On Oct. 16, 2008, Julie Steenhuysen filed a report for Reuters entitled "Device helps monkeys move paralyzed wrists" describing a recent break through in fundamental research on brain-machine interfaces that considerably broadens avenues for the prosthetic control of limb movement. The findings are published in the journal Nature (Moritz and others, 2008). National Public Radio's Morning Edition provided an interview by Dan Charles entitled "Monkey Studies Could Help Paralyzed Humans" with the first author of the study. I have written about such interfaces in my post dated Jan 23, 2008.
The researchers at the University of Washington temporarily numbed nerves controlling arm movement in monkeys. Fine electrical leads were implanted into the area of cerebral cortex that controls limb movement known as motor cortex. The leads were used to record the electrical signals that nerve cells use to control skeletal muscle contraction. The signals were amplified, electronically transformed and fed into wire electrodes implanted into the muscles of the numbed arm. The monkeys learned to execute goal-directed movements with this limb. The results constitute a mile stone proving both the applicability of the electronic interface and the versatility of the motor system to utilize the new extraordinary tool in a meaningful fashion.
The nerve cells in our central nervous system that innervate the skeletal musculature are known as motor neurons. When peripheral nerve injury severs their axons, that is the nerve fibers that establish the connections with the muscle fibers, motor neurons can regenerate the disrupted connections. During this period, the cells are subjected to remarkable alterations. A glial reaction ensues in their vicinity. In my own experience, strong signs of the glial response can be detected on histological tissue sections within four days after nerve injury. The signs are visible on this micrograph from a transverse section through the brain stem of a rat.
|microglia, courtesy of J.A. McKanna|
The hypoglossal nerve, that is the twelfth cranial nerve innervating the muscles of the tongue, was damaged on the right side (left in the micrograph). The bodies of nerve cells are stained blue in the micrograph. Microglia are stained black. The cell bodies of the axotomized motor neurons (asterisk) are located left of the center of the section in an area called hypoglossal nucleus. Microglia (arrowhead) are gathered in great number among the axotomized motor neurons and wrap themselves around their bodies (arrow), detaching incoming nerve contacts known as synapses that convey command and control for muscle contraction from the fore brain. The motor neurons undergo chromatolysis and increase protein synthesis. David Bodian described the cellular changes using electron microscopy in great detail in the Johns Hopkins Hospital Bulletin (Bodian, 1964). Blinzinger and Kreutzberg (1968) were the first to identify the cells that insert themselves between the motor neuron and the synapses as microglia. After roughly two months the glial reaction ceases, the synapses re-attach to the cell bodies, and the motor neurons regain much of their original appearance. Major histo-compatibility complexes have been identified as one major group of signal molecules that control the observed glial and motor neuron responses to axotomy (Oliveira and others, 2004).
The ability of motor neurons to re-establish disrupted muscle innervation is a fascinating example of our brain's ability to recover from injury. However, it is important to note that the repair is imperfect. The novel innervation commonly remains below original strength and the endings of the motor neurons may not succeed in finding their original muscle fibers (Madaschi and others, 2003). Intriguingly, the nerve cells in the central nervous system are able to adjust to the altered peripheral innervation. Sprouting of novel connections has been proposed as mechanism (Fujito and Aoki, 2002). In fact, the plasticity of the motor system is so great that animals reportedly learn meaningful limb movements even after the surgical cross of nerves controlling antagonistic muscles [Sperry, 1941 (reviewed by Todman, 2008)].
Taking this enormous flexibility of the motor system into consideration, the directed arm movements of the interfaced monkeys Moritz and others (2008) observed may not entirely come as a surprise. Doubtlessly, the technology to transform the nerve cell signals recorded in the cerebral motor cortex into meaningful stimuli for the arm muscles is a daunting achievement. However, it is important to emphasize that the success of this method ultimately relies upon the nerve cells that alter their electrical discharges in order to produce the desired movement. As pointed out on the National Public Radio broadcast, the fascinating discovery is the rapidity with which the nerve cells learn to direct a movement under extraordinary experimental conditions. The question remains to be answered whether special cells or a special ensemble of cells is needed to produce fine-grain limb control.
- On Feb. 10, 2009, Pam Belluck reported in her post entitled "In New Procedure, Artificial Arm Listens to Brain" for The New York Times on a promising variation of this idea published in The Journal of the American Medical Association (JAMA 301(6):619-628). With the new procedure, Kuiken and others (2009) planted wire electrodes over functional muscle groups that a patient with a lost limb can control. The electrical nerve signals recorded from the electrodes when the patient is using the underlying muscles are subsequently employed to steer a prosthesis replacing the missing limb. With practice, the patients learn to substitute the contractions of the intact muscles with prosthetic limb movements to the extent that they feel the limb manipulated when the skin over the muscles is touched (02/11/2009).
- Blinzinger K, Kreutzberg G (1968) Displacement of synaptic terminals from regenerating motoneurons by microglial cells. Cell Tissue Res 85: 145-157.
- Bodian D (1964) An electron-microscopic study of the monkey spinal cord. I. Fine structure of normal motor column. II. Effects of retrograde chromatolysis. III. Cytological effects of mild and virulent poliovirus infection. Bull Johns Hopkins Hosp 114: 13-119.
- Fujito Y, Aoki M (2002) Distal forelimb cross-innervation effectively induces formation of corticorubral synapses. Neuroreport 13: 2121-2124.
- Kuiken TA, Li G, Lock BA, Lipschutz RD, Miller LA, Stubblefield KA, Englehart KB (2009) Targeted muscle reinnervation for real-time myoelectric control of multifunction artificial arms. JAMA 301: 619-628.
- Madaschi L, Di Giulio AM, Gorio A (2003) Muscle Reinnervation and IGF-I Synthesis Are Affected by Exposure to Heparin: An Effect Partially Antagonized by Anti-Growth Hormone-Releasing Hormone. Neurochem Res 28: 163-168.
- Moritz CT, Perlmutter SI, Fetz, EE (2008) Direct control of paralysed muscles by cortical neurons. Nature 456: 639-642.
- Oliveira AL, Thams S, Lidman O, Piehl F, Hökfelt T, Kärre K, Lindå H, Cullheim S (2008) A role for MHC class I molecules in synaptic plasticity and regeneration of neurons after axotomy. Proc Natl Acad Sci U S A 101: 17843-17848.
- Sperry RW (1941) The effect of crossing antagonistic muscles in the hind limb of the rat. J Comp Neurol, 75: 1-19.
- Todman, D (2008) History of Neuroscience: Roger Sperry (1913-1994), IBRO History of Neuroscience