Departments of 1Biomedical Engineering and 2Cell and Molecular Physiology, University of North Carolina, Chapel Hill, North Carolina 27599
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ABSTRACT |
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Tommerdahl, M.,
B. L. Whitsel,
O. V. Favorov,
C. B. Metz, and
B. L. O'Quinn.
Responses of Contralateral SI and SII in Cat to Same-Site
Cutaneous Flutter Versus Vibration.
J. Neurophysiol. 82: 1982-1992, 1999.
The methods of
14C-2-deoxyglucose (14C-2DG) metabolic mapping
and optical intrinsic signal (OIS) imaging were used to evaluate the
response evoked in the contralateral primary somatosensory receiving
areas (SI and SII) of anesthetized cats by either 25 Hz ("flutter")
or 200 Hz ("vibration") sinusoidal vertical skin displacement
stimulation of the central pad on the distal forepaw. Unilateral 25-Hz
stimulation consistently evoked a localized region of elevated
14C-2DG uptake in both SI and SII in the contralateral
hemisphere. In contrast, 200-Hz stimulation did not evoke elevated
14C-2DG uptake in the contralateral SI but evoked a
prominent, localized region of increased 14C-2DG uptake in
the contralateral SII. Experiments in which the OIS was recorded
yielded results that complemented and extended the findings obtained
with the 2DG method. First, 25-Hz central-pad stimulation evoked an
increase in absorbance in a region in the contralateral SI and SII that
corresponded closely to the region in which a similar stimulus evoked
increased 14C-2DG uptake. Second, 200-Hz stimulation of the
central pad consistently evoked a substantial increase in absorbance in
the contralateral SII but very little or no increase in absorbance in
the contralateral SI. And third, 200-Hz central-pad stimulation usually
evoked a decrease in absorbance in the same contralateral SI region
that underwent an increase in absorbance during same-site 25-Hz
stimulation. Experiments in which the OIS responses of both SI and SII
were recorded simultaneously demonstrated that continuous (>1 s) 25-Hz central-pad stimulation evokes a prominent increase in absorbance in
both SI and SII in the contralateral hemisphere, whereas
only SII undergoes a sustained prominent increase in
absorbance in response to 200-Hz stimulation to the same central-pad
site. SI exhibits an initial, transient increase in absorbance in
response to 200-Hz stimulation and at durations of stimulation >1 s,
undergoes a decrease in absorbance. It was found that the
stimulus-evoked absorbance changes in the contralateral SI and SII are
correlated significantly during vibrotactile stimulation of the central
padpositively with 25-Hz stimulation and negatively with 200-Hz
stimulation. The findings are interpreted to indicate that 25-Hz
central-pad stimulation of the central pad evokes spatially localized
and vigorous neuronal activation within both SI and SII in the
contralateral hemisphere and that although 200-Hz stimulation evokes
vigorous and well maintained neuronal activation within the
contralateral SII, the principal effect on the contralateral SI of a
200-Hz stimulus lasting >1 s is inhibitory.
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INTRODUCTION |
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There is general agreement that in cats and monkeys (and presumably in humans) the spike discharge activity a mechanical stimulus sets up in rapidly adapting (RA), slowly adapting (SA), and Pacinian (PC) skin mechanoreceptors is projected centrally, at short latency and with relatively minor transformation, to primary somatosensory cortex (both SI and SII) in the contralateral hemisphere. There is no consensus, however, about the way in which the stimulus-evoked response in each area contributes to cerebral cortical somatosensory information processing and somatosensation.
According to current models, the principal source of the input that
enables SII to respond to contralateral mechanoreceptor afferent drive
is different in different species. In cats, for example, most input to
SII from the opposite side of the body is conveyed via thalamocortical
connections (the "in-parallel" model) (Rowe et al.
1996). In old world primates, however, the main input to SII
from the opposite side of the body is conveyed via corticocortical
axons arising in SI of the same hemisphere (the "serial" model)
(Burton 1995
; Pons et al. 1987
). While
the "in-parallel" or "serial" models of somatosensory
information flow account for the sources of input to SI and SII,
neither model addresses the important issue of whether, and to what
extent, the activity evoked in one cortical area by a skin stimulus is independent of the activity the same stimulus evokes in the other.
The experiments described in this paper are a component of the initial
stage of a program of research designed to obtain detailed information
bearing directly on this issue. To this end, the 2-deoxyglucose (2DG)
and optical intrinsic signal (OIS) imaging methods were employed to
evaluate the locus, form, magnitude, and time course of the responses
of SI and SII in the contralateral hemisphere of cats to 25 versus
200-Hz vertical displacement stimulation of the central pad. A recent
related study (Tommerdahl et al. 1999) described the
responses of contralateral anterior parietal cortex in squirrel monkey
to 25- and 200-Hz stimulation of the same skin site.
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METHODS |
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Subjects and preparation
Subjects were adult cats (males and females). All surgical procedures were carried out under general anesthesia (1-4% halothane in a 50/50 mixture of oxygen and nitrous oxide). After induction of anesthesia, the trachea was intubated with a soft tube, and a polyethylene cannula was inserted in the femoral vein to allow administration of drugs and fluids (5% dextrose and 0.9% NaCl). No further surgical manipulations were required in the subjects in which 2DG imaging was carried out. For each subject used for OIS imaging, a 1.5-cm-diam opening was made in the skull overlying somatosensory cortex, a chamber was mounted to the skull over the opening with dental acrylic, and the dura overlying anterior parietal cortex was incised and removed. All wound margins were infiltrated with long-lasting local anesthetic, the skin and muscle incisions were closed with sutures, and each surgical site outside the recording chamber was covered with a bandage held in place by adhesive tape.
Before (1-3 h prior to) the data acquisition phase of the
OIS-imaging experiments or to administration of
14C-2DG, subjects were immobilized with Norcuron
(vecuronium bromide; loading dose 0.1-0.5 mg/kg; 0.5 µg · kg1 · min
1
thereafter). At all times thereafter subjects were ventilated using a
50/50 oxygen and nitrous oxide mix; supplemented with 0.1-1.0%
halothane. Respirator rate and volume were adjusted to maintain
end-tidal CO2 between 3.0 and 4.0%;
electroencephalographic and autonomic signs (slow wave content; heart
rate, etc.) were monitored and titrated (by adjustments in the
anesthetic gas mix) to maintain levels consistent with light general
anesthesia. Rectal temperature was maintained (using a heating pad) at
37.5°C.
The cats were killed by intravenous injection of pentobarbital (45 mg/kg) and by intracardial perfusion with saline followed by fixative (10% formalin). After perfusion, fiducial marks were placed to guide removal, blocking, and subsequent histological sectioning of the cortical region studied. All procedures were reviewed and approved in advance by an institutional committee and are in full compliance with current National Institutes of Health policy on animal welfare.
Stimuli and stimulus protocols
In all but one of the 2DG and OIS-imaging experiments that provided the data reported in this paper, the mechanical stimuli used to evoke cortical activity were applied to the same site (a 5-mm-diam site in the center of the central pad of the distal forepaw) on the forelimb. In the one subject in which a skin site different from the central pad was stimulated (an experiment using the OIS-imaging method), the stimuli were applied to a 5-mm site on the hairy skin of the ventral ulnar forelimb at the level of the pisiform pad. The stimuli always consisted of sinusoidal vertical skin displacements applied using a servocontrolled transducer (Cantek Metatron, Canonsburg, PA).
Two frequencies of sinusoidal vertical displacement stimulation were
used in most experiments25 and 200 Hz. In the initial 2DG experiments
(3 subjects), one of the frequencies was delivered to one forepaw
central pad and the other frequency to the corresponding site on the
central pad of the opposite forepaw. In the second series of 2DG
experiments (2 subjects), 200-Hz stimulation was applied unilaterally
to the central forepaw. In all but one OIS-imaging experiments, the
stimuli (25 and 200 Hz) were delivered to the same skin site (the
central pad) used in the 2DG studies, and in every experiment the
different frequencies of stimulation were interleaved in the same
"run" on a trial-by-trial basis. To illustrate, in the initial
trial of such a run, the 25-Hz stimulus (10-s duration) was followed by
a 50-s interstimulus interval (ISI); in the second trial, the 200-Hz
stimulus (10 s in duration) was followed by a 50-s ISI, etc. Twenty to
100 trials were delivered in each run.
Parameters of the 25-Hz stimulus used in the OIS-imaging experiments were as follows: peak-to-peak amplitude, 400 µm; duration, 3-15 s; intertrial interval (ITI), 60 s. The parameters of the 200-Hz stimulus were: peak-to-peak amplitude, 40 µm; duration, 3-15 s; ITI, 60 s. The stimuli were applied by means of a 5-mm-diam, cylindrical Delrin probe, which in every experiment made continuous contact with the skin. In the periods during which no sinusoidal skin displacements were delivered (the intertrial and interrun intervals, respectively), the stimulator probe indented the pad by 500 µm.
2DG imaging
In the 2DG experiments, mechanical skin stimulation was
applied continuously for 0.5-1 h before and for 45 min after pulse intravenous injection of the tracer (300-500 µCi/kg of
14C-2DG). The period of 2DG labeling was
terminated by pentobarbital administration (40 mg/kg iv) followed by
intracardial perfusion with saline and fixative. A tissue block
including SI and SII in both hemispheres was removed, frozen by
immersion in liquid Freon cooled to 50°C, and stored in a
low-temperature freezer (
70°C). Coronal sections were cut in the
coronal plane at 30 µm, placed on coverslips, dehydrated, glued to
cardboard, and exposed to X-ray film (Juliano et al. 1981
,
1983
; Tommerdahl et al. 1993
, 1996
).
Autoradiographs of the distribution of 14C labeling
in cortical sections were viewed with a macroscope fitted with a CCD
camera (Fairchild CCD3000; 488 × 380 element sensor). The camera
generated a standard RS-170 video signal that was digitized using an
imaging board (Datacube; resolution of 768 × 512 × 8 bits
at 30 frames/s). A digital computer and custom-designed image analysis
software allowed conversion of film optical density values to
14C concentrations and calibration, collection, display,
storage, and analysis of imaging data (Tommerdahl 1989;
Tommerdahl et al. 1985
, 1993
, 1996
).
For each autoradiograph, an average 14C concentration value
was determined for each of a continuous series of radially oriented, rectangular bins (bin height 1,000 µm; binwidth 100 µm) spanning the full mediolateral extent of pericoronal cortex. This procedure ("image segmentation") (Tommerdahl 1989;
Tommerdahl et al. 1985
, 1993
, 1996
) yields a series of
14C values, one for each radial bin (segment). Each radial
bin was centered on layer IV to ensure that each average
[14C] value used to form a map of the tangential
distribution of label in pericoronal cortex is based on a data sample
that relates to the locus of maximal input drive in the same way as the
samples derived from all other bins.
An unfolded map of the tangential distribution of
14C-2DG in pericoronal cortex of each subject was
reconstructed. Such a map always included the entire region of
pericoronal cortex expected to receive input from the stimulated skin
site and was generated from the data sampled at relatively low
resolution (20-40 pixels/mm) from 50-100 autoradiographic images. The
data array (the series of average [14C] values generated
by segmenting pericoronal cortex in an autoradiographic image) was
aligned with the arrays obtained from neighboring images by using a
morphological boundary identifiable in all imagesthe point of maximal
curvature of the medial wall of the coronal sulcus (M-COR). Alignment
of the data arrays in this way is a requirement for generation (using
custom-designed graphics software) (Tommerdahl 1989
;
Tommerdahl et al. 1985
) of a two-dimensional
"unfolded" map of the tangential distribution of 2DG labeling
within the cortical region of interest (e.g., Fig.
1). Within such an unfolded map a single
horizontal pixel string corresponds to the mediolateral array of
average [14C] values sampled from a single image.
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OIS imaging
Near-infrared (IR; 833 nm) OIS imaging was carried out
using an oil-filled chamber capped with an optical window
(Tommerdahl and Whitsel 1996; Tommerdahl et al. 1998
,
1999
). Images of the exposed cortical surface were
acquired 200 ms before stimulus onset ("reference" or
"prestimulus" images) and continuously thereafter ("poststimulus" images; at a resolution of 1 image every 0.9-1.4 s) for 15-20 s after stimulus onset. Exposure time was 200 ms.
OIS difference images were generated by subtracting the prestimulus
image from its corresponding poststimulus image. Averaged difference
images typically show regions of both increased absorption of IR light
and decreased absorption of light that have been shown (e.g.,
Grinvald 1985; Grinvald et al. 1991
;
1994
; for review, see Ebner and Chen 1995
; also
Tommerdahl et al. 1998
, 1999
) to be accompanied by
increases and decreases in neuronal activation, respectively.
Difference images of the SI response to stimulation of the same skin
site with 25- and 200-Hz stimulation were generated only from data
obtained in the same experimental run using the interleaved trial
approach described above
this restriction served to control for
temporal changes in cortical "state" unrelated to stimulus
conditions that, if unrecognized, might obscure or modify the optical
response evoked by one or both stimulus frequencies.
The relationship between the optical responses of SI and SII in the
contralateral hemisphere was evaluated by correlation mapping
(Tommerdahl et al. 1998). A correlation map was formed by choosing a reference region within the OIS image and computing the
intensity correlation rij between the
absorbance value of each pixel (i,
j) and the average absorbance within the reference
region over time after stimulus onset. The region in the image selected
as the reference was the region in SI or SII defined by the boxel
(typically, 2 × 2 mm) for which average absorbance underwent the
largest increase during skin stimulation. Each pixel (i,
j) in a correlation map is represented by a correlation
value rij (
1 < r < +1). In other words, each pixel in such a
correlation map shows the value of the correlation between the time
course of the OIS in the reference boxel and the time course of the OIS
measured at that pixel location. The statistical significance of the
computed correlations was evaluated using the standard t-test.
Histological procedures/identification of cytoarchitectural boundaries/reconstruction of the relationships between cytoarchitecture and the 2DG and OIS-imaging observations
2DG IMAGING.
Coronal sections (30-µm thickness) were cut from the block of
cerebral cortex obtained from each subject studied using the 2DG
method; each block included SI and SII in both hemispheres. After
production of an autoradiographic image (on X-ray film) of the
distribution of 14C-2DG within each section, each
section was removed from the coverglass used to maintain it in stable
contact with the X-ray film and was Nissl-stained with cresyl fast
violet (for details, see Tommerdahl et al. 1993, 1996
;
also Juliano et al. 1981
, 1983
). The stained sections
were remounted on slides (serial order was preserved), coverslipped,
and examined microscopically to determine the locations of
cytoarchitectonic boundaries. Cortical cytoarchitecture in the vicinity
of the SI or SII region in which the stimulus evoked above-background
2DG uptake was identified using established criteria (for SI,
Hassler and Muhs-Clement 1964
; Juliano et al.
1981
; McKenna et al. 1981
; for SII,
Burton et al. 1982
; Juliano et al. 1983
). The relationship between 2DG uptake and cortical cytoarchitectonic boundaries in each brain was reconstructed using approaches described in detail in previous publications (Juliano et al. 1981
,
1982
; Tommerdahl et al. 1993
, 1996
).
OIS IMAGING.
In each experiment, a block of tissue that included the region(s)
in the contralateral hemisphere from which OIS responses had been
obtained was removed after intracardial perfusion with saline and
fixative. The block then was postfixed, cryoprotected, and frozen, and
serial sections were cut in the coronal plane (30-µm thickness). The
sections were Nissl-stained with cresyl fast violet. The locations of
cytoarchitectural boundaries in sections at a series of levels within
the territory from which imaging data had been obtained were identified
using the criteria described in the preceding paragraph. For each
subject, the relationship between the OIS-imaging results and cortical
cytoarchitecture was reconstructed using approaches described in detail
in previous papers (Tommerdahl et al. 1998, 1999
).
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RESULTS |
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2DG-imaging experiments
The digitized image of the autoradiograph at the top of Fig. 1 reveals the distribution of 14C-2DG uptake within a single coronal section. The section used to produce this autoradiograph was obtained at an anteroposterior level that included the region of SI in both the right and left hemispheres that receives its input from the skin of the distal forelimb. The stimulus condition used to evoke the localized 14C-2DG uptake apparent in this image (dark regions indicate regions of high 14C-2DG uptake) was uninterrupted 25-Hz stimulation of the central pad on the left forepaw and, simultaneously, continuous 200-Hz stimulation of the central pad on the right forepaw.
A distribution of 14C-2DG uptake in SI similar to
that in the image at the top of Fig. 1 was obtained in all
three subjects studied in the same way. Specifically, a prominent
column-shaped patch of elevated uptake extending continuously between
layers II and V was present in the superficial part of the medial bank of the coronal sulcus (M-COR) in the right hemispherethe location of
this patch of tracer accumulation in the right hemisphere of the image
shown in Fig. 1 (and in the hemisphere contralateral to the 25-Hz
stimulus in the other 2 subjects
not shown) occupies a territory in SI
demonstrated by previous receptive-field mapping studies to receive its
principal afferent input from the skin of the contralateral central pad
(e.g., McKenna et al. 1981
). In contrast, no region(s)
within the topographically corresponding region of SI in the hemisphere
contralateral to the central pad that received 200-Hz stimulation
(e.g., left hemisphere in the image at top of Fig. 1)
exhibited above-background 14C-2DG uptake in any
of the three subjects.
Immediately below the digitized image at the top of Fig. 1 are two unfolded maps, each showing the tangential distribution of labeling (in terms of [14C] values; depicted in grayscale) within the pericoronal cortex of one hemisphere. Both of the unfolded maps in Fig. 1 were generated from the data (average [14C] values at each of a series of locations in each of a large number of images; 110 images were used for the map on the right, 85 for the map on the left) obtained from coronal sections separated by no more than 150 µm.
Inspection of the unfolded 2DG maps in Fig. 1 confirms, for the same
subject that provided the image of the single section shown at the
top of the same figure, that the distribution of 14C-2DG uptake in the hemisphere contralateral to
the 25-Hz stimulus (map at right of Fig. 1) includes a
prominent region of above-background tracer accumulation where SI
cortex folds to form the medial bank of the coronal sulcus (M-COR), and
that an absence of above-background uptake at all SI
locations contralateral to the skin site that received 200-Hz
stimulation (map at left of Fig. 1). In addition, the two
plots in Fig. 1, bottom, allow direct comparison of the tangential distribution of 14C-2DG uptake in SI
in the two hemispheresmore specifically, these two plots show how
average 14C-2DG uptake (average
[14C]) varies as a function of increasing
radial distance (binwidth = 7 µm) from a reference point common
to both maps. The reference point for the 14C
concentration values plotted with the thin line is the mediolateral position at which 14C-2DG uptake is
maximal in the map of SI contralateral to the 25-Hz central-pad
stimulus
this position is designated as 0.0 on the x axis
and is identified by the × located in the inset below the
unfolded map on the right. Similarly, the mediolateral location of the topographically corresponding point in the unfolded map
of SI contralateral to the 200-Hz stimulus (identified by superimposing
the unfolded maps for left and right pericoronal cortex) is also at the
0.0 point on the x axis, and average
14C concentration value in this unfolded map is
plotted (heavy line) as a function of increasing radial distance from
the reference point (point × in the inset diagram of the
unfolded map shown on the left immediately above
the bottom panel in Fig. 1).
Briefly summarized, the [14C] versus distance
plots in Fig. 1, bottom, show that the spatial distribution
of 14C-2DG uptake in SI of the hemisphere
contralateral to the 25-Hz stimulus (thin line) included a prominent
and spatially localized region of elevated uptake (~1.7 mm in
diameter, located near to the top of the medial bank of the coronal
sulcus). In contrast, at all locations in SI of the hemisphere
contralateral to the 200-Hz stimulus (plot with heavy line Fig. 1,
bottom) uptake did not differ substantially from background.
Background 14C-2DG uptake was estimated as the
average [14C ] observed at locations >3 mm in
all directions from the point of maximal uptake (point 0,0)for the
data shown in Fig. 1, this approach to estimating background yields
essentially the same result for both hemispheres.
A somewhat different design was used in two additional subjects studied
using the 2DG mapping method. Specifically, in these experiments a
200-Hz stimulus was delivered to the central pad on the right forelimb;
no stimulus was delivered to the left forelimb; and a plane of cortical
section was used that included the central-pad representational
territory in both SI and in SII of the hemisphere contralateral to the skin site that received 200-Hz stimulation. It was
anticipated that this design would provide data bearing on a
possibility that cannot be rejected on the basis of the data shown in
Fig. 1the lack of a region of elevated 14C-2DG
uptake in SI in the hemisphere contralateral to 200-Hz stimulation might have been due to a failure to deliver an effective 200-Hz skin stimulus.
Figure 2 shows a representative image (at the top) showing the distribution of 14C-2DG in a section from one of the two subjects studied using the design described in the preceding paragraph. Note the prominent column-shaped profile of above-background uptake in the contralateral SII and the absence of above-background label in SI in the same hemisphere. The importance of this outcome is that it not only demonstrates that the 200-Hz stimulus evoked significant afferent drive that activated SII in the contralateral hemisphere, but it reveals that the same 200-Hz stimulus did not cause significant activation of the contralateral SI. In all subjects studied with the 2DG method (n = 5; 3 using the design illustrated in Fig. 1, 2 using the design shown in Fig. 2), 200-Hz stimulation of the central pad evoked above-background labeling in SII in the hemisphere contralateral to the stimulated skin site but failed to evoked appreciable uptake in the contralateral SI.
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OIS-imaging experiments
Figure 3 shows OIS imaging results
obtained from three subjectsthe images obtained from the same subject
occupy a single row. In all three subjects, the 25-Hz contralateral
central-pad stimulus (Fig. 3, left) evoked a prominent
increase in absorbance that was most prominent in areas 3b and 1 but
also involved area 3a. The fact that the region exhibiting an increase
in absorbance evoked by 25-Hz stimulation appears to be more spatially
extensive in one subject (subject 2) than the region in
which absorbance was increased in the other two subjects is interpreted
as attributable mainly to the fact that in subject 2 the
entire responding area occupies exposed cortex, whereas in both of the
other subjects, a significant portion of the responding cortex occupied
regions buried in the medial wall of the coronal sulcus. This
interpretation is consistent with the demonstrations by previous
receptive-field mapping studies that in some but not all cats, a
portion of the SI central-pad representational area can lie within
cortex buried in the medial bank of the coronal sulcus (McKenna
et al. 1981
).
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In striking contrast to the prominent SI optical responses obtained in subjects with 25-Hz stimulation, stimulation of the same central-pad site with the 200-Hz stimulus failed to evoke a discernable change in absorbance in either area 3b or area 1 (compare Fig. 3, middle with left). Instead, in the three subjects whose data are shown in Fig. 3, 200-Hz stimulation was accompanied only by an extremely weak absorbance increase in area 3a (e.g., the response in area 3a to 200-Hz stimulation is most apparent in subject 2 in Fig. 3).
Figure 4 shows results obtained in two OIS-imaging experiments in which the central-pad representational area in both SI and SII in the contralateral hemisphere were imaged simultaneously in response to interleaved trials of 25- and 200-Hz stimulation. Fig. 4, top, shows, for both subjects, the responses of the contralateral SI and SII 5 s after onset of a 25-Hz stimulus. The images in Fig. 4, middle, show the responses obtained from SI and SII of the same two subjects 5 s after onset of a 200-Hz stimulus to the same central-pad site. Comparison of the images in the top two rows in Fig. 4 makes it obvious that although SI in both subjects (SI is located at the top right of the field imaged in both experiments; SII is located at the left of each field) underwent a prominent increase in absorbance in response to the 25-Hz central-pad stimulus condition, SI did not. More specifically, subject 1 exhibited little or no increase in SI absorbance in response to same-site 200-Hz stimulation (middle left), and although a small increase in SI absorbance did occur in subject 2 (middle right), it does not approach the magnitude of the increase in absorbance evoked in SI of the same subject by same-site 25-Hz stimulation.
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Although Fig. 4 makes it apparent that SII underwent a large increase
in absorbance in response to both the 25- and 200-Hz stimuli, it is
interesting that the region in SII that responded with an absorbance
increase is not the same for the two stimulus frequencies. In both
subjects whose data are seen in Fig. 4, the SII region that responded
to 200-Hz stimulation only partially overlaps the region that responded
to 25-Hz stimulationthe territory that responds to 200 Hz is located
slightly more posterior than the one that responds to 25-Hz
stimulation. This difference in the SII locus of the responses to 25- and 200-Hz stimulation is most apparent when (see Fig. 5,
top) the difference images obtained from each subject under
the two stimulus conditions are thresholded and superimposed (in the
thresholded images, gray = the SI and SII areas responding to 200 Hz and black = SI and SII areas responding to 25 Hz).
Because the OIS images in Figs. 3 and 4 only show the responses of SI and SII at single time (5 s) after stimulus onset, the time course of the SI and SII responses to each stimulus frequency was evaluated to determine if, and to what extent, the responses modify with time after stimulus onset. The following three-step procedure was used. First, the 2 × 2 mm boxel within SI that exhibited the largest increase in average absorbance at 5 s after onset of 25-Hz stimulation and the 2 × 2mm boxel within SII that exhibited the maximal absorbance increase to the same stimulus condition were identified. Second, the average absorbance value within the same SI and SII boxels were determined for each difference image acquired after the onset of each stimulus frequency. And third, average absorbance in each boxel was plotted as a function of time after stimulus onset.
The graphs in Fig. 5 (left: subject 1; right: subject 2) show, for the same two subjects whose data are shown in Fig. 4, the time course of the absorbance change within the abovementioned SI and SII boxels during 25-Hz stimulation (plotted using heavy lines) and during 200-Hz stimulation of the central pad (plotted using thin lines). For subject 1 the duration of both the 25- and 200-Hz stimuli was 10 s; it was 20 s for subject 2. The graphs in Fig. 5 clearly reveal that in each subject 25-Hz stimulation evoked an increase in absorbance in both the SI and SII boxels and that the increase in absorbance evoked by 25-Hz stimulation in both the SI and SII boxels developed relatively rapidly after stimulus onset. Moreover, they show that in the SI and SII boxels in both subjects absorbance is near-maximal within 3-5 s of onset of 25-Hz stimulation and declines to ~65-80% of its maximal value with continuing stimulation. Two hundred-Hz stimulation, like 25-Hz stimulation, evoked in both subjects a prominent and rapidly developing increase in absorbance in the SII boxel, but unlike 25-Hz stimulation, elicited only a weak and slow-to-develop increase in absorbance in the SI boxel in subject 2 and a biphasic change in absorbance (a weak increase at 1 s after stimulus onset, followed by a frank decrease) in the SI boxel in subject 1.
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Figure 6 shows that very similar findings obtained from the contralateral SI in three additional subjects studied with the OIS-imaging method (see legend to Fig. 6 for details). In general, the findings obtained from the five subjects whose data are shown in Figs. 5 and 6 indicate the considerable across-subject consistency of the prominent, but very different, optical responses of the contralateral SI to same-site 25- and 200-Hz stimulation.
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The next and final approach we used to analyze the OIS-imaging data was
correlation mapping. More specifically, the method of correlation
mapping was used 1) to obtain an outcome (a correlation map)
for each stimulus condition that provides an objective measure (a
correlation value) of the association between the time course of the
change in absorbance within the region of maximal activity and the time
course of change in absorbance at each pixel location outside the
maximally activated region, 2) to objectively specify the
outcome of functional interactions between cortical regions in terms of
the value and sign of the measured correlation, and 3) to
assess the statistical significance of the correlation measured at each
cortical site (see Tommerdahl et al. 1998).
Maps showing the correlation between the time course of the change in
absorbance at each pixel location with those that occurred within the
maximally activated boxel in SII were generated for the two subjects in
whom SI and SII in the same hemisphere were imaged simultaneously (see
Figs. 4 and 5)for each of these subjects, a correlation map was
generated using the data obtained under the 25-Hz stimulus condition
and also using the data obtained under the 200-Hz condition. Figure
7 shows the correlation maps generated
from the data of subject 1 obtained under 25-Hz stimulation (top) and under 200-Hz stimulation (bottom).
|
Inspection of the correlation map generated for the 25-Hz condition (Fig. 7, top) reveals that under this condition the activities in extensive areas (indicated in red) in both SI and SII in the contralateral hemisphere are highly positively correlated with the increase in absorbance that occurred in the maximally activated SII boxel. In contrast, the correlation map generated for the 200-Hz condition (Fig. 7, bottom) shows that under this condition the activity within an extensive region of SII and the fields that border it (e.g., area SIV) is correlated positively (shown in red) with the increase in absorbance that occurs in the maximally activated SII boxel, whereas the activity in much of SI is highly and significantly anticorrelated (indicated in blue) with the time course of the activity in the SII boxel. The correlation maps generated in the same way from the other subject (subject 2; see Fig. 4) exhibited characteristics similar to those of the maps in Fig. 7.
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DISCUSSION |
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Effects of high-frequency skin stimulation on the contralateral SI
The 2DG- and the OIS-imaging observations from cat SI closely
parallel the results obtained recently in a study of SI in squirrel monkeys (Tommerdahl et al. 1999). That study showed that
a 1- to 5-s 25-Hz skin stimulus evokes a prominent, well-maintained absorbance increase in the topographically appropriate locus in contralateral area 3b and/or area 1, whereas delivery of 200-Hz stimulation to the same skin site results in only a weak and transient increase in absorbance at the same SI locus. In addition, it was shown
that as stimulus duration increased, the difference between the
squirrel monkey SI optical responses evoked by 25- versus 200-Hz
stimulation becomes progressively more distinct. In particular, with
25-Hz stimulation, a large absorbance increase developed rapidly and
was relatively well maintained as long as the stimulus was continued.
In contrast, with 200-Hz stimulation, an early, weak increase in
absorbance occurred, but within 3-5 s of stimulus onset, it was
replaced by a prominent and spatially extensive region of decreased
absorbance that persisted until stimulation was discontinued
(Tommerdahl et al. 1999
).
Neither the OIS- nor the 2DG-imaging results reported in this study,
nor the findings reported by Tommerdahl et al. (1999) in
squirrel monkey SI, are easily accommodated with one component of the
long-held view (Hyvarinen et al. 1968
;
Mountcastle et al. 1967
, 1969
, 1990
;
Talbot et al. 1968
; for review, see Mountcastle 1984
) that dual neural mechanisms in SI cortex underlie the
capacities to detect and discriminate frequency of vibrotactile
stimulation. Specifically, the data appear at conflict with the idea
that a distinct class of SI neurons signals by either a periodicity or mean rate code, the higher stimulus frequencies (>60 Hz) at which humans experience vibration.
It should be noted that a number of findings in the published
literature, similar to the observations reported in this paper, also
are not easily accommodated with the idea that it is the PC-type SI
neurons that encode the frequency of skin stimulation over the range
which humans experience as vibration. First, Mountcastle et al.
(1969) demonstrated in their elegant initial study of the cortical mechanisms in flutter-vibration that neither the overall mean
firing rate nor any periodic ordering of the spikes discharged by
PC-type SI neurons provides a discriminable signal of frequency at
stimulus frequencies between 100 and 200 Hz. Second, Lebedev et
al. (1994)
reported that during the delivery of 127-Hz
stimulation to the contralateral palm the mean firing rate (MFR) of SI
neurons in conscious behaving monkeys is significantly lower than the firing rates evoked at 27 and 57 Hz
a finding that led Lebedev et al. (1994)
to conclude that the "decrease in MFR of
neurons with cutaneous RFs at 127 Hz may be due to inhibitory
mechanisms dependent on stimulus frequency." Third, in cats,
high-frequency (
200 Hz) skin stimuli have been reported to activate
SII neurons far more effectively than SI neurons (McIntyre et
al. 1967
; Rowe et al. 1985
). And fourth,
Pertovaara and Hamalainen (1981)
interpreted their human
psychophysical evidence to indicate that long-duration high-frequency
skin stimuli inhibit the detection of low-frequency stimuli.
Although it is true that the preceding observations, either individually or collectively, do not permit conclusions about the detailed nature of the neuronal processes triggered in SI cortex by high-frequency skin stimulation, all appear generally consistent with the possibilities that the effects of 200-Hz skin stimulation on SI 1) are more complex than would be anticipated if the SI mechanisms subserving flutter-vibration consisted solely of dual, independent neuron populations, each devoted exclusively to processing the afferent drive arising in one class (either the RA- or PC-type) of skin mechanoreceptors and 2) involve a potent, spatially widespread, and generalized inhibitory influence on SI neurons. The latter possibility is viewed as fully consistent with the observation that SI and SII activities are highly negatively correlated (see Fig. 7) under the condition of 200-Hz skin stimulation.
Interdependencies between SI and SII
The available literature indicates that SII derives the major
component of its input from SI in the same hemisphere in macaque monkeys (Pons et al. 1987) but receives its principal
input from the thalamus in cats (Alloway et al. 1988
;
Bennett et al. 1980
; Ferrington and Rowe
1980
; Fisher et al. 1983
; Herron and
Dykes 1986
). Although this prominent species difference in SII
afferent connectivity has been proposed to indicate that in monkey SII occupies a higher position in the somatosensory information processing hierarchy than in cat (Pons et al. 1987
), others have
warned that "these are basically descriptive schemes of connections
that do not illuminate what features of somesthesis are selectively
projected" and that "they also tend to ignore potential
interdependence between SI and SII" (Burton and Sinclair
1991
).
The OIS observations obtained in the present study by simultaneously
imaging the contralateral SI and SII in cats during 200-Hz stimulation
of the central pad (Figs. 4, 5, and 7) revealed that the time course of
the optical response (increasing absorbance) evoked in SII is strongly
and significantly negatively correlated with the time course of the
optical signal in the region of the topographically appropriate region
of SI. A plausible (but not necessarily correct) explanation for this
outcome is that the activity evoked in SII exerts an inhibitory
influence on SI via the extensive corticocortical connections known
(Burton et al. 1995) to link topographically
corresponding regions in the two areas. At the same time, the
observations obtained during 25-Hz stimulation suggest (see Figs. 4, 5,
and 7) that SI and SII in cat may function relatively more
independently under this stimulus condition.
It is important to emphasize that the data presented in this paper
cannot be used to evaluate any particular model of information flow
(e.g., the serial vs. parallel models of information flow). These
models address the sources of the information that reaches SI and SII,
whereas the data presented in this paper address a completely different
issuewhether, and to what extent, the responses of SI and SII in the
same hemispheres are independent.
The data presented show that nonnoxious mechanical skin stimulation (both low and high frequency) evoke afferent activity that is conveyed via central somatosensory paths to both SI and SII in the contralateral hemisphere and raise the possibility that unlike the activity evoked by cutaneous flutter, the vigorous SII activity generated by high-frequency skin stimulation (vibration) may depress (perhaps via inhibitory processes mediated by cortico-cortical connections) the response of SI to ongoing skin stimulation. Thus one possible interpretation is that SII activity levels mediate SI response, particularly when these activity levels have been evoked by vibratory stimuli. The findings appear to require the conclusion that, at least in cat the degree to which SI and SII in the contralateral hemisphere contribute to the somatosensory cortical response to skin stimulation is frequency-dependent with SII making a progressively greater and SI a progressively lesser contribution to the response of the contralateral hemisphere as stimulus frequency is increased >25 Hz.
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ACKNOWLEDGMENTS |
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The authors acknowledge the expert technical support of C. Wong.
M. Tommerdahl was supported in part by National Institute of Neurological Disorders and Stroke (NINDS) R29 Grant NS-32358. The experiments were funded by NINDS RO1 Grant NS-34979 (B. L. Whitsel).
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FOOTNOTES |
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Address for reprint requests: M. Tommerdahl, Dept. of Biomedical Engineering, University of North Carolina, CB# 7575, Chapel Hill, NC 27599.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 16 February 1999; accepted in final form 27 May 1999.
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REFERENCES |
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