[Comments on revision of framework plans].
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Biomedical subjects
Publications and source records attributed to K O Johnson.
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In the last decade or so, there has been rapid movement toward the use of more complex stimuli in the study of perceptual function related to the hand. This review has focused on the neural mechanisms of form and texture perception. Evidence from neurophysiological and psychophysical studies in which static touch, scanning touch, and the Optacon were used indicate that the spatial acuity of the RA system may be as much as three times poorer than the SAI system, evidence that suggests that form perception is dominated by the SAI system. Pattern recognition behavior in a tactual letter recognition task appears to be directly related to the response properties of SAI afferent fibers. Psychophysical studies of roughness perception show that roughness magnitude is related to surface structure in an orderly manner. Because roughness varies along an intensive continuum, mean impulse rate in one or more of the afferent systems is the most obvious coding possibility. No satisfactory relationship between mean impulse rate and roughness has been observed, however. The strongest hypothesis is that tactual roughness perception is based on spatial variation in the SAI population response. The combined evidence from studies reviewed here suggests complementary roles for each of the afferent systems, which are presented as working hypotheses: The SAI system is the primary spatial system and is responsible for tactual form and roughness perception when the fingers contact a surface directly and for the perception of external events through the distribution of forces across the skin surface. The PC system is responsible for the perception of external events that are manifested through transmitted high-frequency vibrations of the kind that are critical in the use of objects as tools. The RA system is responsible for the detection and representation of localized movement between skin and a surface as well as for surface form and texture when surface variation is too small to activate the SAI afferents effectively.
A previous study showed that roughness perception may depend on either temporal or spatial variations in firing rate among cutaneous mechanoreceptive afferents. The present study was designed to distinguish between these hypotheses. Plastic surfaces embossed with patterns of dots designed to produce predictable alterations in temporal and spatial firing rate variation were used as stimuli in psychophysical and neurophysiological experiments. Subjective roughness magnitudes obtained from psychophysical experiments fitted the predictions of the spatial but not the temporal hypothesis. In the neurophysiological experiments, the stimuli were scanned across the receptive fields of cutaneous mechanoreceptive afferents. Firing rate variation in the neural responses was measured using a range of temporal and spatial filters. Temporal variation was not correlated with roughness magnitude. Spatial variation, on a scale of 1-2 mm (one to two receptor spacings), was closely correlated with roughness.
The spatial resolving capacities of the four classes of mechanoreceptive afferents innervating human fingerpad skin were investigated to determine which class sets the limit of tactile spatial resolution for scanning stimuli. The stimulus consisted of an array of embossed dots (0.7 mm diameter, 0.5 mm high) arranged in a tetragonal pattern with dot spacing decreasing linearly from 6.4 mm at one end of the array to 0.87 mm at the other. The pattern was wrapped around a drum and repeatedly scanned across the receptive field of single afferents by continuously rotating the drum. Responses to many closely spaced scans were obtained by imposing a lateral shift of the pattern between each revolution. Impulses were recorded microneurographically. Responses were plotted in raster form to produce a neural image of the pattern. Responses of rapidly and slowly adapting type I (FAI and SAI) afferents resolved dots down to a spacing of about 1.5 mm. Responses of type II (FAII and SAII) afferents resolved dots down to a spacing of about 3.5 mm. Variation in scanning speed (range, 20-90 mm/sec) and contact force (range, 0.4-1.0 N) had minimal effects on spatial resolution of all afferents. The response clusters associated with individual widely spaced dots were used to investigate receptive field structure. FAI and SAI fields (mean areas, 6.1 and 4.8 mm2, respectively) each contained several zones of maximal sensitivity. FAI fields had five to eight such zones, whereas SAI fields had three to five such zones. As dot spacing decreased, neighboring dots interacted to affect the responses associated with the individual zones within a field. Initially, one or more zones were deactivated, effectively reducing receptive field size and allowing representation of finer spatial detail than would be predicted from the overall area of the receptive field. At very close dot spacings responses were only obtained when more than one sensitive zone within a field were simultaneously activated by different dots.
1. Subjects without any previous experience in a tactile psychophysics task participated in a study of tactile letter recognition employing active and passive touch. In the active task, subjects reached through a curtain and examined embossed letters with horizontal, unidirectional finger strokes. In the passive task, subjects sat with their arms and hands immobilized while a rotating drum stimulator pressed the embossed letters onto the right index finger. The stimulus conditions in the passive task were identical to those used in neurophysiological experiments with monkeys. 2. A survey of 40 naive subjects who were not screened in any way showed a wide range of performance levels. There was no difference between the subjects in the active and passive tasks, either in overall mean percent correct scores, which were 49.0 and 50.7%, respectively or in the percent correct scores for individual letters whose product-moment correlation coefficient was 0.94. The active and passive groups, which contained 25 and 15 members, respectively, had no members in common. 3. Videotapes of the finger movements of eight subjects in the active task showed a characteristic V-shaped velocity profile (velocity vs. lateral position) starting at approximately 100 mm/s at the left-hand edge of the plate containing the embossed letter, decelerating to a minimum when the center of the finger was directly over the letter, and then accelerating away from the letter. The average minimum scanning velocity was 17 mm/s. 4. Scanning velocity had no significant effect on performance in the passive task between 20 and 40 mm/s. An increase to 80 mm/s produced a 16% decline in percent correct identifications. 5. Learning effects were evident across sessions even though subjects were given no feedback or training. The increase in mean percent correct judgments averaged 4% per session, which lasted for approximately 1 h. 6. Data from 64 subjects were pooled for detailed comparison of identification patterns in active and passive touch. The results were analyzed and found to be consistent with the hypothesis that the identification and confusion probabilities are identical in the two modes. We conclude that there is no difference between active and passive touch in form recognition when the stimulus pattern is smaller than a finger pad. 7. Data from all experiments were pooled to produce a single confusion matrix with 324 presentations per letter. The majority of erroneous responses are grouped in a small number of confusion pairs and the majority of those confusion pairs are strongly asymmetric. The probable neural mechanisms of some confusion patterns are discussed.
We have used microneurographic techniques in human subjects to record mechanoreceptive afferent responses to standard Braille characters scanned across the finger pads. Responses from all four mechanoreceptor classes (FA I, FA II, SA I and SA II) have been reconstructed to form two-dimensional Spatial Event Plots (raster plots) of the Braille alphabet. Both the SA I and FA I responses resolve the dot patterns of Braille characters with sufficient fidelity that the representations of the individual characters can be recognized visually. Responses from SA II and FA II afferents do not resolve the Braille characters. We believe that the Spatial Event Plots derived from SA I and FA I responses closely approximate the images that are transmitted within a human nerve during Braille reading.
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Hypothetical neural codes underlying the sensation of tactile roughness were investigated in a combined psychophysical and neurophysiological study. The stimulus set consisted of plastic surfaces embossed with dot arrays of varying dot diameter and center-to-center spacing. Human subjects explored each surface with the pad of the index finger and reported their subjective sense of roughness magnitude. The same surfaces were scanned across the receptive fields of cutaneous mechanoreceptive afferents in monkeys while recording the evoked action potentials. Hypothetical neural codes for roughness magnitude were computed from the neural response patterns and tested for their ability to account for the psychophysical data. The psychophysical results showed that subjective roughness magnitude is an inverted U-shaped function of dot spacing that peaks near 3.0 mm spacing, and that increased dot diameter produces decreased roughness sensations at all dot spacings. Hypothetical neural codes that do not bear a consistent relationship to roughness magnitude across all of these stimulus conditions can be rejected as the code for roughness. Four types of neural codes were considered. They were based on (1) mean firing rate, (2) general variation in firing rate, (3) short-term temporal variation in firing rate, and (4) local spatial variation in firing rate. Mean firing rate failed to explain the psychophysical results: surfaces that evoked the same firing rate often evoked very different roughness judgments. In contrast, neural codes based on firing-rate variation, especially in slowly adapting afferents, account for the psychophysical results.
A tactile stimulator is described that moves embossed or textured patterns tangentially across the skin. Patterns constructed by standard photoetching are mounted on the outer surface of a cylinder that rotates at a selected speed and is held in contact with the skin at a selected force. The stimulator operates in several modes to meet the different requirements of psychophysical and neurophysiological experiments. The features of note are (i) relatively small size and weight; (ii) flexible automated control of drum contact with the skin, angular velocity, axial position, and contact force; (iii) monitoring of drum angular and axial location to better than 10 micron accuracy; (iv) construction with commercially available devices; (v) electronic monitoring of skin contact; and (vi) rapid drum changes (2 seconds) during psychophysical or neurophysiological experiments.
Embossed letters, used previously in pattern recognition experiments in humans, were used to study the spatial patterns of neural activity evoked in peripheral fibers and cortical neurons in areas 3b and 1 of the primary somatosensory cortex of alert rhesus (Macaca mulatta) monkeys. The object was to investigate the representation and transformation of spatial information during the early stages of peripheral and cortical neural processing. Our method consisted of sweeping each letter of the alphabet across the skin repeatedly and constructing a two-dimensional plot (called a spatial event plot) of the action potentials evoked in afferent fibers and cortical neurons. By using this method, slowly and rapidly adapting primary afferents were shown to transmit isomorphic neural images of the letters. Although the slowly adapting images were more spatially acute, both populations conveyed images of sufficient quality to account for human psychophysical performance. In the cortical areas studied, the slowly adapting neurons of area 3b stood out for the acuity, complexity, and variety of their responses. Some of the spatial event plots for these neurons were isomorphic and at least as acute as those obtained from any primary afferent. Others were highly structured but nonisomorphic. The quality and variety of responses in area 3b slowly adapting neurons suggest that they play an important role in the processing of information underlying tactual pattern recognition. The rapidly adapting neurons of area 3b and all types of neurons in area 1 yield much less structured and differentiated responses.
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The neural mechanisms subserving the sense of touch set the limits for the acquisition of information regarding the spatial and temporal characteristics of stimuli impinging on the skin surface. The results of three different psychophysical experiments imply that the skin of the finger pad can resolve the elements of a stimulus separated by 0.9 mm when the stimulus is applied to the skin and held stationary. This resolution limit is only slightly improved (to about 0.7 mm) when movement between the stimulus and skin is allowed. Single-unit recordings from three classes of primary mechanoreceptive afferents in anesthetized monkeys shows that only one class, the slowly adapting afferents, resolve spatial detail of stationary stimuli near the resolution limit. In addition, slow adaptors appear to resolve moving stimuli (e.g., Braille-dot patterns) more effectively than do the other two classes. However, these observations do not explain the extraordinary capacity of the finger-pad skin for discriminating between fine textures. Neurophysiological evidence suggests that information about such textures (i.e., surfaces with spatial details below the resolution limit) may be conveyed by a code based on the relative engagement of the three receptor populations.
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The current status of the L5178Y/TK+/- leads to TK-/- mouse-lymphoma mutagenicity assay is described. Dose-survival-mutagenic response data are shown for 43 chemicals. Mutagenicity and cytotoxicity in the presence or absence of non-induced and/or Aroclor-induced rat-liver S-9 are compared for most of these chemicals, 25 of these for which usuable carcinogenicity data exist have been used to construct an approximately linear relationship between oncogenic potency in vivo and mutagenic potency in this system in vitro; linearity between these two endpoints extends over a greater than 100,000-fold range in potencies. Several carcinogens which are negative or difficult to detect in the standard Ames assay are mutagenic in this mammalian cell system. These include natulan, sodium saccharin (lot S-1022), p,p'-DDE (metabolite of DDT), dimethylnitrosamine, diethylnitrosamine and diethylstilbestrol. Characterization of the TK-/- mutants suggests that two mutagenic mechanisms contribute to their final yield. Large-colony TK-/- mutants probably represent point or gene mutations affecting the TK locus. In addition, a class of small-colony TK(/- mutants are described and characterized as being heritably growth-deficient; this and other properties suggest that these small-colony TK-/- mutants originate by a heritable and viable chromosomal aberration. Most carcinogens and mutagens tested produce both classes of TK-/- mutants in this system; the relative proportions of small- and large-colony mutants are both mutagen- and dose-dependent. Comparative studies have been done at the rapidly-expressing TK locus and the slowly-expressing HGPRT locus in these cells. Several carcinogens detected at the TK locus are non- or very weakly mutagenic at the HGPRT locus. This findings is consistent with the induction of slow-growing specific locus mutants by a chromosomal mechanism and their subsequent dilution during this long expression time.
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1. Three hundred fourteen warm fibers innervating the glabrous skin of the monkey's hand were isolated by dissection in the median and ulnar nerves in two species, Macaca mulatta and M. nemestrina. Fiber samples in the two species were functionally similar and uniform in their properties. Their mean conduction velocity of 1.2 m/s (SD 0.5; n = 50) implies that these warm fibers were all unmyelinated. 2. A parametric study of the responses of warm fibers to near-rectangular warming and cooling pulses applied to glabrous skin was completed using 104 fibers. At a steady base-line skin temperature (T-base) of 34 degrees C all these warm fibers responded to warming pulses in the intensity range 0--8 degrees C with a simple, uniform discharge, which reached a peak rate of 1.5--4.0 s after the onset of stimulation; subsequent decay in this discharge rate had a time constant of 5--12 s and was virtually independent of the intensity of the warm pulse. The intensity function was linear for most fibers when the interstimulus interval was 60 s or longer. At a T-base of 29 degrees C, warm fibers were less responsive, but the temporal profile of the response was similar to that at a T-base of 34 degrees C in the intensity range 4--8 degrees C, and the intensity function was again linear. 3. At a T-base of 39 degrees C the intensity function of each warm fiber was complex. Most fibers responded briskly to warming pulses of 2--4 degrees C: the response to more intense warming pulses, particularly when the skin temperature rose above 45 degrees C, was structured and reproducible, but varied greatly among different fibers. With some the discharge evoked was of very high frequency for a few seconds, and then ceased. More than 80% of the sample of warm fibers did not discharge at all in response to warming pulses, which raised the skin temperature to 50 degrees C or above. 4. The responsiveness of warm fibers to warming pulses was dependent on previous stimulation when the interstimulus interval was less than 60 s. This temporal suppression was precisely structured and was examined quantitatively for trains of warming pulses, each lasting 4.0 s and presented every 10 s. The pattern of suppressive interaction was similar in form to that previously reported for cold fibers innervating palmar skin. 5. A quantitative study of the receptive fields of individual warm fibers demonstrated a spatiotemporal response pattern, which is best described in terms of a focal receptor zone less than 1 mm in diameter surrounded by thermally conducting skin. The skin's thermal conductivity is paramount in determining the warm-fiber's receptive-field characteristics. 6. The responses of warm fibers to cooling pulses and to warming ramps are described.
1. Experiments were designed to answer the question: how well does a single warm fiber innervating the glabrous skin of the monkey's hand resolve incremental changes in the intensity of near-rectangular warming pulses applied to the fiber's receptive field? 2. In these experiments the measure of the warm fiber's capacity to resolve incremental changes in the intensity of successive warming pulses was termed the discriminable stimulus increment (DSI). The DSI is defined as that incremental difference in the intensity of a pair of warming pulses that could be resolved correctly, with a probability of 0.75, by comparing the fiber's responses to these two stimuli. In the specified conditions of the experiment, DSI = 0.67 sigma delta tau/(dR/dI) where sigma delta tau is the standard deviation of the difference in responses of the fiber to pairs of stimuli, and dr/dI is the fiber's sensitivity to incremental stimulus change. (dr/dI) was experimentally determined as the mean rate of change of the fiber's responses to incremental changes in the intensity of the warming pulse. 3. The DSI, as defined above, assumes that the basis for differentiating the stimuli in each pair was that the larger response in the fiber was in each instance generated by the more intense stimulus. A more general form of the DSI was also developed and used to examine the effects on intensity resolution of different discrimination rules that the brain might use. 4. In the experimental analysis the response measure of each warm fiber was the cumulative impulse count over successively longer segments of the stimulus period. With short integration intervals the DSI was high (i.e., intensity resolution was poor), but typically the DSI fell to a plateau level within 2.0--2.5 s of the onset of the warming stimulus. 5. The DSI was measured on 23 warm fibers in Macaca nemestrina for warming pulses with intensities of 0, 2, 4, 6, and 8 degrees C, at T-base levels of 29, 34 (near normal temperature of palmar skin), and 39 degrees C. For most observations the intensity resolution possible from the responses of single warm fibers, measured over this wide variety of stimulus conditions, was less than is achieved by the human observer trained to differentiate comparable warming pulses applied to the skin of the thenar eminence.
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