B. L. Whitsel

Role of primary somatosensory cortex in the coding of pain

The intensity and submodality of pain are widely attributed to stimulus encoding by peripheral and subcortical spinal/trigeminal portions of the somatosensory nervous system. Consistent with this interpretation are studies of surgically anesthetized animals, demonstrating that relationships between nociceptive stimulation and activation of neurons are similar at subcortical levels of somatosensory projection and within the primary somatosensory cortex (in cytoarchitectural areas 3b and 1 of somatosensory cortex, SI). Such findings have led to characterizations of SI as a network that preserves, rather than transforms, the excitatory drive it receives from subcortical levels. Inconsistent with this perspective are images and neurophysiological recordings of SI neurons in lightly anesthetized primates. These studies demonstrate that an extreme anterior position within SI (area 3a) receives input originating predominantly from unmyelinated nociceptors, distinguishing it from posterior SI (areas 3b and 1), long recognized as receiving input predominantly from myelinated afferents, including nociceptors. Of particular importance, interactions between these subregions during maintained nociceptive stimulation are accompanied by an altered SI response to myelinated and unmyelinated nociceptors. A revised view of pain coding within SI cortex is discussed, and potentially significant clinical implications are emphasized.

Spatial organization of the peripheral input to area 1 cell columns. I. the detection of 'segregates'

Extracellular single neuron recording methods are used to study the RFs of neurons comprising area 1 cell columns in unanesthetized Macaca fascicularis monkeys. The RF data obtained in approximately radial microelectrode penetrations demonstrate that the RFs of neurons located within the same area 1 cell columns can differ strikingly, and that it is common for neighboring neurons to possess RFs differing greatly in size or configuration. However, the RF variations detected within a typical area 1 cell mini-column (single cell radial column) appear to be substantially less than the variations observed for nearby neurons lying in different minicolumns. The RF data obtained from arrays of penetrations suggest that the skin representation in the forelimb region of area 1 is organized in a discontinuous, step-like fashion: as a mosaic of discrete 600 micron wide radial cell columns--segregates. Although the RFs of neurons of a segregate can vary substantially in size and configuration, they all share in common a single small area on the skin. The boundaries of a segregate can be mapped precisely because, unlike the situation for neurons located within the same segregate, some of the neurons located on opposite sides of a segregate boundary (belonging to different segregates) have non-overlapping RFs. Furthermore, it appears that within any given segregate there is no systematic shift in RF location as the electrode advances through a sequence of minicolumns. Systematic RF shifts occurred only when the electrode traversed the boundary between neighboring segregates.

Time Course and Action Spectrum of Vibrotactile Adaptation

In a series of experiments designed to explore the processes underlying adaptation of the sense of flutter-vibration, vibrotactile threshold was measured on the pad of the index finger, using Békésy tracking. Unadapted thresholds were first measured, for a number of frequencies (4-90 Hz) and contactor sizes (1-8 mm diameter). As expected, these measurements indicated the presence of (1) a Pacinian system possessing spatial summation and increasing in sensitivity, as frequency was raised, at the rate of 12 dB/octave; and (2) a non-Pacinian system showing little spatial summation, and with a frequency characteristic matching that of the NP I mechanism of Bolanowski et al. (1988). These baseline data of Experiment 1 guided the selection of stimulus parameters for subsequent experiments, in which threshold for a test stimulus was measured before, during, and after periods of vibrotactile adaptation. In Experiment 2, test stimuli of 10 Hz and 50 Hz were combined factorially with 30-dB SL adapting stimuli of the same two frequencies. When the test stimulus was 10 Hz, the two adapting frequencies were equally effective in raising threshold; however, when the 50-Hz test stimulus was used, the 50-Hz adapting stimulus raised threshold by a greater amount than did the 10-Hz adapter. These results confirm on the finger the independence of adaptation in Pacinian and non-Pacinian channels, a result previously established on the thenar by other workers. For all four frequency combinations, threshold rose exponentially with a time constant of 1.5-2 min. In Experiment 3, an action spectrum was determined, showing the adapting amplitude needed at each of a series of frequencies to raise the threshold of a 10-Hz stimulus by 10 dB; this spectrum was essentially flat from 30 to 90 Hz. The results, taken in conjunction with what is known about rapidly adapting cutaneous mechanoreceptors, imply that the effectiveness of an adapting stimulus is not determined solely by the amount of activity it generates in first-order afferents.

Amplitude-dependency of response of SI cortex to flutter stimulation

BackgroundIt is established that increasing the amplitude of a flutter stimulus increases its perceived intensity. Although many studies have examined this phenomenon with regard to the responding afferent population, the way in which the intensity of a stimulus is coded in primary somatosensory cortex (SI) remains unclear.ResultsOptical intrinsic signal (OIS) imaging was used to study the evoked responses in SI of anesthetized squirrel monkeys by 25 Hz sinusoidal vertical skin displacement stimulation. Stimuli were 10 sec duration with a 50 sec inter-stimulus interval. Stimulus amplitude ranged from 50 to 400 microns and different amplitudes were interleaved. Control levels of activity were measured in the absence of stimulation, and used to compare with activation levels evoked by the different stimulus amplitudes. Stimulation of a discrete skin site on the forelimb evoked a prominent increase in absorbance within the forelimb representational region in cytoarchitectonic areas 3b and 1 of the contralateral hemisphere. An increase in stimulus amplitude led to a proportional increase in the magnitude of the absorbance increase in this region of areas 3b and 1 while surrounding cortex underwent a decrease in absorbance. Correlation maps revealed that as stimulus amplitude is increased, the spatial extent of the activated region in SI remains relatively constant, and the activity within this region increases progressively. Additionally, as stimulus amplitude is increased to suprathreshold levels, activity in the surround of the activated SI territory decreases, suggesting an increase in inhibition of neuronal activity within these regions.ConclusionIncreasing the amplitude of a flutter stimulus leads to a proportional increase in absorbance within the forelimb representational region of SI. This most likely reflects an increase in the firing rate of neurons in this region of SI. The relatively constant spatial extent of this stimulus-evoked increase in absorbance suggests that an increase in the amplitude of a 25 Hz skin stimulus does not evoke a larger area of SI neuronal activation due to an amplitude-dependent lateral inhibitory effect that spatially funnels the responding SI neuronal population.

Dynamic representations of the somatosensory cortex

Neural representation of somatosensory events undergoes major transformation in the primary somatosensory cortex (SI) from its original, more or less isomorphic, form found at the level of peripheral receptors. A large body of SI optical imaging, neural recording and psychophysical studies suggests that SI representation of stimuli encountered in everyday life is a product of dynamic processes that involve competitive interactions at multiple levels of cortical organization. Such interactions take place among neighboring neurons, among local groups of minicolumns, among neighboring macrocolumns, between SI and SII, between Pacinian and non-Pacinian channels, and bilaterally between homotopic somatosensory regions of the opposite hemispheres. Together these interactions sharpen SI response to suprathreshold and time-extended tactile stimuli by funneling the initially widespread stimulus-triggered activity in SI into the local group of macrocolumns most directly driven by the stimulus. Those macrocolumns in turn fractionate into stimulus-specific patterns of differentially active minicolumns. Thus SI dynamically shapes its representation of a tactile stimulus by selecting among all of its neurons initially activated by the stimulus a subset of neurons with receptive-field and feature-tuning properties closely matching those of the stimulus. Through this stimulus-directed dynamical selection process, which operates on a scale of hundreds of milliseconds, SI achieves a more faithful representation of stimulus properties, which is reflected in improved performance on tactile perceptual tasks.

Ipsilateral Input Modifies the Primary Somatosensory Cortex Response to Contralateral Skin Flutter

We recorded the optical intrinsic signal response of squirrel monkey primary somatosensory cortex (SI) to 25 Hz vibrotactile (“flutter”) stimulation applied independently to the thenar eminence on each hand and also to bilateral (simultaneous) stimulation of both thenars. The following observations were obtained in every subject (n = 5). (1) Ipsilateral stimulation was accompanied by an increase in absorbance within the SI hand region substantially smaller than the absorbance increase evoked by contralateral stimulation. (2) The absorbance increase evoked by simultaneous bilateral stimulation was smaller (by ∼30%) than that evoked by contralateral stimulation. (3) The spatiointensive pattern of the SI response to bilateral flutter was distinctly different than the pattern that accompanied contralateral flutter stimulation: with contralateral flutter, the center of the responding region of SI underwent a large increase in absorbance, whereas absorbance decreased in the surrounding region; in contrast, during bilateral flutter, absorbance decreased (relative to that evoked by contralateral flutter) in the central region of SI but increased in the surround. The results raise the possibility that somatosensory perceptual experiences specific to bimanual tactile object exploration derive, at least in part, from the unique spatiointensive activity pattern evoked in SI when the stimulus makes contact with both hands. It is suggested that modulatory influences evoked by ipsilateral thenar flutter stimulation reach SI via a two-stage pathway involving interhemispheric (callosal) connections between information processing levels higher than SI and subsequently via intrahemispheric (corticocortical) projections to the SI hand region.

Sensory cortical dynamics.

Sensory cortical networks are commonly regarded as stable, changing only in the face of prolonged alteration of sensory input. There is increasing evidence, however, that the functional connectivity of cortical networks changes significantly, but reversibly, in response to conditions of sensory stimulation similar to those encountered in everyday life. In this review, we provide examples of sensory cortical dynamics at the single neuron and neural population levels. The dynamics detected at both levels of experimental observation suggest that a brief exposure (tens of milliseconds to tens of seconds) to sensory stimulation is accompanied by changes in the capacity of cortical networks to process and represent environmental stimuli. Candidate cellular mechanisms and the potential benefits of such stimulus-driven, rapid, and fully reversible sensory cortical dynamics are discussed.

Discrimination and Scaling of Velocity of Stimulus Motion across the Skin

The capacity of human subjects to discriminate and to scale the velocity of tactile brushing stimuli was assessed. Signal detection and classical psychophysical techniques were employed to estimate the Weber fraction over a wide range of velocities (from 1.5 to 140 cm/sec). In addition, free magnitude estimates of (1) the velocity and (2) the duration of moving tactile stimuli were obtained. It was found that human capacity to discriminate stimuli delivered to a 4 to 6-cm chord of skin on the dorsal forearm and differing in velocity remains grossly constant over the range of velocities tested and is relatively poor (i.e., the Weber fraction = 0.2-0.25). A simple power function (exponent = 0.6) satisfactorily describes the psychophysical relation (1) between the perceived and actual velocity and (2) between the perceived and actual duration of these stimuli. Since a direct proportionality between the reciprocal of a subjects estimate of duration and his or her estimate of velocity was observed, it is suggested that these two sensory attributes may reflect the operation of a neural mechanism sensitive to the duration of stimulation. Moreover, the data are inconsistent with the hypothesis that the subjects computed estimates of mean velocity from the ratio of perceived distance to perceived duration.

Area 3a Neuron Response to Skin Nociceptor Afferent Drive

Area 3a neurons are identified that respond weakly or not at all to skin contact with a 25-38 degrees C probe, but vigorously to skin contact with the probe at > or =49 degrees C. Maximal rate of spike firing associated with 1- to 7-s contact at > or =49 degrees C occurs 1-2 s after probe removal from the skin. The activity evoked by 5-s contact with the probe at 51 degrees C remains above-background for approximately 20 s after probe retraction. After 1-s contact at 55-56 degrees C activity remains above-background for approximately 4 s. Magnitude of spike firing associated with 5-s contact increases linearly as probe temperature is increased from 49-51 degrees C. Intradermal capsaicin injection elicits a larger (approximately 2.5x) and longer-lasting (100x) increase in area 3a neuron firing rate than 5-s contact at 51 degrees C. Area 3a neurons exhibit enhanced or novel responsivity to 25-38 degrees C contact for a prolonged time after intradermal injection of capsaicin or alpha, beta methylene adenosine triphosphate. Their 1) delayed and persisting increase in spike firing in response to contact at > or =49 degrees C, 2) vigorous and prolonged response to intradermal capsaicin, and 3) enhanced and frequently novel response to 25-38 degrees C contact following intradermal algogen injection or noxious skin heating suggest that the area 3a neurons identified in this study contribute to second pain and mechanical hyperalgesia/allodynia.

Frequency-dependent response of SI RA-class neurons to vibrotactile stimulation of the receptive field

Three types of experiment were carried out on anesthetized monkeys and cats. In the first, spike discharge activity of rapidly adapting (RA) SI neurons was recorded extracellularly during the application of different frequencies of vibrotactile stimulation to the receptive field (RF). The second used the same stimulus conditions to study the response of RA-I (RA) cutaneous mechanoreceptive afferents. The third used optical intrinsic signal (OIS) imaging and extracellular neurophysiological recording methods together, in the same sessions, to evaluate the relationship between the SI optical and RA neuron spike train responses to low- vs high-frequency stimulation of the same skin site. RA afferent entrainment was high at all frequencies of stimulation. In contrast, SI RA neuron entrainment was much lower on average, and was strongly frequency-dependent, declining in near-linear fashion from 6 to 200 Hz. Even at 200 Hz, however, unambiguous frequency-following responses were present in the spike train activity of som