Neurobiology of Disease 83 (2015) 180–190 Contents lists available at ScienceDirect Neurobiology of Disease journal homepage: www.elsevier.com/locate/ynbdi Review Brain-controlled muscle stimulation for the restoration of motor function Christian Ethier a, Lee E. Miller a,b,c,⁎ a Department of Physiology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Ave., Chicago, IL 60611, USA b Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road Evanston, IL 60208, USA c Department of Physical Medicine and Rehabilitation, Feinberg School of Medicine, Northwestern University, 345 E. Superior Ave., Chicago, IL 60611,USA article info abstract Article history: Loss of the ability to move, as a consequence of spinal cord injury or neuromuscular disorder, has devastating Received 17 May 2014 consequences for the paralyzed individual, and great economic consequences for society. Functional electrical Revised 14 October 2014 stimulation (FES) offers one means to restore some mobility to these individuals, improving not only their auton- Accepted 20 October 2014 omy, but potentially their general health and well-being as well. FES uses electrical stimulation to cause the par- Available online 28 October 2014 alyzed muscles to contract. Existing clinical systems require the stimulation to be preprogrammed, with the patient typically using residual voluntary movement of another body part to trigger and control the patterned Keywords: Functional electrical stimulation stimulation. The rapid development of neural interfacing in the past decade offers the promise of dramatically Spinal cord injury improved control for these patients, potentially allowing continuous control of FES through signals recorded Paralysis from motor cortex, as the patient attempts to control the paralyzed body part. While application of Brain–machine interface these ‘brain–machine interfaces’ (BMIs) has undergone dramatic development for control of computer cursors Motor cortex and even robotic limbs, their use as an interface for FES has been much more limited. In this review, we consider both FES and BMI technologies and discuss the prospect for combining the two to provide important new options for paralyzed individuals. © 2014 Elsevier Inc. All rights reserved. Contents 1. Introduction.............................................................. 181 2. FESsystems.............................................................. 181 2.1. MuscleactivationbyFES..................................................... 181 2.2. FESforlowerlimbfunction.................................................... 182 2.3. FESforupperlimbfunction.................................................... 183 3. Decodingmotorintentfromthebrain................................................... 183 3.1. ScalpEEGasabraininterface................................................... 183 3.2. Fieldrecordingusingelectrodegridsimplantedonthesurfaceofthebrain............................... 184 3.3. Intracorticalrecordingofneuronalactionpotentials......................................... 184 4. Approachestobrain-controlledFES.................................................... 184 5. Brain-controlledmusclestimulationforthereplacementoffunction...................................... 185 5.1. Restorationofgrasping...................................................... 185 5.2. Restorationoflowerlimbfunction................................................. 186 5.3. Remainingchallengesforbrain-controlledFES............................................ 186 6. Conclusions............................................................... 187 Acknowledgments.............................................................. 187 References.................................................................. 187 ⁎ Corresponding author at: Department of Physiology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Ave., Chicago, IL 60611, USA. Fax: +1 312 503 5101. E-mail address: [email protected] (L.E. Miller). Available online on ScienceDirect (www.sciencedirect.com). http://dx.doi.org/10.1016/j.nbd.2014.10.014 0969-9961/© 2014 Elsevier Inc. All rights reserved. C. Ethier, L.E. Miller / Neurobiology of Disease 83 (2015) 180–190 181 1. Introduction cord injury, stroke, multiple sclerosis, or cerebral palsy. In addition to the replacement of motor function that is its most obvious benefit, FES Paralysis resulting from spinal cord injury (SCI), cortical lesion or neuro- can have more general benefit as well. FES improves the contractile muscular disease is devastating, dramatically reducing the range of activi- force of the remaining motor units to which the patient has voluntary ties of daily living (ADL) and quality of life of patients. In addition to the access (Baldi et al., 1998; Powell et al., 1999), as would traditional direct effects, a number of secondary complications emerge as a result of muscular training. It also may improve the range of motion of the affect- disuse, such as muscle atrophy, contractures and pressure sores (Baldi ed limb beyond that of passive physical therapy (Kraft et al., 1992; et al., 1998; Ragnarsson, 2008). Among those patients with tetraplegia, Pandyan et al., 1997), particularly for less severely affected patients the great majority identify the return of hand function as their most critical (Powell et al., 1999; Sonde et al., 1998; von Lewinski et al., 2009). FES need (Anderson, 2004; French et al., 2010). Those patients with loss only of may also reduce spasticity and contractures, though this remains un- lower limb function list a number of different priorities. If the motoneurons clear (Alfieri, 2001; Malhotra et al., 2012). In addition, there are indirect remain intact after injury, muscles can still be made to contract through the effects that result from contracting paralyzed muscles: activation of the application of electric currents to the nerve or neuromuscular junction, a cardiopulmonary system, strengthening of bones, and relief of pressure procedure referred to as functionalelectricalstimulation(FES)(Peckham sores. Finally, the neuronal activity generated by FES may lead to and Knutson, 2005; Ragnarsson, 2008). In the past several decades, impor- activity-dependent plastic changes in the nervous system. These effects tant progress has been made using FES to assist or restore motor function in can be difficult to evaluate in light of the changes in the periphery. How- patients, enabling them to improve their gait (Daly et al., 2011; Granat et al., ever, FES has been shown to contribute to neurogenesis (Liuetal., 1993; Thrasher et al., 2005), grasp objects (Alon and McBride, 2003; 2013a), axonal growth (Al-Majed et al., 2004; Liu et al., 2013b), sensory Peckham et al., 1980, 2001; Popovic et al., 2002), and to augment bowel neuron regeneration (Geremia et al., 2007), and to promote recovery of and bladder function (Gaunt and Prochazka, 2006). FES systems can be of spinal reflexes (Knikou and Conway, 2005; Lynskey et al., 2008). great benefit to paralyzed patients, by providing an increase in autonomy Popovic et al. listed three requirements that need to be fulfilled in through improvements in their activities of daily living. order to include FES as a rehabilitation tool (Popovic et al., 2001). A variety of control sources have been used to command FES. Foot First, the muscles that are intended for FES need to be accessible for drop correction can be controlled by a simple switch activated by electrode placement. Surface electrodes have few contraindications sensors near the heel of the foot, by sensing acceleration or by signals aside from the pain they may cause if sensation is intact, but they cannot recorded from the peroneal nerve (Pappas et al., 2001; Popovic et al., activate deeper muscles well. Percutaneous or implanted electrodes are 1993; Rueterbories et al., 2010; Skelly and Chizeck, 2001; Tong and more selective, but are more invasive and may not be indicated for some Granat, 1999; Williamson and Andrews, 2000). Likewise, switches can patients, particularly in the early stages after injury. be used to activate pre-programmed stimulation patterns for grasp, Second, there should not be a major degree of motoneuron or nerve and to initiate sit-to-stand movements (Gallien et al., 1995; Graupe root damage of the stimulated muscle. Intramuscular stimulation et al., 1998; Graupe and Kohn, 1998). More finely-graded control can normally activates muscles indirectly, by first evoking action potentials be achieved by joint angle sensors or measurement of residual muscle in the nerve terminals. SCI patients often have some level of motoneuro- activity. However, these control modes are limited in bandwidth, and nal damage around the level of injury, which may restrict the use of FES are initially unnatural and unintuitive for patients. Furthermore, with for some muscles. Activation of denervated muscles is possible with increasingly high level SCI, the patients have at once greater need for much higher current, but is not very effective as a means to recruit replaced function and fewer available control options. muscles in a selective and functionally useful manner (Kern et al., The advances made in the field of brain–machine interfaces over the 2002; Mayr et al., 2002). past 10 years provide the possibility to extract a user's own movement Third, Popovic et al. noted that for FES to be useful, the voluntary intent directly from the brain. The majority of these applications function of the more proximal limb muscles must