBB (5). In the CNS, these antibodies target specific antigens and disrupt their function, causing neuronal death (6). Neuronal loss activates microglial cells that act as immune mediators in the CNS (7). The activated microglial cells phagocytose the proteins of dead neurons and present this neuronal fingerprint at their surface (8). Simultaneously, they produce pro-inflammatory cytokines and toxic molecules that compromise neuron survival (9). Eventually, in conjunction with the secretion of cytokines, microglia disturb astroglial functions, levels of vascular endothelial growth factor and intercellular adhesion molecule 1 (10), increasing the permeability of the BBB and favoring T-cell infiltration (11). T-cells have a synergistic effect on selective neuronal death by targeting neuronal antigens and priming microglia to consolidate the acquired immune response in the CNS (12,13). Alternatively, damage or pathogens within the CNS can initiate a noxious chronic innate immune response without components of systemic adaptive immunity (black arrows) (14) that can eventually promote infiltration through BBB leakage, resulting in an acquired immune response. MHC, major histocompatibility complex. Reproduced from[21] with permission from nature publishing group

Figure 2

(a) In healthy subjects, the primary motor area of the brain sends movement commands to the muscles via the spinal cord. (b) In many paralyzed people this pathway is interrupted, mostly due to a spinal cord injury. (c) In brain machine interface approach, electrodes measure activity from the brain. A computer based decoder translates this activity into commands for the control of muscles or prosthesis or a computer. The person visualizes the performance of the prosthesis and gives its feedback to the brain of the self. Reproduced from[36] with permission from laboratory of Albert-Ludwigs-University Freiburg, Germany. Available from: http://www.bmi.uni-freiburg.de

Figure 3

Experimental design used to test a closed-loop control brain-machine interface for motor control in macaque monkeys: Chronically implanted microwire arrays are used to sample the extracellular activity of populations of neurons in several cortical motor regions. Linear and nonlinear real time models are used to extract various motor-control signals from the raw brain activity. The outputs of these models are used to control the movements of a robotic arm. For instance, while one model might provide a velocity signal to move the robotic arm, another model, running in parallel, might extract a force signal that can be used to allow a robot gripper to hold an object during an arm movement. Artificial visual and tactile feedback signals are used to inform the animal about the performance of a robot arm controlled by brain-derived signals. Visual feedback is provided by using a moving cursor on a video screen to inform the animal about the position of the robot arm in space. Artificial tactile and proprioceptive feedback is delivered by a series of small vibromechanical elements attached to the animal's arm. This haptic display is used to inform the animal about the performance of the robot arm gripper (whether the gripper has encountered an object in space, or whether the gripper is applying enough force to hold a particular object). ANN, artificial neural network; LAN, local area network. Reproduced from[16] with permission from nature publishing group

Figure 4

Embodied control setup: Each monkey had its arms restrained (inserted up to the elbow in horizontal tubes, shown at bottom of image) and a prosthetic arm positioned next to its shoulder. Spiking activity was processed (boxes at top right) and used to control the three-dimensional arm velocity and the gripper aperture velocity in real time. Food targets were presented (top left) at arbitrary positions. Reproduced from[56] with permission from nature publishing group