Collaborative approach in the development of high-performance brain-computer interfaces for a neuroprosthetic arm: translation from animal models to human control.

Our research group recently demonstrated that a person with tetraplegia could use a brain-computer interface (BCI) to control a sophisticated anthropomorphic robotic arm with skill and speed approaching that of an able-bodied person. This multiyear study exemplifies important principles in translating research from foundational theory and animal experiments into a clinical study. We present a roadmap that may serve as an example for other areas of clinical device research as well as an update on study results. Prior to conducting a multiyear clinical trial, years of animal research preceded BCI testing in an epilepsy monitoring unit, and then in a short-term (28 days) clinical investigation. Scientists and engineers developed the necessary robotic and surgical hardware, software environment, data analysis techniques, and training paradigms. Coordination among researchers, funding institutes, and regulatory bodies ensured that the study would provide valuable scientific information in a safe environment for the study participant. Finally, clinicians from neurosurgery, anesthesiology, physiatry, psychology, and occupational therapy all worked in a multidisciplinary team along with the other researchers to conduct a multiyear BCI clinical study. This teamwork and coordination can be used as a model for others attempting to translate basic science into real-world clinical situations.

Deleterious impact of a γ-aminobutyric acid type A receptor preferring general anesthetic when used in the presence of persistent inflammation.

BACKGROUND: Experimental data suggest general anesthetics preferring γ-aminobutyric acid receptor type A may increase postoperative pain in patients with persistent inflammation. The current study was designed to begin to test this hypothesis. METHODS: Groups of rats were defined by the presence of inflammation, surgical intervention, and/or the type of general anesthetic used for a 3-h period of anesthesia. Persistent inflammation was induced with complete Freund adjuvant. The surgical intervention was a plantar incision. Three mechanistically distinct general anesthetics were used: pentobarbital, ketamine/xylazine, and isoflurane. Ongoing pain and hypersensitivity were assessed with guarding behavior analysis and the von Frey test, respectively. RESULTS: There was no influence of general anesthetic type on the magnitude or time course of recovery from postoperative hypersensitivity in the absence of persistent inflammation. However, in the presence of persistent inflammation, recovery from hypersensitivity was significantly slower in the pentobarbital group than in the ketamine/xylazine or isoflurane groups. The pentobarbital effect was significant within 3 days of surgery and persisted through the remainder of the testing period. A comparable delay in recovery was observed in pentobarbital-anesthetized inflamed rats not subjected to hind paw incision. The time to 50% recovery in the pentobarbital-treated inflamed groups was almost double that in the other groups. No differences were observed between ketamine/xylazine and isoflurane. Pentobarbital exposure did not increase guarding scores. CONCLUSIONS: These results suggest that general anesthetics preferring γ-aminobutyric acid receptor type A may have deleterious consequences when used in the presence of persistent inflammation.

Anesthetics and cerebral metabolism.

PURPOSE OF REVIEW: This review focuses on the utilization of the effects of general anesthetics on cerebral metabolism as revealed by imaging for therapeutic and preventive purposes, for understanding mechanisms of anesthetic action, and for elucidating mechanisms of cerebral processing in humans. RECENT FINDINGS: General anesthetics suppress cerebral metabolism significantly. This effect has been used for neuroprotection during inadequate cerebral blood flow. With the advent of noninvasive imaging techniques, this suppression has also been used to image and map the sites of anesthetic action in the living human brain. Volatile agents, intravenous anesthetics, and analgesics have all begun to be explored using mostly positron emission tomography. The ability of anesthetics to change global baseline brain metabolism has created the opportunity to examine the relevance of global baseline (resting) brain activity in terms of region-specific cerebral processing. SUMMARY: Anesthetics experimentally appear to be useful for neuroprotection, at least during the early post-ischemic period. Identification of the cerebral sites of anesthetic action by in vivo human brain imaging provides new insights into the mechanism of action of these agents. Anesthetic-related manipulation of baseline brain metabolism demonstrates the significant contribution of this global activity to regional cerebral processing.

Early decay of pain-related cerebral activation in functional magnetic resonance imaging: comparison with visual and motor tasks.

BACKGROUND: Although pain-related activation was localized in multiple brain areas by functional imaging, the temporal profile of its signal has been poorly understood. The authors characterized the temporal evolution of such activation in comparison to that by conventional visual and motor tasks using functional magnetic resonance imaging. METHODS: Five right-handed volunteers underwent whole brain echo-planar imaging on a 3 T magnetic resonance imaging scanner while they received pain stimulus on the right and left forearm and performed visually guided saccade and finger tapping tasks. Pain stimulus on the right and left forearm consisted of four cycles of 15-s stimulus at 47.2-49.0 degrees C, interleaved with 30-s control at 32 degrees C, delivered by a Peltier-type thermode, and visually guided saccade and finger tapping of three cycles of 30-s active and 30-s rest conditions. Voxel-wise t statistical maps were standardized and averaged across subjects. Blood oxygenation level-dependent signal time courses were analyzed at local maxima of representative activation clusters (t > 3.5). RESULTS: Pain stimulus on the right forearm activated the secondary somatosensory (S2), superior temporal, anterior cingulate, insular, prefrontal cortices, premotor area, and lenticular nucleus. Pain stimulus on the left forearm activated similar but fewer areas at less signal intensity. The S2 activation was dominant on the contralateral hemisphere. Pain-related activation was statistically weaker and showed less consistent signal time courses than visually guided saccade- and finger tapping-related activation. Pain-related signals decayed earlier before the end of stimulus, in contrast to well-sustained signal plateaus induced by visually guided saccade and finger tapping. CONCLUSIONS: The authors speculate that pain-related blood oxygenation level-dependent signals were attenuated by the pain-induced global cerebral blood flow decrease or activation of the descending pain inhibitory systems.