PubMed Health⌕ Search

Biomedical subjects

D C Bradley

Publications and source records attributed to D C Bradley.

At least 19 recordsLinked to original sources
PubMed2004

Visuotopic mapping through a multichannel stimulating implant in primate V1.

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.

Animals↗
PubMed1999

The contributions of vestibular signals to the representations of space in the posterior parietal cortex.

Vestibular signals play an important role in spatial orientation, perception of object location, and control of self-motion. Prior physiological research on vestibular information processing has focused on brainstem mechanisms; relatively little is known about the processing of vestibular information at the level of the cerebral cortex. Recent electrophysiological experiments examining the use of vestibular canal signals in two different perceptual tasks are described: computation of self motion and localization of visual stimuli in a world-centered reference frame. These two perceptual functions are mediated by different parts of the posterior parietal cortex, the former in the dorsal aspect of the medial superior temporal area (MSTd) and the latter in area 7a.

Animals↗
PubMed1999

Influence of gaze rotation on the visual response of primate MSTd neurons.

When we move forward, the visual image on our retina expands. Humans rely on the focus, or center, of this expansion to estimate their direction of heading and, as long as the eyes are still, the retinal focus corresponds to the heading. However, smooth rotation of the eyes adds nearly uniform visual motion to the expanding retinal image and causes a displacement of the retinal focus. In spite of this, humans accurately judge their heading during pursuit eye movements and during active, smooth head rotations even though the retinal focus no longer corresponds to the heading. Recent studies in macaque suggest that correction for pursuit may occur in the dorsal aspect of the medial superior temporal area (MSTd) because these neurons are tuned to the retinal position of the focus and they modify their tuning during pursuit to compensate partially for the focus shift. However, the question remains whether these neurons also shift focus tuning to compensate for smooth head rotations that commonly occur during gaze tracking. To investigate this question, we recorded from 80 MSTd neurons while monkeys tracked a visual target either by pursuing with their eyes or by vestibulo-ocular reflex cancellation (VORC; whole-body rotation with eyes fixed in head and head fixed on body). VORC is a passive, smooth head rotation condition that selectively activates the vestibular canals. We found that neurons shift their focus tuning in a similar way whether focus displacement is caused by pursuit or by VORC. Across the population, compensation averaged 88 and 77% during pursuit and VORC, respectively (tuning shift divided by the retinal focus to true heading difference). Moreover the degree of compensation during pursuit and VORC was correlated in individual cells (P < 0.001). Finally neurons that did not compensate appreciably tended to be gain-modulated during pursuit and VORC and may constitute an intermediate stage in the compensation process. These results indicate that many MSTd cells compensate for general gaze rotation, whether produced by eye-in-head or head-in-world rotation, and further implicate MSTd as a critical stage in the computation of heading. Interestingly vestibular cues present during VORC allow many cells to compensate even though humans do not accurately judge their heading in this condition. This suggests that MSTd may use vestibular information to create a compensated heading representation within at least a subpopulation of cells, which is accessed perceptually only when additional cues related to active head rotations are also present.

Action Potentials↗
PubMed1998

Center-surround antagonism based on disparity in primate area MT.

Most neurons in primate visual area MT have a large, modulatory region surrounding their classically defined receptive field, or center. The velocity tuning of this "surround" is generally antagonistic to the center, making it potentially useful for detecting image discontinuities on the basis of differential motion. Because classical MT receptive fields are also disparity-selective, one might expect to find disparity-based surround antagonism as well; this would provide additional information about image discontinuities. However, the effects of disparity in the MT surround have not been studied previously. We measured single-neuron responses to variable-disparity moving patterns in the MT surround while holding a central moving pattern at a fixed disparity. Of the 130 neurons tested, 84% exhibited a modulatory surround, and in 52% of these, responses were significantly affected by disparity in the surround. In most cases, disparity effects in the surround were antagonistic to the center; that is, neurons were generally suppressed when center and surround stimuli had the same disparity, with decreasing suppression as the center and surround stimuli became separated in depth. Also, the effects of disparity and direction were mainly additive; i.e., disparity effects were generally independent of direction, and vice versa. These results suggest that the MT center-surround apparatus provides information about image discontinuities, not only on the basis of velocity differences but on the basis of depth differences as well. This supports the hypothesis that MT surrounds have a role in image segmentation.

Analysis of Variance↗
PubMed1998

Encoding of three-dimensional structure-from-motion by primate area MT neurons.

We see the world as three-dimensional, but because the retinal image is flat, we must derive the third dimension, depth, from two-dimensional cues. Image movement provides one of the most potent cues for depth. For example, the shadow of a contorted wire appears flat when the wire is stationary, but rotating the wire causes motion in the shadow, which suddenly appears three-dimensional. The neural mechanism of this effect, known as 'structure-from-motion', has not been discovered. Here we study cortical area MT, a primate region that is involved in visual motion perception. Two rhesus monkeys were trained to fixate their gaze while viewing two-dimensional projections of transparent, revolving cylinders. These stimuli appear to be three-dimensional, but the surface order perceived (front as opposed to back) tends to reverse spontaneously. These reversals occur because the stimulus does not specify which surface is in front or at the back. Monkeys reported which surface order they perceived after viewing the stimulus. In many of the neurons tested, there was a reproducible change in activity that coincided with reversals of the perceived surface order, even though the stimulus remained identical. This suggests that area MT has a basic role in structure-from-motion perception.

Animals↗
PubMed1997

Multimodal representation of space in the posterior parietal cortex and its use in planning movements.

Recent experiments are reviewed that indicate that sensory signals from many modalities, as well as efference copy signals from motor structures, converge in the posterior parietal cortex in order to code the spatial locations of goals for movement. These signals are combined using a specific gain mechanism that enables the different coordinate frames of the various input signals to be combined into common, distributed spatial representations. These distributed representations can be used to convert the sensory locations of stimuli into the appropriate motor coordinates required for making directed movements. Within these spatial representations of the posterior parietal cortex are neural activities related to higher cognitive functions, including attention. We review recent studies showing that the encoding of intentions to make movements is also among the cognitive functions of this area.

Animals↗
PubMed1996

Mechanisms of heading perception in primate visual cortex.

When we move forward while walking or driving, what we see appears to expand. The center or focus of this expansion tells us our direction of self-motion, or heading, as long as our eyes are still. However, if our eyes move, as when tracking a nearby object on the ground, the retinal image is disrupted and the focus is shifted away from the heading. Neurons in primate dorso-medial superior temporal area responded selectively to an expansion focus in a certain part of the visual field, and this selective region shifted during tracking eye movements in a way that compensated for the retinal focus shift. Therefore, these neurons account for the effect of eye movements on what we see as we travel forward through the world.

Animals↗
PubMed1995

Integration of motion and stereopsis in middle temporal cortical area of macaques.

The primate visual system incorporates a highly specialized subsystem for the analysis of motion in the visual field. A key element of this subsystem is the middle temporal (MT) cortical area, which contains a majority of direction-selective neurons. MT neurons are also selective for binocular disparity (depth), which is perplexing given that they are not sensitive to motion through depth. What is the role of disparity in MT? Our data suggest an important link between disparity and transparent motion detection. Motion signals in different directions tend to inhibit each other within a given MT receptive field. This inhibition has an averaging effect which minimizes MT responses to random motion signals created by light intensity changes and other non-motion stimuli (motion noise). But, in the absence of disparity cues, inhibition may also occur between surfaces moving in different directions through the same part of the visual field (transparent motion), thus impairing the detection of either surface. Here we show that inhibition in MT occurs mainly between motion signals with similar disparities. Transparent surface movements at different depths are thus represented independently in MT (that is, without inhibiting each other) whereas spurious motion signals from a given surface tend to cancel out. To our knowledge, these results provide the first evidence for a functional integration of motion and disparity in MT.

Animals↗
PubMed1995

OOPSEG: a data smoothing program for quantitation and isolation of random measurement error.

We describe a data smoothing program, OOPSEG, which automatically quantitates and filters the random measurement error in a given data series. The measurement error is initially guessed, and the Optimal Segments technique is used to filter a corresponding amount of variation from the data, thus generating a relatively smooth curve. The residuals about this smooth curve are tested for serial correlation. If correlation is detected, a new measurement error is guessed, and the data are filtered again. This process continues until a smooth curve has been found for which the residuals do not exhibit serial correlation. Such residuals represent the random component of the data, i.e. (presumably) the measurement error. The corresponding smooth curve thus approximates the original, error-free curve. The smooth curve and the estimated coefficient of variation of the data are returned. OOPSEG handles end effects by performing an expansion of the data set, smoothing this expanded data set, then deleting the artificial points before assembling the final, smooth curve. Also, data may be smoothed as a sequence of independent regions to accommodate time courses with known changes in experimental conditions. We suggest that OOPSEG may have numerous applications in data analysis and experimental design.

Algorithms↗
PubMed1994

Interictal language fluency in temporal lobe epilepsy.

Mild language production difficulties, particularly in confrontation naming, have been documented previously in patients with left temporal lobe epilepsy (LTLE). These difficulties, however, do not seem to be reflected in the conversational speech of these patients. In order to compare speech fluency in patients with left and right temporal lobe epilepsy (RTLE) experimentally, we studied global pause-to-speech ratios in patients with unilateral temporal lobe epilepsy, using cases with primary generalized epilepsy (PGE) as controls. We hypothesized that left-sides cases would exhibit longer pause durations than right-sided cases. Speech samples were elicited by asking subjects to describe five different New Yorker cartoons, with three repetitions of each description. Phonation was converted to graphic output, and pauses between 200 ms and 4000 ms were summated and divided by total phonation time. This measure did not discriminate significantly between the groups, although the LTLE group tended to pause longer than the RTLE or PGE groups. Increased variability in pause duration in the LTLE group during cycle 1 suggested that some individuals with LTLE are vulnerable to disruption when planning demands are high. A post hoc correlational analysis showed that variation in fluency was primarily explained by orthographically-based lexical retrieval, suggesting that individual differences in fluency are related to limitations in a high-level capacity relevant to the production of speech. It is unlikely that such limitations are specific to LTLE.

Adult↗
PubMed1993

Quantitation of measurement error with Optimal Segments: basis for adaptive time course smoothing.

We introduce a novel technique for estimating measurement error in time courses and other continuous curves. This error estimate is used to reconstruct the original (error-free) curve. The measurement error of the data is initially assumed, and the data are smoothed with "Optimal Segments" such that the smooth curve misses the data points by an average amount consistent with the assumed measurement error. Thus the differences between the smooth curve and the data points (the residuals) are tentatively assumed to represent the measurement error. This assumption is checked by testing the residuals for randomness. If the residuals are nonrandom, it is concluded that they do not resemble measurement error, and a new measurement error is assumed. This process continues reiteratively until a satisfactory (i.e., random) group of residuals is obtained. In this case the corresponding smooth curve is taken to represent the original curve. Monte Carlo simulations of selected typical situations demonstrated that this new method ("OOPSEG") estimates measurement error accurately and consistently in 30- and 15-point time courses (r = 0.91 and 0.78, respectively). Moreover, smooth curves calculated by OOPSEG were shown to accurately recreate (predict) original, error-free curves for a wide range of measurement errors (2-20%). We suggest that the ability to calculate measurement error and reconstruct the error-free shape of data curves has wide applicability in data analysis and experimental design.

Animals↗
PubMed1993

Dynamics of hepatic and peripheral insulin effects suggest common rate-limiting step in vivo.

This study compares the dynamics and sensitivity of hepatic and peripheral insulin action in conscious dogs. Glucose turnover was measured simultaneously by HOT GINF tracer methodology and by hepatic AV differences. SRIF was infused during euglycemic clamps to suppress endogenous insulin and glucagon secretion. Basal plasma glucagon levels were recreated by intraportal replacement (2 ng.min-1 x kg-1), and insulin was infused intraportally at 0, 3, 6, 10, or 20 pmol.min-1 x kg-1 for 3 h. Steady-state HGO and NHGO were suppressed by insulin with EC50s of 164 and 95 pM, respectively. As expected, these were lower than the EC50 for Rd stimulation (516 pM), demonstrating greater hepatic than peripheral insulin sensitivity. In contrast to sensitivity, dynamics for suppression of HGO and NHGO and for stimulation of Rd by insulin were indistinguishable: half-times averaged 43 +/- 5, 42 +/- 9, and 45 +/- 5 min, respectively (P > 0.77). For all three variables, the half-time of insulin effect was independent of insulin dose (P > 0.26). The striking similarity of the time courses for suppression of glucose production and stimulation of glucose uptake suggests that both effects are secondary manifestations of a single, rate-limiting phenomenon. We hypothesize this single gateway to insulin action is transendothelial insulin transport, which we previously have shown to be rate limiting for insulin's effect on glucose uptake in vivo.

Animals↗
PubMed1992

Restoration of stable metabolic conditions during islet suppression in dogs.

These studies were undertaken to examine the stability of metabolic conditions during islet suppression with fixed-rate insulin and glucagon replacement. Somatostatin was infused peripherally at 0.8 microgram.min-1.kg-1, insulin was infused intraportally at 200 microU.min-1.kg-1, and glucagon was infused intraportally at 0, 0.6, 1, 2, 5, or 20 ng.min-1.kg-1 in conscious overnight-fasted dogs. [3-3H]glucose was infused for measurement of glucose kinetics. During infusion, plasma insulin was 7.2 +/- 0.4 microU/ml. Plasma glucagon rose linearly with glucagon dose, achieving basal levels at 2 ng.min-1.kg-1 infusion (164 +/- 18 vs. basal = 182 +/- 57 pg/ml). Plasma glucose and hepatic glucose output (HGO) decreased from basal at doses 0, 0.6, and 1 ng.min-1.kg-1, increased from basal at doses 5 and 20 ng.min-1.kg-1, and remained close to basal at dose 2 ng.min-1.kg-1 (92 +/- 20 vs. basal = 99 +/- 3 mg/dl and 2.4 +/- 0.2 vs. basal = 2.7 +/- 0.2 mg.min-1.kg-1 for glucose and HGO, respectively; P greater than 0.47). Glucose clearance and blood lactate were also closely matched to basal at dose 2 ng.min-1.kg-1. Coefficients of variation during 2 ng.min-1.kg-1 glucagon infusion (last hour) were 3.4, 4.6, 4.9, and 4.7% for glucose, HGO, clearance, and lactate, respectively. These findings indicate that fasting metabolic conditions, as inferred from blood glucose, lactate, insulin, and glucagon levels, and the rates of glucose production and uptake can be recreated in toto during fixed-rate islet hormone replacement.

Animals↗
PubMed1992

Hepatic glucagon sensitivity and fasting glucose concentration in normal dogs.

We assessed hepatic glucagon sensitivity in overnight-fasted, conscious dogs. Six pancreatic replacement protocols were performed in each of five animals. Somatostatin was infused to inhibit endogenous insulin and glucagon, insulin was replaced intraportally at 200 microU.min-1.kg-1, and glucagon was infused intraportally at 0, 0.6, 1, 2, 5, or 20 ng.min-1.kg-1. One intravenous glucose tolerance test was also performed in each animal for measurement of insulin sensitivity (SI). During hormone replacement at a given glucagon dose, plasma glucose differed substantially among animals (P = 0.003). Therefore the dose required for restoration of euglycemia ("glucagon requirement") varied nearly sevenfold among animals, suggesting appreciable differences in glucagon sensitivity (GS). The latter was quantitated in individual animals as the initial slope of integrated glucose output vs. glucagon concentration. GS varied from 0.22 to 3.9 mg.kg-1.pg-1.ml among various animals and was inversely and significantly related to glucagon requirement. SI varied less (approximately 4-fold) and was not associated with glucagon requirement. These observations suggested that interanimal differences in glucose during hormone replacement were the result of substantial differences in GS. In addition, we found the GS of a given animal to be highly associated (P = 0.01) with its fasting glucose level. We conclude that GS varies substantially, and as such may be an important determinant of the fasting glucose level in normal animals.

Animals↗