Shunting for Alzheimer's disease: stymied by a different sort of placebo effect?

Many patients with spinal cord injury, stroke, or neurodegenerative diseases remain cognitively intact but are unable to communicate, move, or interact with the outside world. As a result, these injuries are devastating for the health and quality of life of patients and their families. In addition, the health care cost to society for the care of this population of patients is hundreds of millions of dollars (3, 13) and rises every year. There clearly is an incentive for clinicians and researchers in many fields to develop technologies to help patients with these kinds of brain, spinal cord, or neuromuscular damage to regain independence and quality of life, and the field of brain-computer interface (BCI) strives to use the patient’s own neural activity to achieve these ends (9). BCIs, otherwise known as brain-machine interfaces, record neural activity from the patient’s intact cortex (primary motor, premotor, or posteroparietal), use software algorithms to translate neural recordings into a usable output to estimate hand trajectory or cursor motion, and drive the control of a computer or robotic device. The most recent notable advance in the field of BCI, reported by Velliste et al. (18) from the University of Pittsburgh, gives us an encouraging glimpse of the potential BCI technology may have for these patients. Using a multielectrode array the size of a baby aspirin implanted in the primary cortex of a macaque monkey, the researchers trained the animal to manipulate a simple articulated arm with a pincer “hand” (the monkey’s own arms were gently restrained at its sides while the animal was sitting in a chair). After undergoing operant training for a grasping task, the monkey was able to use thoughts alone to reach out with the prosthetic arm, grasp a food treat with the pincer, and bring it to its mouth. The monkey’s behavior reinforced previous findings that when a primate learns to use a prosthesis, it becomes incorporated into its own internal body image (11): when a marshmallow stuck to the monkey’s lips, the animal used the prosthetic pincers as fingertips to nudge the treat into his awaiting mouth; the monkey licked treats off the arm as if it were licking food from its own fingers; and the animal avoided simple obstacles and grasped moving targets with little difficulty. The ease with which the monkey adapted to the prosthetic arm as a surrogate for its own bodes well for patients for whom this technology may be available in the future. This study comes from a laboratory that has contributed a tremendous amount to the understanding of the neurophysiological relationship between the cerebral cortex and action. However, although the work described in the article is undoubtedly an elegant demonstration of the practical application of BCI, it does not offer groundbreaking conceptual advances in the field. The technologies and algorithms described by Velliste et al. have already been demonstrated in human patients (5, 6, 15) and in monkeys (1, 2, 4, 12, 16, 17, 19). As the authors used the neural information to drive a motor prosthesis, they simply demonstrated a proof of principle of the practical application of BCI. However, these critiques should not detract from the significant impact of the article: what Velliste et al. demonstrated is an incremental advance in our knowledge of the capabilities of BCI neuroprostheses with today’s technology. Although the excitement and momentum within the field of BCI is growing, this is not the kind of technology that will be ready for widespread availability until a number of fundamental challenges are met. The motion of BCI-driven prostheses remains very crude because of the limited number of degrees of freedom interpreted by BCI algorithms (thus far). Significant increases in the degrees of freedom regarding control of the upper arm will be the next step in realizing the practical application of BCIdriven neuroprostheses. The reliability and longevity of implantable BCIs (electrocorticography and multielectrode arrays) remain subjects of heated debate, and noninvasive electroencephalographic BCIs require the wearer to have assistance to don cumbersome electrode caps (and their signal quality is disappointing). In addition, BCIs will remain confined to the laboratory environment until the imposing collection of bulky cables, amplifiers, computers, and robotic accouterments become miniaturized, fully implantable, and wireless. Once BCIs reliably meet these challenges, how will human patients actually benefit from neuromotor prostheses? There are 3 options. The first is functional electrical stimulation, a technique using electrical currents to activate nerves innervating extremities to integrate the patient’s own neuromuscular system into neuromotor prosthesis (7, 8, 14). The second option, assistive technology, promotes greater independence for people with disabilities by enabling them to perform tasks that they were formerly unable to accomplish or had great difficulty accomplishing, by providing enhancements to or changed methods of interacting with the technology needed to accomplish such tasks. The tablemounted DLR lightweight robotic arms, specially designed to perform dexterous hand actions (www.dlr.de), are examples of purpose-built assistive technology devices. The third option is a limb prosthesis for individuals who have had an amputation because of a limb injury, for example, a soldier injured by an improvised explosive device. An example is the Defense Advanced Research Projects Agency-funded DEKA prosthesis, an arm and hand prosthesis that performs and appears like a natural limb. Tactile feedback remains elusive, and haptics linked with cortical feedback is currently undergoing investigation (10). All neuromotor prosthesis technology advances aside, for people with locked-in syndrome, the ability to have even modest control of a computer for communication would be extremely helpful. The cardiac pacemaker and cochlear implant are examples of currently ubiquitous human-computer interfaces. The first cardiac pacemaker was the size of a file cabinet and was thought to be quackery by