The authors note, "For the 'hybrid' location discrimination task, we report data obtained from 27 electrodes, 16 of which were in area 1; the 11 electrodes in area 3b were divided evenly across the two animals (6 and 5). We had previously tested all of the electrodes, including those in area 3b, in the detection and discrimination tasks (as shown in Fig. 3) and found them all to yield approximately equivalent performance (see Fig 3A). We noticed in the hybrid location discrimination task, however, that one of the animals performed much more poorly based on stimulation of area 3b than it did based on stimulation of area 1 (while the other animal performed better based on stimulation of area 1). Having no reason to question any of the arrays, we attributed this discrepancy to differences across animals and arrived at the conclusion, based on pooled data from both animals, that stimulation of the two areas yields equivalent performance in the 'hybrid location discrimination' task. The overall conclusion, then, was that stimulation of neurons in area 3b and 1 evokes percepts that are equally localized on the skin."Shortly after publication of the paper, we repeated detection experiments across the arrays and found that the animal could no longer detect stimulation through the array in area 3b that had yielded poor performance in the hybrid location discrimination task. It is therefore likely that this array had failed between the time we conducted the initial detection and discrimination experiments and the time we conducted the hybrid location discrimination task (which required 2-3 months of retraining). If this is the case, and we eliminate data from that bad array, then the median performance on hybrid trials is 83% (up from the 80% that was originally reported), which is still statistically poorer than that on the location-matched mechanical trials [median difference between performance on mechanical and hybrid trials was 3.3% rather than 5.6%, t (119) = 6.1, P < 0.001] (see the corrected Fig. 2). Thus, we probably underestimated overall performance on hybrid trials, and thus the degree to which artificial percepts are localized, in the original publication. Importantly, however, performance on hybrid trials based on stimulation of area 3b was significantly better than performance based on stimulation of area 1 [median Δp = 0.028 and 0.054 for areas 3b and 1, respectively; t test: t (76) = 2.8, P < 0.01]. Thus, based on the data obtained from only one animal, it seems as though stimulation of area 3b elicits more localized percepts than does stimulation of area 1, as might be expected given that neurons in area 3b tend to have smaller receptive fields than their counterparts in area 1 (1, 2)."As a result of this error, Fig. 2 and its legend appeared incorrectly. The corrected figure and its corresponding legend appear below. On both mechanical and hybrid trials, the relative locations of stimuli applied to widely spaced digits were more accurately discriminated than were the relative locations of stimuli applie...

We report on our efforts to establish an animal model for the development and testing of a cortical visual prostheses. One-hundred-fifty-two electrodes were implanted in the primary visual cortex of a rhesus monkey. The electrodes were made from iridium with an activated iridium oxide film, which has a large charge capacity for a given surface area, and insulated with parylene-C. One-hundred-fourteen electrodes were functional after implantation. The activity of small (2-3) neuronal clusters was first recorded to map the visually responsive region corresponding to each electrode. The animal was then trained in a memory (delayed) saccade task, first with a visual target, then to a target defined by direct cortical stimulation with coordinates specified by the stimulating electrode's mapped receptive field. The SD of saccade endpoints was approximately 2.5 larger for electrically stimulated versus visual saccades; nevertheless, when trial-to-trial scatter was averaged out, the correlation between saccade end points and receptive field locations was highly significant and approached unity after several months of training. Five electrodes were left unused until the monkey was fully trained; when these were introduced, the receptive field-saccade correlations were high on the first day of use (R = 0.85, P = 0.03 for angle, R = 0.98, P < 0.001 for eccentricity), indicating that the monkey had not learned to perform the task empirically by memorizing reward zones. The results of this experiment suggest the potential for rigorous behavioral testing of cortical visual prostheses in the macaque.

In the field of visual prosthesis research, it has generally been held that animal models are limited to testing the safety of implantable hardware due to the inability of the animal to provide a linguistic report of perceptions. In contrast, vision scientists make extensive use of trained animal models to investigate the links between visual stimuli, neural activities, and perception. We describe an animal model for cortical visual prosthesis research in which novel animal psychophysical testing has been employed to compensate for the lack of a linguistic report. One hundred and fifty-two intracortical microelectrodes were chronically implanted in area V1 of a male macaque. Receptive field mapping was combined with eye-tracking to develop a reward-based training procedure. The animal was trained to use electrically induced point-flash percepts, called phosphenes, in performing a memory saccade task. It is our long-term goal to use this animal model to investigate stimulation strategies in developing a multichannel sensory cortical interface.

Tactile sensation is critical for effective object manipulation, but current prosthetic upper limbs make no provision for delivering somesthetic feedback to the user. For individuals who require use of prosthetic limbs, this lack of feedback transforms a mundane task into one that requires extreme concentration and effort. Although vibrotactile motors and sensory substitution devices can be used to convey gross sensations, a direct neural interface is required to provide detailed and intuitive sensory feedback. In light of this, we describe the implementation of a somatosensory prosthesis with which we elicit, through intracortical microstimulation (ICMS), percepts whose magnitude is graded according to the force exerted on the prosthetic finger. Specifically, the prosthesis consists of a sensorized finger, the force output of which is converted into a regime of ICMS delivered to primary somatosensory cortex through chronically implanted multi-electrode arrays. We show that the performance of animals (Rhesus macaques) on a tactile task is equivalent whether stimuli are delivered to the native finger or to the prosthetic finger.

When an odorant is presented to one side of the nose and air to the other, the ability to localize which side received the odorant depends upon trigeminal nerve stimulation. It has been shown that performance on this lateralization task increases as stimulus concentration increases. In this study, we determined the influences of stimulus volume and sex on the ability to localize each of 8 odorants presented at neat concentrations: anethole, geraniol, limonene, linalool, menthol, methyl salicylate, phenyl ethanol, and vanillin. At a low stimulus volume (11 mL), only menthol was localized at an above-chance level. At a high stimulus volume (21 mL), above-chance localization occurred for all odorants except vanillin. Women were significantly better than men in localizing menthol. Stimuli rated as most intense were those that were most readily localized. The detection performance measures, as well as rated intensity values, significantly correlated with earlier findings of the trigeminal detectability of odorants presented to anosmic and normosmic subjects. This study suggests that differences in stimulus volume may explain some discrepant findings within the trigeminal chemosensory literature and supports the concept that vanillin may be a "relatively pure" olfactory stimulus.

The purpose of this study was to identify the nephron and cell sites involved in the renal metabolism of alpha-rat atrial natriuretic peptide (alpha-rANP) and to examine the degradation products of the peptide. In micro-dissected nephrons 125I-labeled ANP degradation rate was highest in proximal convoluted (PCT) and straight tubules and lowest in glomeruli and papillary collecting tubules, indicating that the sites of ANP degradation and of the receptors that mediate its biological activity in the nephron do not coincide. Among subcellular fractions of cortical homogenates, the luminal membranes were the most active in metabolizing ANP. In contrast, ANP degradation by isolated basolateral membranes was negligible, and the basolateral uptake route in intact tubules did not contribute significantly to its catabolism. Cortical homogenates, luminal membranes, and isolated PCT degraded ANP without evidence of saturation up to pharmacological concentrations (10(-6) M) of the peptide. A major intermediate metabolite was rapidly formed by luminal membranes and was identified with use of a sequence and compositional analysis. This metabolite had the same amino acid sequence as ANP with a cleavage at position Cys7-Phe8, and the disulfide bridge was preserved. These results demonstrate a rapid degradation of ANP by kidney tissue and suggest that the luminal membrane of the proximal tubule is a major nephron site of ANP catabolism.

No abstract

Glossopharyngeal neuralgia (GN) triggered by non-noxious stimuli at multiple cephalic and extracephalic sites with positron emission tomography (PET) evidence for involvement of the upper brainstem has never been reported. We present such a patient, a 73-year-old man who since the age of 50 had suffered from GN with a high recurrence rate and very severe unilateral, non-familial GN episodes with very easy trigger zones widely extending beyond the n IX territory. Extensive neuroimaging and neurophysiological tests detected no precise underlying cause. PET scan revealed activation in the upper brainstem on extracephalic triggers. Single-fibre electromyography data will be discussed. We hypothesize that deficient inhibition as seen in trigeminal nociceptive reflexes on the level of brainstem interneurons, a functional lesion in the primary somatosensory cortex-sensory thalamic nuclei circuit and the dorsal column-thalamic pathway both activated by light touch may in part be involved in the extracephalic triggering.