Faculty Bibliography

1. To measure spatial acuity of Pacinian corpuscle (PC) afferents in the median and ulnar nerves of macaque monkeys, we displayed horizontal bar patterns spaced 1-13 mm apart on a computer-controlled OPTACON stimulator contacting the hand. Two-point resolution was measured by simultaneously pulsing pairs of rows at rates of 100, 50, and 25 Hz; each pair was shifted in tandem across the skin in 1.2-mm steps to simulate tangential motion at speeds of 30-120 mm/s. Single-fiber responses are reported from eight physiologically identified PC afferents innervating the fingers and palm in anesthetized monkeys. 2. Pacinian afferents differ in their sensitivity to stripe patterns moved across the hand. Bursting PCs fire bursts of two or three spikes/pulse when one of the bars is close to the field center and one spike/pulse when adjacent bars straddle the center. These bursts result in double-peaked response profiles at stripe spacings greater than or equal to 2.4 mm. The passage of individual stripes over the field center is therefore represented by bursts of impulses superimposed on a continuous spike train. Unfortunately, many of these fibers also demonstrate fluctuations in firing that appear unrelated to the stripe pattern and therefore obscure its clear representation. 3. The remainder of the PC population displays uniform-sensitivity responses that resemble those previously reported for rapidly adapting (RA) afferents. They fire one spike/pulse as long as at least one of the bars is contained within the field. They merge individual stripes spaced less than one field diameter apart and show a pause in firing at wider spacing. Spatial resolution of gaps in the stripe pattern is therefore determined by receptive-field diameters, which extend up to 9.6 mm when tested with the OPTACON. 4. PCs display poorer spatial resolution than RAs, because of their larger receptive fields and less regular firing patterns. Only two of eight PCs tested demonstrated a pause in activity representing the gap between bars spaced 4.8 mm apart, whereas 11 of 14 RAs ceased firing briefly between stripes. Resolution of the individual stripes by all of the PCs tested was observed only at bar spacings of 1 cm (8 rows) or more. Spatial resolution of stripes is further impeded by the tendency of PC afferents to summate inputs from stripes spaced less than 2.4 mm apart; this results in response profiles with a single, large-amplitude broad peak.(ABSTRACT TRUNCATED AT 400 WORDS)

1. The contribution of rapidly adapting (RA) mechanoreceptors to two-point discrimination has been evaluated by examining their ability to resolve the spacing of grating patterns shifted across the skin. The experiments test two different neural coding mechanisms that have been proposed to underlie resolution of spatial detail on the hand: 1) a rate-intensity code in which the spacing of surface features is encoded by the average frequency of firing of individual sensory afferents, and 2) an isomorphic representation of shape in which variations in the firing patterns of individual afferents reflect the spatiotemporal profile of skin indentation. 2. To measure the spatial acuity of RA mechanoreceptors innervating the hands of macaque monkeys, we displayed pairs of horizontal bars spaced 1-13 mm apart on a computer-controlled OPTACON stimulator placed over glabrous skin. Two-point resolution was measured by simultaneously pulsing pairs of rows at rates of 100, 50 and 25 Hz; each pair was shifted in tandem across the hand to simulate lateral motion. Single-fiber recordings were made from physiologically identified RA afferents in anesthetized monkeys. 3. Receptive field diameter appears to be the critical determinant of spatial resolution of gaps between two bars. RAs fire continuously if bar spacing is less than the field diameter but do not summate inputs when both active rows are contained within the field. Response profiles evoked by two bars spaced less than 4.8 mm apart can be predicted from the single-bar profiles, assuming occlusion between overlapping inputs with the strongest member dominating axonal output. Two-thirds of the RAs tested discharge 1 spike/pulse as bar patterns cross the field, yielding a uniform spike train whose frequency reflects stimulus pulse rates but fails to indicate gaps between bars. An additional 17% fire 2 spikes/pulse when the bars contact or straddle the field center, but also fail to differentiate individual stripes spaced less than 3.6 mm apart. 4. Only 17% of RAs represent gaps narrower than the field diameter. These fibers show double-peaked response profiles to bar patterns spaced at least 2.4 mm apart, firing 2 spikes/pulse as first one, and then the second stripe crosses the field center. Timing between peaks corresponds to bar spacing. Responses are reduced in amplitude when adjacent bars straddle the field center, as occlusion between simultaneous inputs prevents summation of inputs from the two stimuli. Fifteen of 16 RAs failed to resolve bars spaced 1.2 mm apart, as double-spike responses were evoked only by the leading stripe.(ABSTRACT TRUNCATED AT 400 WORDS)

1. These experiments assay the functional significance of receptive-field architecture for information processing. Rapidly adapting (RA) afferents have been previously shown to converge information from clusters of 14-25 Meissner's corpuscles, whereas afferents innervating Pacinian corpuscles (PCs) have only a single, large receptor terminal. We tested two opposing hypotheses of functional architecture: 1) summation models, in which an afferent integrates signals from all of its terminals, showing monotonic increases in activity as a function of contact area, and 2) winner-take-all models, in which the most strongly activated receptor in the cluster dominates axonal output by cancellation of signals from other branches. 2. Bar and stripe patterns have been swept across the finger or palm of the monkey's hand at speeds of 30-120 mm/s with the use of a computer-controlled grid of sequentially activated miniature probes (OPTACON stimulator). The dense packing of OPTACON probes permits placement of up to five groups of stimulators within an individual receptive field, allowing us to activate one or more clusters of Meissner's corpuscles simultaneously and to stimulate the bulbar corpuscle of PC afferents at different orientations through the skin. Integration of information from moving bar patterns has been tested with two protocols. In the variable width protocol, the total number of activated rows in the pattern is varied from one to five, with a constant spacing of 1.2 mm between pulsed rows. In the variable density protocol, the length of skin stimulated is held constant at 5 mm and the spacing of stimuli varied. 3. RA afferents show no evidence of summation of inputs within their receptive fields. Motion of wide bars across the field increases the duration of firing but not the total spikes evoked by each pulse. Responses to the leading edge of wide bars were found to be identical to those evoked by a single-row bar. Simultaneous activation of two to five rows evokes the same or fewer spikes per pulse than the most effective individual row tested alone. When broad-bar patterns are centered over the field, contacting the maximum number of receptors, RAs follow activity in the dominant branch or terminus, suppressing additional inputs. Lack of summation is observed at all pulse frequencies tested (25-100 Hz). 4. Moving bar patterns evoke responses as long as at least one row stimulates the receptive field; broader patterns evoke longer spike trains whose total number of impulses is proportional to bar width.(ABSTRACT TRUNCATED AT 400 WORDS)

1. Tactile discrimination of form requires motion of the hand across the object scanned. To dissociate lateral distortion of the skin from neuronal processing mechanisms involving multiple receptor classes and parallel central networks, we have simulated motion of bar patterns across the fingers and palm by the use of a computer-controlled grid of sequentially activated probes (OPTACON stimulator). Horizontal bar patterns have been swept across the hand at speeds of 30-120 mm/s to quantitatively characterize responses of cutaneous mechanoreceptive afferents recorded in the median and ulnar nerves. 2. Mechanoreceptors with phasic responses to pressure are activated by spatial patterns on the OPTACON, whereas those with tonic pressure responses are not; moving-bar patterns strongly excite both Meissner's afferents [rapidly adapting (RA) mechanoreceptors] and Pacinian corpuscles (PCs) but fail to excite slowly adapting (SA) afferents. OPTACON-type stimulators thus allow selective activation of phasic mechanoreceptor channels with spatially complex stimuli. 3. RA afferents respond in an all-or-none fashion to activation of two to five adjacent rows spanning 1-5 mm on the finger, with nearly identical latencies on all trials; response profiles are remarkable for their regularity and reproducibility. PCs have larger fields (4-13 rows) and stronger but more irregular responses than RAs. 4. Uniform sensitivity throughout the receptive field is a consistent feature of RA responses. Individual mechanoreceptor terminals appear to have equal access to the spike initiation zone and provide the same amplitude input as the fiber discharges 1 spike/pulse at each field location in 75% of the RAs tested. Uniform sensitivity allows each afferent to transmit a repetitive signal of the parameter of interest such as object speed, contour, or texture. 5. One-quarter of RAs fire two spikes to probe indentation and retraction at the field center. Such graded responses are usually observed in only one direction of motion, reflecting a preferred sequence of receptor activation rather than a specific location on the skin. PCs fire bursts of two to four spikes throughout most of their receptive fields; sensitivity is broadly distributed rather than peaked. Thus phasic mechanoreceptors fail to provide a precise signal of stimulus location; localization at the level of individual papillary ridges appears to be signaled by a population mechanism involving unique combinations of RA, SA, and PC afferents.(ABSTRACT TRUNCATED AT 250 WORDS)

Tardive dyskinesia (TD) is thought to result from nigrostriatal dopaminergic supersensitivity secondary to prolonged neuroleptic exposure. Preclinical studies have demonstrated that the opiate antagonist naloxone can acutely reverse a haloperidol-induced hyperdopaminergic state. In a trial of high-dose naloxone, 20 patients with TD received i.v. naloxone (20 mg, 40 mg, and placebo) under double-blind conditions. At baseline and at regular postdrug intervals, patients were evaluated using a battery of motor, clinical, and neuropsychological measures to study effects on neurological, behavioral, and cognitive functions. There was a significant improvement in involuntary movements at 30 min postnaloxone, together with improvement in clinical ratings at that time point, as well as some cognitive changes. The implications of these findings for the putative functional relationship between dopaminergic and enkephalinergic systems in the nigrostriatal area are discussed

Neurons in somatosensory cortex of primates process sensory information from the hand by integrating information from large populations of receptors to extract specific features. Tactile neurons in areas 1 and 2 are shown to select features such as contact area, edge orientation, motion across the skin, or direction of movement. Features coded by kinesthetic neurons in areas 3a and 2 relate to joint movement, the joint angle around which the movement occurs, or coordinated postures of the hand and arm. An even higher order cortical cell integrates tactile and kinesthetic information; these 'haptic neurons' respond optimally to contact of objects actively grasped in the hand. These global features are coded at the expense of loss of information concerning fine-grained spatial detail

In order to classify movement-sensitive neurons in SI cortex, and to estimate their relative distribution, we have developed a new simple method for controlled motion of textured surfaces across the skin, as well as a set of objective criteria for determining direction selectivity. Moving stimuli were generated using 5 mm thick precision gear wheels, whose teeth formed a grafting. They were mounted on the shafts of low-torque potentiometers (to measure the speed and direction of movement) and rolled manually across the skin using the potentiometer shaft as an axle. As the grafting wheel was advanced, its ridges sequentially contacted a specific set of points on the skin, leaving gaps of defined spacing that were unstimulated. This stimulus was reproducible from trial to trial and produced little distention of the skin. Three objective criteria were used to categorize responses: the ratio of responses to motion in the most and least preferred directions [direction index (DI)], the difference between mean firing rates in the two directions divided by the average standard deviation [index of discriminability (delta'e)], and statistical tests. Neurons were classified as direction sensitive if DI greater than 35, delta's greater than or equal to 1.35 (equivalent to 75% correct discrimination by an unbiased observer), and firing rates in most- and least-preferred directions were significantly different (P less than 0.05). Good agreement was found between the three classification schemes. Recordings were made from 1,020 cortical neurons in the hand and forearm regions of primary somatosensory cortex (areas 3b, 1 and 2) of five macaque monkeys. Tangential motion across the skin was found to be an extremely effective stimulus for SI cortical neurons. Two hundred eighty six of 757 tactile neurons (38%) responded more vigorously to moving stimuli than to pressure or tapping the skin. One hundred twenty-one cells were tested with moving gratings and were classified according to their ability to differentiate movement in longitudinal and transverse directions. Responses to the moving gratings resembled those observed when stroking the skin with brushed, edges, or blunt probes. Three major types of firing patterns were found: motion sensitive, direction sensitive, and orientation sensitive. Motion-sensitive neurons (37%) responded to movement in both longitudinal and transverse directions with only slight difference in firing rates and interval distributions. Responses throughout the field were fairly uniform, and no clear point of maximum sensitivity was apparent. Direction-sensitive neurons (60%) displayed clear preferences for movement in one or more directions.4

In order to measure the texture coding capabilities of motion-, direction-, and orientation-sensitive neurons in SI cortex, we rolled wheels with surface milled gratings across their receptive fields. Gratings of spatial periods 0.8-9.6 mm were presented in pseudorandom order; each was tested 5-20 times in the distal, proximal, radial, and ulnar directions. Thirty eight cortical neurons were studied with three to eight different gratings in order to determine the effect of spatial period on neuronal firing rates. While all 38 cells had their firing rates modulated by motion of the gratings, only 11 neurons were able to distinguish changes in its spatial period. These cells had small receptive fields located on the hand. Most motion-sensitive neurons showed little effect of spatial period on firing rates and had relatively flat frequency response curves. One showed decreased firing to spatial periods over the range 0.8-6.4 mm; three others increased their firing rates over the range 0.8-3.2 mm, followed by a decline in activity to larger spatial periods. Direction- and orientation-sensitive neurons showed only minor changes in firing rates as a function of spatial period. Sixteen cells showed flat frequency response functions, three showed increased firing rates, and four decreased firing rates as spatial period of the grating increased. Direction and orientation preferences were maintained over the range 0.8-9.6 mm for all 23 neurons tested. Although four cells showed a drop in direction index (DI) as the spatial period was increased, none showed a loss of direction sensitivity, as DI was greater than 35 for all gratings tested. Two neurons showed increased firing to motion in the last-preferred direction and two others decreased firing in the best direction. The remaining 19 neurons showed parallel effects of texture in all directions. Some motion-sensitive neurons showed weak direction preferences when tested with fine gratings; these preferences disappeared with coarser gratings, due to increased responsiveness to motion in the least-preferred direction. These data demonstrate that movement-sensitive neurons do not require continuous trajectories across the skin but instead sequential activation of points aligned in a specific path. Cortical neurons appear capable of integrating information from points separated by up to 9 mm, as long as they are presented in the appropriate temporal sequence. Firing rates of direction- and orientation-sensitive neurons are more profoundly modified by changes in the direction of motion across the skin, and the temporal order of stimulation, than by alterations in the spatial characteristics of the moving stimulus.(ABSTRACT TRUNCATED AT 400 WORDS)

To compare the relative sensitivities of glabrous and hairy skin, we measured reaction times (RTs) and detectability (d') of airpuffs delivered to the hairy dorsum and glabrous thenar eminence of the hand of six human subjects. In contrast to previous studies with mechanical contact stimuli, airpuffs applied to hairy skin were detected with equal or greater fidelity than airpuffs tested on glabrous skin. Mean RTs to three simultaneously applied airpuffs were significantly shorter (p less than .005) on hairy skin in five of six subjects, and in 74% of paired sessions; no significant difference in mean RTs was observed in 16% of the sessions. The superiority of hairy skin was less evident, however, when single airpuffs were tested, as significantly shorter responses were observed on only 45% of the paired sessions, and nearly identical responses on 38% of the sessions. Detectability of airpuffs (d'), which is independent of the value of RTs, was identical on hairy and glabrous skin at high airpuff intensities (1,600 dyn), and superior (n = 4) or equal (n = 2) on hairy skin with low airpuff intensities (800 dyn). Spatial summation was more pronounced on hairy than on glabrous skin. Three simultaneously presented airpuffs produced significantly shorter RTs than one airpuff in 85% of the paired sessions on hairy skin, but on only half of the sessions on glabrous skin. The spatial distribution of stimulus force was less important on hairy skin, as three low-intensity airpuffs produced the same or shorter RTs than one high-intensity airpuff. By contrast, on glabrous skin, detectability was significantly better when force was concentrated at a single point (1 X 1,600 dyn) than when diffused over a wide skin area (3 X 800 dyn). The enhanced sensitivity of hairy skin to airpuffs appears partially attributable to hair motion in the airstream. After hair removal by chemical depilation, detectability of airpuffs was reduced on hairy skin to a level equal to or below that on glabrous skin. Spatial summation on the depilated skin corresponded to that observed on the intact hairy skin, indicating that depilation did not abolish intensity discrimination, but rather lowered the overall sensitivity of hairy skin. These results show that hair follicle units form a very sensitive detection mechanism on hairy skin of the human hand, similar to that provided by Meissner's and Pacinian afferents in glabrous skin. These findings with airpuffs provide the first example of a tactile stimulus that is less effective for mechanoreceptors in glabrous skin than in hairy skin.(ABSTRACT TRUNCATED AT 400 WORDS)