Journal of Neurophysiology

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Duration-Dependent Response of SI to Vibrotactile Stimulation in Squirrel Monkey

S. B. Simons, J. Chiu, O. V. Favorov, B. L. Whitsel, M. Tommerdahl


In previous studies, we showed that the spatial and intensive aspects of the SI response to skin flutter stimulation are modified systematically as stimulus amplitude is increased. In this study, we examined the effects of duration of skin flutter stimulation on the spatiotemporal characteristics of the response of SI cortex. Optical intrinsic signal (OIS) imaging was used to study the evoked response in SI of anesthetized squirrel monkeys to 25-Hz sinusoidal vertical skin displacement stimulation. Four stimulus durations were tested (0.5, 1.0, 2.0, and 5.0 s); all stimuli were delivered to a discrete site on the glabrous skin of the contralateral forelimb. Skin stimulation evoked a prominent increase in absorbance within the forelimb regions in SI of the contralateral hemisphere. Responses to brief (0.5 s) stimuli were weaker and spatially more extensive than responses to longer duration stimuli (1.0, 2.0, and 5.0 s). Stimuli ≥1 s in duration suppressed responses to below background levels (decreased absorbance) in regions that surrounded the maximally activated region. The magnitude of the suppression in the surrounding regions was nonuniform and usually was strongest medial and posterior to the maximally activated region. The results show that sustained (≥1.0 s) stimulation decreases the spatial extent of the responding SI cortical population. Registration of the optical responses with the previously documented SI topographical organization strongly suggests that the cortical regions that undergo the strongest suppression represent skin sites that are normally co-stimulated during tactile exploration.


We recently reported that an increase in the amplitude of a 10-s 25-Hz vibrotactile (“flutter”) stimulus to the skin on the forelimb does not lead to a larger region of increased activity in the contralateral SI (Simons et al. 2005). Instead, increased amplitude of a 10-s flutter stimulus was accompanied by increased activity within the same region activated at lower amplitude and by decreased activity in the surrounding region of SI. This result led us to consider the possibility that a stimulus parameter other than amplitude determines the magnitude and sign of activity expressed in surrounding cortex. The goal of this study was to characterize, using optical intrinsic signal (OIS) imaging, the SI response evoked by different durations of vibrotactile stimulation. The results reported in this paper show that, unlike longer duration flutter stimuli, a brief (≤0.5 s) flutter stimulus does not evoke a decrease in the activity in the regions of SI that surround the maximally responding region. The results raise the intriguing possibility that the spike discharge activity of neurons in the SI regions in which the optical response is suppressed by longer duration (>1.0 s) flutter stimuli is inhibited to an extent, and with a time-course consistent with, the magnitude and time-course of the stimulus-evoked suppression of the OIS.


Subjects and preparation

All methods and procedures are consistent with USPHS policies and guidelines on animal care and welfare in biomedical research. They were reviewed and approved by an institutional committee before initiation of the experiments. Experiments were conducted in five squirrel monkeys. After induction of anesthesia with 4% halothane in a 50/50 mix of N2O and oxygen, the trachea was intubated. A veterinary anesthesia machine (Forreger Compac-75) provided an anesthetic gas mix whose composition could be adjusted (typically 1.5–3.0% halothane in 50/50 N2O/oxygen) to maintain a stable level of surgical anesthesia. Methylprednisolone sodium succinate (20 mg/kg) and gentamicin sulfate (2.5 mg/kg) were injected intramuscularly to lessen the probability of halothane-induced cerebral edema and prevent bacterial septicemia, respectively. Placement of a valved polyethylene catheter into a superficial hindlimb vein enabled administration of 5% glucose, 0.9% NaCl, and drugs.

A 1.5-cm opening was trephined in the skull overlying SI cortex. A recording chamber (25 mm ID) was placed over the opening and cemented to the skull with dental acrylic. Wound margins were infiltrated with local anesthetic, closed with sutures, and bandaged, and the dura overlying the SI was resected. After the completion of all surgical procedures, subjects were immobilized with norcuron (loading dose, 0.25–0.5 mg/kg iv; maintenance dose, 0.025–0.05 mg/kg/h). From this point, the animal was ventilated with a 50/50 mix of N2O and oxygen, and the concentration of halothane was adjusted (typically between 0.5 and 1.0%) to maintain heart rate, blood pressure, and the EEG at values consistent with general anesthesia. Rate and depth of ventilation were adjusted to maintain end-tidal CO2 between 3.0 and 4.5%. Under these experimental/anesthetic conditions, SI neuron spontaneous and stimulus-evoked spike discharge activity patterns are highly reproducible over prolonged (>1 h) time periods.

Imaging and stimulus protocols

After obtaining an image of the exposed cortical surface, the recording chamber was filled with artificial cerebrospinal fluid and hydraulically sealed using a clear glass plate. Stimulus protocols were delivered in blocks of 100 trials (typically 20 trials per stimulus condition). All flutter stimuli (25 Hz) were 200 μm and were delivered to the glabrous skin of the contralateral forelimb with a vertical displacement stimulator (Cortical Metrics, Chapel Hill, NC). Four stimulus durations were tested (0.5, 1.0, 2.0, and 5.0 s) and interleaved with an intertrial interval of 60 s. A no-stimulus control condition was also interleaved with experimental test conditions. The imaging system consisted of a computer-interfaced CCD camera (Cascade 512b, Roper Scentific), light source, guide, and filters required for near-infrared (830 ± 25 nm) illumination of the cortical surface, a focusing device, and a recording chamber capped by an optical window (for additional methodological details, see Tommerdahl et al. 1999a,b). Images of the exposed anterior parietal and surrounding cortical surface were acquired 250 ms before stimulus onset (reference images) and continuously thereafter for 9.75 s after stimulus onset (poststimulus images) at a rate of one image every 250 ms. Difference images were generated by subtracting the reference image from each poststimulus image. Averaged difference images typically show regions of both increased light absorption (decreased reflectance) and decreased light absorption (increased reflectance), which are widely believed (Grinvald 1985; Grinvald et al. 1991a,b) to be accompanied by increases and decreases in neuronal activation, respectively.

All images were examined before their inclusion for analysis. Images containing random high-amplitude noise were excluded, and the remaining trials (typically 10–15 were averaged to improve the signal to noise ratio). Images were analyzed using custom routines written in Matlab.

Near-infrared OIS imaging

The OIS recorded from SI cortex is an indirect reflection of both neuronal spike discharge activity and the local, subthreshold changes in neuronal membrane potential evoked by sensory stimulation (Holthoff and Witte 1996; Kohn et al. 2000; MacVicar and Hochman 1991). Unfortunately, because the exact manner in which the OIS relates to the underlying electrical response of neurons remains poorly understood, changes in the magnitude of the OIS may not necessarily indicate a corresponding increase or decrease in single or multi-neuron electrical activity. In this study, we acquired the OIS at a wavelength of 830 nm. The OIS obtained using 830-nm illumination has been shown to be highly correlated with light scattering effects that accompany astrocytic swelling subsequent to the clearance of extracellular K+ and neurotransmitter (Holthoff and Witte 1996; Kohn et al. 2000; Lee et al. 2005) and local increases in blood volume (Ba et al. 2002; Frostig et al. 1990). Although the OIS at this wavelength is influenced to some extent by changes in local hemoglobin concentration and oxygenation, it is likely that the contributions from these sources are small compared with light-scattering effects (Ba et al. 2002; Lee et al. 2005). Furthermore, although the OIS recorded using near-infrared illumination is smaller in magnitude than the OIS recorded at lower wavelengths, it minimizes the contributions of artifacts introduced by hemodynamic changes that can dominate the OIS at lower wavelengths (Frostig et al. 1990), and thus is more appropriately suited for examining spatial attributes of the cortical neuroelectrical response to peripheral stimulation of skin mechanoreceptors (Ba et al. 2002).

Response recovery

Because of the technical demands encountered in the acquisition and analysis of imaging data, there are inevitable tradeoffs between temporal and spatial resolution. The focus of this report is the spatial sharpening of the SI response that accompanies repetitive skin stimulation, and we thus chose to maximize spatial resolution over a shorter (10 s) interval. This enabled us to maximize the temporal resolution of the imaging data in the immediate vicinity of the skin stimulus. As a result, recovery of the OIS to prestimulus levels was not observed for the responses of SI to 5.0-s stimulation. Previously we showed that a 200-μm flutter stimulus applied to the skin for 10.0 s recovered to prestimulus baseline ∼8.0 s after stimulus offset (Simons et al. 2005). Similarly, Cannestra et al. (1998) reported that optical responses to 3.5- and 10.0-s stimuli exhibit intervals of reduced responsivity of 7.0 and 8.0 s, respectively: an outcome likely attributable to incomplete recovery. Although precise determination of the time required for full recovery was not shown in this study, all responses recorded recovered to prestimulus levels within the 60-s no-stimulus interval in all experiments.

Determination of region of interest

The region of interest (ROI) was defined for each stimulus location using the following procedure. Evoked responses to 5-s stimulation were summed over the duration of the stimulus. The maximally responding region was segmented along its anterior/posterior axis and absorbance was measured in 40 × 200-μm bins along the line. Segmentation through the maximally responding region typically reveals a Gaussian-like distribution of absorbance values, which steadily decrease (usually to below baseline values) as distance from the maximal response is increased. Borders of the ROI were defined by the edges of regions of increased absorbance, which in the case of thenar stimulation are consistently characterized by a circular region of ∼2 mm diameter as indicated by the dashed circle in Fig. 2.

FIG. 1.

Difference images evoked by stimulation of the contralateral thenar pad in 2 exemplary subjects. Reference images show vasculature and location of central sulcus (CS) on cortical surface. Anatomical orientation is indicated by crosshair schematic to the right. Difference images were generated by summing all images acquired over the duration of response. Responses to 0.5-, 1.0-, 2.0-, and 5.0-s stimuli as well as a no-stimulus control (summed over the same interval as the 5.0-s stimulus) are shown. Images have been spatially filtered using an averaging filter with a 3-pixel kernel size for easier visual identification of regions of activation.

FIG. 2.

Absorbance time-course in 1 subject. Left: difference image of response to 5-s stimulation from Fig. 1. Region of interest (ROI) was defined as the 2-mm diameter circular region shown by red dashed circle. Right: pixels lying within ROI were averaged for each frame and plotted as a function of time. Stimulus timing is indicated by lines under plots that are matched with time-course of same color (0.5 s, black; 1.0 s, red; 2.0 s, green; 5.0 s, blue). The no-stimulus control (dashed black line) is plotted for comparison to test conditions.

Correlation maps

Correlation maps (Fig. 4) were constructed to characterize the spatiotemporal properties of the OIS response. This analysis method has been previously described in detail (Simons et al. 2005; Tommerdahl et al. 1999b). Briefly, maps were constructed by choosing a reference region within the imaged field and computing the intensity correlation rij between the slope of the (average) absorbance time course in a 4 × 4-pixel moving window at location (i, j) and the slope of the time-course within a reference region over the interval between stimulus onset and the time of peak response. The region selected as the reference was defined by a boxel (π mm2 area) centered on the ROI. Each pixel (i, j) on the correlation map is represented by a correlation coefficient rij (−1 < r < 1). Because the slope of the response within the ROI (used for correlation) is strongly positive, positive coefficients indicate locations where absorbance increases during this interval, whereas negative coefficients indicate locations of decreased absorbance.

FIG. 3.

Across-subjects absorbance time-course. Method of time-course analysis from Fig. 2 was performed on all subjects (n = 5), and resulting plots were normalized (according to peak absorbance) and averaged. Stimulus timing is indicated by lines under plots, which are matched with time-course of the same color (0.5 s, black; 1.0 s, red; 2.0 s, green; 5.0 s, blue). No-stimulus control (dashed black line) is plotted for comparison to test conditions. Error bars represent between-subject SD after normalization.

FIG. 4.

Maps of correlated activity in 2 exemplary subjects. Image of exposed cortex at top left of each subject shows surface vasculature and anatomical orientation of SI. Correlation maps compare slope of average time-course in a 4 × 4-pixel moving window to slope of known time-course of ROI (2-mm-diameter region of maximal activity indicated by dashed circle) over interval from stimulus onset to peak response and assign a coefficient to show degree of correlation. Input signal used for correlation is shown below its respective map, with absorbance scaled according to percent change from baseline (y-axis) and time in seconds (x-axis). Pixels displaying positive coefficients have time-courses with positive slope (increased absorbance), whereas pixels displaying negative coefficients have time-courses with negative slope (decreased absorbance). Control conditions show a lack of correlated activity in the absence of stimulation. All maps, within a subject group, have been scaled to the same color map to facilitate comparison.

Radial histograms

Radial histograms (Fig. 5) were generated by averaging absorbance values of all pixels lying at an equal radial distance from the maximally responding center. All equidistant pixels were averaged over 1 s of the maximal response (as determined by time-course within the ROI), independently for each duration. Before averaging across subjects, plots were normalized according to peak absorbance. Error bars represent the across-subject SD after normalization. Every fifth error bar is shown.

FIG. 5.

Radial absorbance trends across subjects (n = 5). Using radial binning, absorbance values were averaged over 1 s of maximal response to each stimulus duration (determined using time-course) in all subjects. Responses were normalized according to peak absorbance of 5-s response and averaged. Error bars show between-subject SE. As stimulus duration is increased, absorbance increases at distances near center of maximally responding region and decreases in surrounding regions. Regions defined as center and surround are indicated on plot (center = 0–1 mm; surround = 1.5–2.5 mm).

Surround anisotropy plots

Surround anisotropy plots (SAPs; Fig. 6) were generated by measuring the average absorbance in 10° (36 total measurements) segments within a ring located between 1.5 and 2.5 mm outside of the center of the ROI over the 1-s interval during which the response was maximal. The region used to obtain an estimate of absorbance in the surround was identified as the territory of greatest below-background activity in radial histograms. Absorbance values were represented with vectors indicating both the intensity (vector length) and the location of the evoked absorbance. All vector lengths were normalized to the maximum vector length for the 5.0-s stimulus condition. Note that because vectors are normalized to the largest decrease in absorbance (negative values), vectors that are negative indicate an increase in absorbance. The longest vectors within a plot thus indicate locations of strongest suppression (decreased absorbance).

FIG. 6.

Surround anisotropy plots (SAPs) for 1 exemplary subject. Plots indicate directions of largest suppression (absorbance decrease) for each stimulus duration. Anatomical orientation of plots is indicated by schematic at top left (posterior = 0°, lateral = 90°, etc.). Absorbance was averaged in 10° increments at distances between 1.5 and 2.5 mm outside ROI center (as per Fig. 5) over a 1-s interval of maximal response. Each measurement is plotted as a vector displaying magnitude (indicated by vector length) and direction of absorbance change in surround. All vectors were normalized to minimum value obtained (in surround) in response to 5.0-s stimulation; thus vectors with positive values indicate negative absorbance.


Figure 1 shows the OIS difference images evoked in SI of the contralateral hemisphere for two subjects in response to five different stimulus conditions (4 stimulus and the no-stimulus control conditions). As stimulus duration was increased, the maximum absorbance increase evoked in SI of each subject became progressively more intense, and the borders of the ROI became visibly sharper.

Characterization of the temporal response within the maximally activated region

The time-course of the absorbance change was computed for stimulus-evoked responses differing only in duration (Fig. 2). The responses evoked by 0.5-, 1.0-, and 2.0-s stimuli displayed delayed responses typical of the intrinsic signal, with the peak of the response occurring at ∼2–3 s after stimulus onset, followed by the decay of the response to below-baseline levels between 5 and 6 s after stimulus offset. In striking contrast, the time-course of the absorbance change evoked by 5.0-s flutter stimulation corresponded much more closely to the timing of the flutter stimulus: i.e., with 5-s stimulation, the response steadily increased during stimulus delivery and decreased progressively after stimulus offset, although full recovery to prestimulus levels was not observed in the 10-s period during which data were acquired.

The across-experiment (n = 5) average time-course within the ROI under each duration of flutter stimulation is shown in Fig. 3. Plots were normalized with regard to the magnitude of peak absorbance in the 5.0-s response before averaging. The time-course of the responses to 0.5-, 1.0-, and 2.0-s stimuli are clearly distinguishable from the time-course of the response to 5.0-s stimulation. More specifically, the responses evoked by the 0.5-, 1.0-, and 2.0-s stimuli consist of an absorbance increase that corresponds closely with stimulus onset followed (after stimulus offset) by a relatively slower absorbance decrease. Similarly, the response to 5.0-s stimulation shows an initially rapid absorbance increase, followed by a slower absorbance increase that begins ∼3 s after stimulus onset (i.e., 2 s before stimulus off). Decay of the stimulus-evoked increase in absorbance occurred on a very similar time-course for the 0.5-, 1.0-, and 2.0-s stimuli and for these stimulus durations recovery to prestimulus levels occurred at nearly the same time in all subjects. Additionally, the responses to the 0.5-, 1.0-, and 2.0-s stimuli included a decrease of absorbance to below-baseline values that became increasingly larger in magnitude as stimulus duration was increased. Similar to the data shown in Fig. 2 (obtained from a single subject), the recovery of absorbance to prestimulus levels was significantly slower to 5.0-s flutter stimulation than at all shorter stimulus durations; in fact, for no subject did the absorbance increase measured in response to 5.0-s stimulation recover to baseline values during the 10-s period during which data were acquired.

Changes in degree of correlated activity with increasing stimulus duration

Correlation maps provide an estimate of the stimulus-evoked increase or decrease in absorbance at every location in the image and thus enable in-depth examination of the spatiotemporal properties of the SI response to stimulation. Figure 4 shows a correlation map for each of the stimulus durations used in two subjects. The maps for the 0.5-s stimulus condition reveal large and spatially diffuse patterns of positively correlated activity, indicating the possibility that absorbance is increased in a cortical territory that extends well beyond the ROI. Furthermore, the maps of the response to the half-second stimulus reveal that in the vicinity of the ROI and in the surrounding regions, both the positive and negative correlation coefficients are small. Conversely, the maps computed for the responses to 1.0-, 2.0-, and 5.0-s stimuli display patterns of positively correlated activity within the ROI with significantly higher correlation coefficients (Fig. 4, color bar scale). The positively correlated activity observed in response to the longer stimulus durations is much more tightly bounded within the indicated ROI than that observed in the 0.5-s map. The regions surrounding the ROI in these maps consistently display negatively correlated activity that, while observed only rarely in the response to 0.5-s stimulation, is present in increasing amounts in response to 1.0-, 2.0-, or 5.0-s stimulation. The negatively correlated activity in the surrounding regions indicates locations of stimulus-evoked decreases in absorbance.

Effects of stimulus duration on spatial extent

The average across-subject (n = 5) radial histograms in Fig. 5 show that increasing stimulus duration evoked increasingly higher absorbance in regions most proximal to the maximally responding central region (the ROI) and progressively less absorbance, often below prestimulus levels (0), in the surround. Interestingly, 0.5-s stimulation evokes a broad, albeit weak, absorbance increase over the entire 3-mm radius of the imaged region.

Anisotropy in magnitude of surround suppression

Although radial binning provides an overview of the spatial profile of the evoked response and characterizes the approximate contrast between the center and the surround, it provides few details about the spatial distribution of the response within the surround. To more precisely identify the locations in the SI of strongest suppression (below baseline absorbance decrease), a new method of analysis was developed (SAP; see methods). SAPs use vectors to indicate the magnitude (represented by vector length) and anatomical location (represented by the orientation of the vector) of the evoked absorbance changes in regions of the surround located between 1.5 and 2.5 mm from the ROI center. Note that because the response in the surround is negative for the 5.0-s stimulus duration (used for normalization), vectors showing positive values indicate an absorbance decrease, whereas negative vectors indicate an absorbance increase. Figure 6 shows SAPs for one subject computed for each stimulus duration. The plots show that the average magnitude of suppression in surrounding regions increases with increasing stimulus duration. In addition to the increase in overall magnitude, the SAPs in Fig. 6 strongly suggest that the locations in SI of the stimulus-evoked suppression are different at different stimulus durations, although at all durations, it consistently was largest in a location posterior and medial to the maximally activated region (ROI) and consistently smaller in a location lateral to the ROI.

Characterization of the temporal response in the surround

The SAPs of Fig. 6 clearly show that the magnitude of the absorbance decrease in the surround is largest immediately medial and posterior to the region maximally activated by flutter stimulation of the contralateral thenar. The absorbance time-course was calculated for the posterior/medial surround (the red shaded region) shown in the difference image at the left of Fig. 7. Time-courses were normalized by peak absorbance within the maximally responding ROI to 5.0-s stimulation and averaged across all subjects (n = 5). Consistent with the maps of correlated activity, the 0.5-s stimulus produces a modest increase in absorbance in this region and does not decrease below baseline. In contrast, 1.0-, 2.0-, and 5.0-s stimulation each evoked decreases in absorbance, and the magnitude and rate of decay of those decreases varied systematically with increasing duration. The magnitude of the stimulus-evoked absorbance decrease became progressively larger with increasing stimulus duration, and whereas the average response evoked by either 1.0- or 2.0-s stimulation did not significantly decrease below baseline during stimulus delivery, the response evoked by 5.0-s stimulation decreased substantially during the stimulus. Perhaps the most striking observation was that the decrease in absorbance evoked in the surround region by different durations of stimulation persisted for significantly different times; for the 2.0- and 5.0-s durations, there was little or no recovery toward prestimulus activity levels within the 10 s during which data were acquired.

FIG. 7.

Time-course in medial/posterior region of surround. Time-course of absorbance change in surround was computed in regions of largest absorbance decrease, as indicated by SAPs in Fig. 6. Left: difference image of response to 5.0-s stimulation from Fig. 1. Absorbance was averaged within medial/posterior surround located 1.5–2.5 mm outside maximally responding center (red shaded region). Right: absorbance time-course of this region was computed in all subjects and over all durations tested. Stimulus timing is indicated by lines under plots that are matched with time-course of the same color (0.5 s, black; 1.0 s, red; 2.0 s, green; 5.0 s, blue). No-stimulus control (dashed black line) is plotted for comparison to test conditions. Plots were normalized according to peak absorbance (within ROI) and averaged. Error bars represent across-subject SD after normalization.

Stimulus site-specific suppression

To determine whether the distribution of surround suppression within SI is sensitive to changes in stimulus site, the responses evoked (in the same subject) by 5.0-s flutter stimulation of the tip of digit 2 (D2) and of the thenar eminence were compared. The OIS responses and SAPs obtained in response to flutter stimulation delivered to each site are shown in Fig. 8. As before, radial binning was used to identify the boundaries of regions of increased and decreased absorbance for stimulation of D2 (data not shown). Although strong SI suppression in a posterior/medial location was obtained using each stimulus condition, an additional strong suppression at an anterior location was evident with thenar stimulation, but this component of the response was much weaker with stimulation of D2. Additionally, stimulation of D2 evoked a stronger suppression in a location lateral to the ROI than was detected in the same location in response to thenar stimulation. Regions of strongest suppression are visible in the difference images provided under each plot in Fig. 8: in these images, suppressed regions appear as white patches located medial and posterior to the maximally responding region.

FIG. 8.

SAPs for 2 different stimulus sites in the same subject. Plots were computed for response evoked by 5.0-s stimulation of thenar eminence and tip of digit 2 in the same subject. Bottom left: anatomical orientation is indicated on image of exposed cortical surface. Top left: schematic showing anatomical orientation of SAPs. Top middle: SAP of 5.0-s thenar stimulation from Fig. 6 is shown for comparison. Bottom middle: optical intrinsic signal (OIS) response to 5.0-s thenar stimulation from Fig. 1. Top right: SAP of 5.0-s stimulation of tip of digit 2. Bottom right: OIS response to 5.0-s D2 stimulation.

Our observations that 1) the distribution of surround suppression evoked in SI by stimulation of a skin site is nonuniform and 2) this distribution alters when the site of skin stimulation is changed raise the possibility that the location of stimulus-evoked SI suppression is functionally relevant. Although precise identification of the topographic identity of the suppressed SI sites requires that detailed receptive field maps be obtained from each subject and under each stimulus condition, this was not done in this set of experiments. Nevertheless, a first approximation of the topographic identity of the SI region(s) suppressed during flutter stimulation was made by co-registration of the optical images (images showing the locations of both the maximal absorbance increase and maximal suppression) with published receptive field maps of the SI forelimb region in squirrel monkey (Sur et al. 1982).

To this end, SAPs were computed for 5.0-s flutter stimuli delivered to eight different skin sites on the forelimb (using the data obtained in multiple experiments). In most cases, SAPs generated in this way (Fig. 9) indicate that the direction of strongest suppression consistently is located posterior/medial to the maximally responding SI region. This preliminary approach to comparison of the optical response of SI and SI topographic organization strongly suggests that stimulation of the digit tips evokes strong suppression of the anterior parietal representation of the corresponding interdigital pads; conversely, stimulation of either the thenar or interdigital pads (specifically ID1 and 2) evokes a strong suppression within those SI regions that represent the corresponding digit tips.

FIG. 9.

Corresponding skin sites to locations of strongest suppression. Illustration at left summarizes method used to estimate skin sites represented by locations of suppression. Shown in box is thresholded (≥90% of maximum) response to 5.0-s thenar stimulation. Arrow that points posterior/medial from maximally responding region indicates region (as identified by SAP) of strongest suppression, which, based on estimates, corresponds to cortical locations representing digit 1, as shown on hand at bottom left inset. Schematic at right shows location of 8 different stimulus sites that were examined on the hand. Arrows point to predicted skin sites, enclosed by dashed circles, corresponding to locations of strongest suppression for each stimulus location. Stimulation of a digit tip seems to evoke strongest suppression in regions representing corresponding interdigital pad, whereas stimulation of an interdigital pad evokes strongest suppression in region representing tip of corresponding digit.


The results of this study show that 1) increasing the duration of a flutter stimulus, within the range of 0.5–5.0 s, evokes a progressively larger increase in absorbance within the SI territory that receives its principal input from the stimulated skin site and a decrease in absorbance that (with increasing stimulus duration) increases in magnitude in one or more neighboring regions; 2) a minimal duration of skin flutter stimulation, (≥0.5 and ≤1.0 s) is required to evoke a stereotypical SI response to skin flutter applied to the thenar eminence characterized by an ∼2-mm-diameter region of increased activity, bounded by one or more regions in which activity is at or below-baseline levels; and 3) at stimulus durations ≥1.0 s, absorbance in the region of SI that surrounds the maximally activated region is nonuniform, with the region undergoing the strongest suppression located anterior and/or posterior to the maximally activated region.

Peripheral and central effects of prolonged mechanoreceptor stimulation

Multiple animal studies have shown that repetitive stimulation is reliably accompanied by reductions in neuronal responsivity at both peripheral and central levels of the somatosensory nervous system. For example, such stimulation is accompanied by a sustained decrease in the responsivity of skin mechanoreceptors located in the vicinity of the stimulated skin region (Bensmaia et al. 2005), a long-lasting depression of the responsivity of neurons in the cuneate nucleus of the brain stem ipsilateral to the stimulus site (OMara et al. 1988), a decrease in the thalamic and cortical neuron firing rate (Chung et al. 2002), and a persistent reduction in the spatial extent of the SI region that responds to mechanical stimulation of a discrete skin site (Juliano et al. 1981, 1983). Kleinfeld and Delaney (1996) reported that a single mechanical stimulus evokes an increase in activity in an extensive region of barrel cortex but with repetitive stimulation the size of the responding region decreases significantly. Single unit studies and imaging studies using voltage-sensitive dyes likewise have shown that excitation in the responding neuronal population is accompanied by the development of a surrounding field of inhibition (Brumberg et al. 1996; Derdikman et al. 2003; Foeller et al. 2005; Wirth and Luscher 2004). Similarly, imaging studies that have used the OIS have shown that prolonged stimulation of a discrete skin site not only is associated with increased absorbance within the SI region representing the stimulated skin site, but also with decreases in absorbance in surrounding regions (Moore et al. 1999; Simons et al. 2005; Tommerdahl and Whitsel 1996; Tommerdahl et al. 1999a). Regions of decreased absorbance (increased reflectance) such as those reported in this study are widely believed to be indicative of decreases in neuronal spike discharge activity (Grinvald 1985; Grinvald et al. 1991a,b), possibly resulting from stimulus-evoked inhibition at these locations.

Stimulus site-specific SI suppression

The anisotropy in the distribution of suppression in the surrounding regions of SI leads us to suggest that this feature of the SI population response contributes importantly to sensorimotor function. Anisotropy in the distribution of surround inhibition has been previously reported in single-unit recordings obtained from the barrel cortex of the rat; Brumberg et al. (1996) reported that locations of strongest inhibition are aligned in a manner consistent with the anatomical orientation of the barrel field. The caudomedial orientation of this inhibition, relative to regions of excitatory activity, was subsequently confirmed by imaging studies using voltage-sensitive dyes (Derdikman et al. 2003). In this study, suppression of the SI intrinsic optical response was strongest at locations oriented in a highly specific way relative to the maximally responding region in SI. Furthermore, the distributions of these regions of suppression are stimulus site specific and thus provide more evidence that this suppression may be functionally significant.

Functional implications

Vierck et al. (1988) have shown that absolute tactile localization in behaving monkeys was better along the proximodistal axis than the mediolateral axis of the distal forelimb. If the perceptual ability to spatially localize a stimulus is a reflection of SI's ability to spatially discriminate stimuli at adjacent skin sites, the findings of Vierck et al. (1988) are in accord with the idea that stimulus-evoked inhibition acts to preferentially enhance the spatial separation of the SI responses to stimuli delivered to skin sites arranged along the proximodistal axis of the hand. Consistent with this prediction is this study's demonstration that flutter stimulation of a skin site evokes a strong below-baseline suppression of activity in SI territories that (based on comparision of our images of the stimulus-evoked OIS with published maps of SI topographic organization) represent skin sites displaced along the proximodistal axis of the hand. The observation that the areas of strongest suppression occur along the anterior/posterior axis of SI also identifies a plausible functional role for the high-density interareal connections reported by Burton and Fabri (1995). The results of this study support the idea that neuroanatomical connections that link columns in neighboring, but somatotopically distinct regions arranged in the anteroposterior dimension of SI play a crucial role in tactile acuity (Vierck et al. 1988).

The characteristic temporal development of the spatially patterned response of SI cortex to the long-duration tactile stimuli used in the experiments of this study is of interest because it leads to the prediction that if perceptual localization is based on activity in the contralateral SI, a prolonged (e.g., 5 s) tactile stimulus should enable significantly better performance than that measured when the stimulus is brief (0.5 s). For example, the experiments of this study showed that 1) delivery of a 5-s vibrotactile stimulus to the skin evokes an SI response that includes a persisting, suppressive component that occurs in the region of SI that surrounds the maximally activated region; a component that presumably reflects an inhibitory influence that would interfere with the SI response to a stimulus applied concurrently or subsequently to the skin region represented by neurons in that region of SI; and 2) brief (0.5 s) stimuli fail to evoke such a suppressive component. The results reported in a recent psychophysical study are in fundamental agreement with these predictions. That study observed the impact of a 0.5-versus 5.0-s adapting stimulus on a subject's ability to spatially localize a subsequent tactile stimulus. All subjects showed nearly a twofold improvement in spatial discrimination with a 5.0-s adapting stimulus (Tannan et al. 2006). These recently published psychophysical results, in combination with the findings of this study, suggest that the slow-to-develop but persistent suppressive responses observed in regions surrounding the maximally activated region of SI may underlie the recently observed (Tannan et al. 2006) adaptation-mediated improvements in the capacity of human subjects to localize the skin site contacted by a vibrotactile stimulus.

In primates, the hand is the primary means not only for tactile exploration of the environment, but also for voluntary manipulation of the environment. One example is a task involving grip requiring not only the coordination of hand and digit movement, but also the continuous incorporation of sensory feedback. We propose that the site-specific SI suppression that accompanies multisecond vibrotactile stimulation shapes the SI response to the inputs it receives from the multiple skin sites on the hand (e.g., the digit tips and corresponding interdigital pads) contacted either simultaneously or in rapid succession during tactile exploration and object manipulation. Further studies are needed to electrophysiologically confirm the presence and specificity of the stimulus-evoked inhibition inferred by the imaging results reported in this paper and to examine the impact of multisite stimulation on the spatiotemporal patterned SI response to mechanical stimulation of the skin.


This work was supported, in part, by National Institute of Neurological Disorders and Stroke Grants NS-43375 to M. Tommerdahl and NS-35222 to B. Whitsel and U.S. Army Research Office Grant P43077-LS to M. Tommerdahl.


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