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(PSYCHIATRIC TIMES) - Practical Application of BCIs Near
Mind-controlled artificial limbs were once the stuff of sci-fi and then were regarded as a concept that would not see clinical application until a far distant future. However, clinical application may be only a few years away, in light of prolific work and significant progress in the development of brain-computer interfaces (BCIs). BCIs are devices that record neuronal activity generated from voluntary motor intentions. A number of researchers, including Mandayam Srinivasan, PhD, director of The Touch Lab at Massachusetts Institute of Technology; Andrew Schwartz, PhD, professor of neurobiology at the University of Pittsburgh School of Medicine; and Jose M. Carmena, PhD, postdoctoral fellow in neurobiology at Duke University, have had success working with monkeys in developing robotic arms, and now studies in humans are under way. Most current applications of this research rely on use of electrodes that are either (1) implanted within the cortex of the subject, (2) implanted less invasively at sites on the surface of the brain (electrocorticography [ECoG]), or (3) are noninvasively placed against the head (ie, electroencephalography [EEG]). The second of these approaches, ECoG, developed by Gerwin Schalk, MS, a research scientist at the Wadsworth Center of the New York State Department of Health, attempts to resolve the pitfalls inherent in the other 2 modalities. Cortical implantation can result in infection. In addition, eventual scarring around the implant can compromise efficiency of data collection required for BCI functionality. On the other hand, measuring brain waves with EEG results in a less precise interface and more labor for the participant, who must learn how to use the interface. Using the ECoG recording method, Schalk and his team and a team from Washington University in St Louis worked with a patient with epilepsy who through use of the ECoG-type BCI was able to move a cursor on a computer screen with his mind. In addition, a team led by Nils Danielsen, MD, PhD, associate professor in the Department of Physiological Sciences at Lund University, Sweden, is developing a prosthetic hand utilizing electromyography (EMG) and a “data glove” that collects information from a person and trains the computerized control system. In time, use of the data glove is discontinued so that the person can manipulate a virtual hand through EMG signals and interpretive data stored in the control system. The technology ultimately will be applied to creation of next-generation limb prostheses. Key to creating an efficient and naturalistic device is refining technology to measure and interpret not single target neurons, but the elaborate complex of neuronal activity that occurs with voluntary motor intention. One team developing such technology is led by Richard Andersen, PhD, Boswell Professor of Neuroscience at the California Institute of Technology. The technology, which involves implantation of an electrode into the parietal cortex, collects “local field potentials”— activity from hundreds of thousands of brain cells. In working with a trained macaque monkey, researchers were able to record activity related to both intention to move and actual voluntary movements. The data were used to train the interface. Again, the end result of that particular experiment was that the monkey was able to move a cursor on a computer screen with its mind. ■
Promising Future Uses for Currently Available Agents
Promising findings from recently reported trial results suggest that certain currently available agents have a potential for expanded indications in clinical neurology. Donepezil, an acetylcholinesterase inhibitor widely used to ameliorate memory loss in patients with Alzheimer disease (AD), may also improve cognitive function in patients with multiple sclerosis (MS). Although treatment of MS generally focuses on managing physical manifestations of disease, an estimated 50% of patients will experience some degree of cognitive impairment. A 24-week, placebo-controlled study of donepezil in 69 patients with MS, led by Lauren Krupp, MD, director of neuropsychology research at Stony Brook University Hospital in Stony Brook, NY, found that 54% of 35 patients who received the study drug showed improvement on the Selective Reminding Test, compared with 29% of 34 patients who received placebo. In addition, when patients were asked if they felt that their memory had improved, 66% of those who received the study drug reported improvement, compared with 32% of patients who received placebo. The promising results of this small study warrant further, larger clinical trials. For more information, see Krupp LB, Christodoulou C, Melville P, et al. Donezepil improved memory in multiple sclerosis in a randomized clinical trial. Neurology. 2004; 63:1579-1585. Findings from a study led by Takashi Ohrui, MD, of the Department of Geriatric and Respiratory Medicine at Tohoku University School of Medicine in Sendai, Japan, suggest that angiotensin-converting enzyme (ACE) inhibitors that penetrate the blood-brain barrier may have therapeutic value in the treatment of AD. The study, which involved 162 patients with mild to moderate AD and high blood pressure randomized to receive either a brainpenetrating ACE inhibitor (perindropril or captopril), a non–brain-penetrating ACE inhibitor (enalapril or imidapril), or a calcium channel blocker (nifedipine or nilvadipine), examined and compared thinking and memory skills at baseline and at 1 year. The average Mini-Mental State Examination score at baseline was 20. At 1 year, scores for patients receiving a brain-penetrating ACE inhibitor declined by an average of 0.6 points. Scores for those receiving a non–brain-penetrating ACE inhibitor declined by 4.6 points, and for those receiving calcium channel blockers, scores declined by 4.9 points. The researchers comment that brain-penetrating ACE inhibitors appear to have the ability to slow the rate of cognitive decline in mild to moderate AD. Although researchers do not know the mechanism of action, Dr Ohrui and colleagues suspect that it is related to regulation of the renin-angiotensin system within the brain, noting that ACE is overexpressed in the hippocampus, frontal cortex, and caudate nucleus of persons with AD. However, David Knopman, MD, professor of neurology at the Mayo Medical School in Rochester, NY, and Steven DeKosky, MD, director of the Alzheimer’s Disease Research Center at the University of Pittsburgh, note that the findings should be viewed with caution. Although patients were randomized to 3 different therapeutic protocols, the medications were not administered in a blinded fashion—a circumstance that risks introducing a bias into the study results. The rates of cognitive decline, particularly those seen among patients receiving the non–brain-penetrating ACE inhibitors and calcium channel blockers, were markedly higher than those seen in similar, previous studies, raising doubts about the accuracy of the findings. In addition, the study did not determine whether a difference in effect was achieved between the brain-penetrating ACE inhibitors alone. In response, Dr Ohrui said he was wholly in agreement with comments made by his peers. “We need a large, randomized, double- blinded, prospective study to confirm our results,” he said in correspondence with Applied Neurology, but he noted that his team did not have immediate plans to conduct such a study. For more information, see Ohrui T, Tomita N, Sato-Nakagawa T. Effects of brain-penetrating ACE inhibitors on Alzheimer disease progression. Neurology. 2004;63:1324-1325.

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