Department of Neurology, Heinrich-Heine-University, D-40225 Düsseldorf, Germany
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ABSTRACT |
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Ploner, Markus, Frank Schmitz, Hans-Joachim Freund, and Alfons Schnitzler. Differential Organization of Touch and Pain in Human Primary Somatosensory Cortex. J. Neurophysiol. 83: 1770-1776, 2000. Processing of tactile stimuli within somatosensory cortices has been shown to be complex and hierarchically organized. However, the precise organization of nociceptive processing within these cortices has remained largely unknown. We used whole-head magnetoencephalography to directly compare cortical responses to stimulation of tactile and nociceptive afferents of the dorsum of the hand in humans. Within the primary somatosensory cortex (SI), nociceptive stimuli activated a single source whereas tactile stimuli activated two sequentially peaking sources. Along the postcentral gyrus, the nociceptive SI source was located 10 mm more medially than the early tactile SI response arising from cytoarchitectonical area 3b and corresponded spatially to the later tactile SI response. Considering a mediolateral location difference between the hand representations of cytoarchitectonical areas 3b and 1, the present results suggest generation of the single nociceptive response in area 1, whereas tactile stimuli activate sequentially peaking sources in areas 3b and 1. Thus nociceptive processing apparently does not share the complex and hierarchical organization of tactile processing subserving elaborated sensory capacities. This difference in the organization of both modalities may reflect that pain perception rather requires reactions to and avoidance of harmful stimuli than sophisticated sensory capacities.
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INTRODUCTION |
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The primary somatosensory cortex (SI) participates
in central processing of both tactile and nociceptive stimuli (for
reviews see Kaas 1990; Kenshalo and Willis
1991
). However, SI is not a homogeneous area but consists of
four cytoarchitectonically distinct fields arranged from rostral to
caudal and referred to as areas 3a, 3b, 1, and 2 (Brodmann
1909
; Vogt and Vogt 1919
). These areas each
contain a separate body representation (Kaas et al.
1979
) characterized by a distinct connectivity (Burton
and Fabri 1995
; Felleman and Van Essen 1991
;
Jones 1984
, 1986
), submodality distribution (Iwamura et al. 1993
; Kaas et al. 1979
;
Powell and Mountcastle 1959
), and receptive field
configuration (Hyvärinen and Poranen 1978
;
Iwamura et al. 1993
; Kaas et al. 1979
).
Cutaneous information is predominantly processed in areas 3b and 1 whereas areas 3a and 2 mainly receive information from the deep body
tissues (Hyvärinen and Poranen 1978;
Iwamura et al. 1993
; Powell and Mountcastle
1959
). The cutaneous fields areas 3b and 1 are connected with
area 2, the posterior parietal cortex, and the secondary somatosensory
cortex (Burton and Fabri 1995
; Burton et al.
1995
; Jones et al. 1978
). Anatomic
(Burton and Fabri 1995
; Felleman and Van Essen
1991
; Jones 1986
) and physiologic studies
(Garraghty et al. 1990
; Hyvärinen and
Poranen 1978
; Iwamura et al. 1993
; Kaas
et al. 1979
; Pons et al. 1992
) indicate a
partially hierarchical organization of these areas with area 3b
representing the first cortical stage of tactile processing (for review
see Iwamura 1998
).
Accordingly, neurophysiological recordings in monkeys and humans have
revealed that the earliest cortical components of somatosensory evoked
potentials and fields originate from area 3b located in the rostral
bank of the postcentral gyrus (Allison et al. 1989a; McCarthy et al. 1991
; Wood et al. 1985
,
1988
). Subsequent responses are generated in the caudally
adjoining area 1 and later in the posterior parietal cortex and
SII (Allison et al. 1989a
,b
; Forss et al.
1994
; Hari et al. 1993
; McCarthy et al.
1991
; Wood et al. 1985
, 1988
).
By contrast, a recent study in humans demonstrated simultaneous
activation of SI and SII to nociceptive stimuli suggesting a parallel
activation pattern (Ploner et al. 1999). However, within SI, the organization of nociceptive processing has remained largely unknown. Thus it is unclear whether the complex and hierarchical organization of tactile processing subserving elaborated sensory capacities also applies to human pain processing. We therefore used
whole-head magnetoencephalography (MEG) to record cortical responses to
tactile and nociceptive stimuli in healthy human subjects. By directly
comparing cortical responses to both stimuli in the same subjects we
investigated whether nociceptive processing shares the organization of
tactile processing within SI.
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METHODS |
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Six healthy male right-handed volunteers with a mean age of 33 yr (range, 28-38 yr) participated in the experiment. All subjects were experienced in pain experiments and gave their informed consent before participation. The study was approved by the local ethics committee.
Stimulation
Tactile and nociceptive afferents of the hands were stimulated
by using electrical sensory nerve and cutaneous laser stimulation, respectively. For the nociceptive stimulations data of three subjects from our previous study (Ploner et al. 1999) were included.
In separate runs, 40 selective nociceptive cutaneous laser stimuli
(Bromm and Treede 1984
) were delivered to the dorsum of each hand in the territory of the superficial branch of the radial nerve. Right and left hand were stimulated in subsequent runs. The
laser device was a Tm:YAG-laser (Baasel Lasertech) with a wavelength of
2000 nm, a pulse duration of 1 ms, and a spot diameter of 6 mm.
Interstimulus intervals were randomly varied between 10 and 14 s
and stimulation site was slightly changed after each stimulus to avoid
tissue damage and sensitization and habituation effects. Stimulation
intensity was adjusted to twofold pain threshold intensity, i.e.,
600-700 mJ pulse energy. In each individual, laser stimuli elicited
clearly painful "pinprick-like" but no tactile sensations.
Tactile afferents were stimulated with 0.3 ms constant voltage pulses delivered to the superficial branch of the radial nerve just proximal to the wrist. At least 150 stimuli each were alternately delivered to both sides at random interstimulus intervals between 2 and 3 s. Stimulus intensity was adjusted to twofold detection threshold intensity, i.e., 40-60 V, thus inducing clear and consistent nonpainful sensations. An electrical stimulus was chosen because its duration closely matches that of the laser stimulus. Moreover, electrical stimuli yield highly synchronized volleys and therefore evoke well-defined and well-studied cortical responses with signal-to-noise ratio superior to natural tactile stimuli. In a control experiment, we verified that locations of reponses to electrical stimuli match those to natural tactile stimuli: In 3 subjects, 150 natural tactile stimuli were delivered to the dorsum of each hand with a pneumatically driven aluminum cylinder of 2 mm diam and a skin contact duration of 600 ms.
Data acquisition and analysis
Cortical activity was recorded with a Neuromag-122 whole-head
neuromagnetometer (Ahonen et al. 1993) in a magnetically
shielded room. The helmet-shaped sensor array contains 122 planar SQUID gradiometers which detect the largest signals just above the local cortical current sources. Signals were recorded with a 0.03 Hz high-pass filter and digitally low-pass filtered at 120 Hz. Cortical responses were averaged time-locked to stimulus application. Vertical electrooculogram was used to reject epochs contaminated with blink artifacts. Analysis of evoked responses was focused on an epoch comprising 100 ms prestimulus baseline and 300 ms after stimulation. Sources of responses were modeled as equivalent current dipoles identified during clearly dipolar field patterns. Only sources accounting for more than 85% of the local field variance (goodness of
fit) and with 95% confidence limits of source localization <10 mm
were accepted. Dipole location, orientation, and strength were
calculated within a spherical conductor model of each subject's head
determined from the individual magnetic resonance images (MRI) acquired
on a 1.5 T Siemens-Magnetom. Dipoles were introduced into a
spatio-temporal source model where locations and orientations were
fixed and source strengths were allowed to vary over time to provide
the best fit for the recorded data (for further details concerning data
acquisition and analysis see Hämäläinen et al.
1993
). Resulting source strengths as a function of time were used for latency determination.
Based on fiducial point markers, MRI and MEG coordinate systems were
aligned and sources were superposed on the individual MRI scans. In
each individual, distances along the three axes of the Talairach
coordinate system (Talairach and Tournoux 1988) were
calculated between locations of tactile and nociceptive responses. In
addition, source locations were calculated in standardized Talairach coordinates.
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RESULTS |
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In all subjects, stimulation of tactile afferents elicited clear and consistent nonpainful sensations. Conversely, nociceptive stimulation evoked at least moderately painful but no tactile sensations.
In all subjects, the well-known early 20-ms and 30-ms responses to tactile stimulation were explained by a single dipole, fitted around 30 ms, in the contralateral postcentral gyrus corresponding to the hand area of SI. In 9 of 12 hemispheres (5 left and 4 right), an additional subsequently peaking source in the contralateral SI hand area located more medially was necessary to explain the recorded signals. These early SI responses were followed by activity originating from the contralateral posterior parietal cortex in three recordings, and in all recordings, from the upper banks of the Sylvian fissures, bilaterally, corresponding to SII. By contrast, nociceptive stimuli nearly simultaneously activated a single source in the contralateral postcentral gyrus (SI) and bilateral sources in the upper banks of the Sylvian fissures (SII). No nociceptive responses were recorded from the posterior parietal cortex. Latencies and mean standardized Talairach coordinates of nociceptive and tactile responses are given in Table 1.
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Figure 1 compares magnetic field patterns, source locations, and source strength waveforms to both stimuli in a single subject. The figure illustrates that, along the postcentral gyrus, the nociceptive SI source was located more medially than the tactile 30-ms response. However, the location of the nociceptive source corresponded well to the later peaking tactile SI source. In addition, tactile stimuli later elicited a response arising from the posterior parietal cortex, whereas no corresponding activity was recorded to nociceptive stimuli.
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Figure 2 shows locations of later peaking tactile SI responses (Fig. 2A) and nociceptive sources (Fig. 2B) in SI with respect to the tactile 30-ms response (coordinate center) in axial and coronal planes in all subjects. In each individual, both responses were located more medially and caudally than the tactile 30-ms source. In no subject was there any overlap of 95% confidence limits of source localization with the 30-ms response. The insert in the middle row of the figure demonstrates that the mean relative location of the later peaking tactile SI source and the nociceptive SI source were nearly coinciding. The control experiment revealed that locations of early responses to natural tactile stimuli closely match locations of 30-ms responses to sensory nerve stimuli (mean location difference along x, y and z axis; 0 mm, 0 mm, and 2 mm).
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Figure 3 demonstrates that there was no systematical difference between locations of tactile and nociceptive sources in SII.
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DISCUSSION |
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In this study, we compared cortical responses to tactile
and nociceptive stimuli in human somatosensory cortices. Within SI, our
results reveal a fundamental difference in the representation of both
modalities: Stimulation of tactile afferents activated two sequentially
peaking sources within SI, whereas nociceptive stimuli merely evoked a
single SI response. Along the postcentral gyrus, this single
nociceptive source was significantly more medially located than the
early tactile 30-ms response and corresponded spatially to the later
peaking tactile source. These results expand previous findings
indicating distinct temporal activation patterns of SI and SII in
nociceptive and tactile processing (Ploner et al. 1999).
Intra- and extracranial recordings in monkeys (McCarthy et al.
1991) and humans (Allison et al. 1989a
;
Wood et al. 1985
) revealed generation of the early 20-ms
and 30-ms components of somatosensory evoked potentials and fields in
cytoarchitectonical area 3b. Accordingly, in this study, 30-ms SI
responses to tactile stimuli most likely arise from area 3b in the
rostral bank of the postcentral gyrus. By contrast, the more medial
location of both the nociceptive and the later peaking tactile source
suggests generation of these responses in cytoarchitectonical area 1. A
mean mediolateral location difference to the 30-ms response of 10 mm
corresponds to a mediolateral location difference between the hand
representations of areas 1 and 3b as revealed by intracranial
recordings (Allison et al. 1989a
; McCarthy et al.
1991
; Wood et al. 1988
), and anatomic
(Jones et al. 1982
), metabolic labeling (Juliano
and Whitsel 1985
), and functional neuroimaging studies
(Burton et al. 1997
). In humans, this mediolateral
distance between responses attributed to areas 1 and 3b amounts to
~10 mm (Allison et al. 1989a
; Burton et al. 1997
; Wood et al. 1988
) and thus agrees well
with our findings.
Macrostructurally, in humans, area 1 has been shown to comprise the
crown of the postcentral gyrus and the superficial parts of its rostral
and caudal banks (Geyer et al. 1997, 1999
; White et al. 1997
). Consequently, because MEG does not detect
radially oriented currents (Hämäläinen et al.
1993
), recorded activity might predominantly originate from the
fissural parts and less from the convexial parts of area 1. Conversely,
a mainly radial orientation of convexial area 1 sources and the
predominance of more consistently activated 3b sources (Allison
et al. 1989a
; Wood et al. 1985
, 1988
) may
account for the partial failure to detect area 1 responses in MEG.
Furthermore, in previous studies using median nerve stimuli, frequent
activation of posterior parietal cortex might have complicated
identification of area 1 sources (Forss et al. 1994
).
However, in the posterior parietal cortex, most somesthetic neurons
respond to complex activations of deep receptors related to exploratory
movements (for review see Hyvärinen 1982
).
Consequently, in this study, stimulation of a cutaneous nerve branch
supplying the dorsum of the hand might have accounted for less
intensive activation of the posterior parietal cortex thus facilitating
detection of area 1 sources.
Generation of nociceptive SI responses in cytoarchitectonical area 1 is
supported by results from experimental animal studies: Single neuron
recordings in monkeys revealed location of most nociceptive SI neurons
at the rostral and caudal borders of area 1 (Chudler et al.
1990; Kenshalo and Isensee 1983
). In addition, positron emission tomography studies in humans directly comparing locations of SI responses to nociceptive and tactile stimuli
(Coghill et al. 1994
; Iadarola et al.
1998
) showed a corresponding slight but insignificant
mediolateral location difference between activation foci. By contrast,
using intrinsic optical imaging, a recent study in monkeys showed
pain-associated activations in area 3a whereas neuronal activity in
areas 1 and 3b was suppressed by painful stimuli (Tommerdahl et
al. 1998
). However, in this study, temporal dimensions of
stimulations and responses were in the range of seconds and thus differ
from the brief stimuli and responses recorded in our study which
probably reflect distinct neural mechanisms. Furthermore, in this
(Tommerdahl et al. 1998
) and the aforementioned studies
(Coghill et al. 1994
; Iadarola et al.
1998
), as a result of different stimulus characteristics and
recording techniques, responses were most likely mainly mediated by
slowly conducting C fibers whereas in the present study exclusively
early A-
fiber mediated responses were analyzed.
Locations of SII activations to nociceptive and tactile stimuli did not differ systematically. However, considering the small extent of SII and the complex folding of cortex buried in the Sylvian fissure, the possibility remains that spatial resolution of MEG might be insufficient to detect a consistent macrostructurally definable location difference.
In tactile processing, anatomic and physiologic investigations have
revealed a partially hierarchical organization of somatosensory cortices with area 3b representing the first cortical stage of a
processing cascade comprising area 1, the posterior parietal cortex and
SII (for review see Iwamura 1998). Our result of
sequentially peaking sources in area 3b, area 1, the posterior parietal
cortex, and SII is likely to reflect this organizational mode. By
contrast, generation of nociceptive SI responses merely in area 1 is in conflict with this processing hierarchy and thus complements previous findings indicating direct thalamic access of nociceptive information to SII (Ploner et al. 1999
).
Taken together, nociceptive processing apparently does not share the
elaborated and hierarchical organization of tactile processing which
probably evolutionary evolved in parallel with an improvement in
sensory capacities. Instead, direct projections from area 1 (Burton et al. 1995; Jones et al. 1978
;
Stepniewska et al. 1993
) and SII to the primary motor
cortex (Friedman et al. 1986
) and from SII via the
insula to the temporal lobe limbic structures (Friedman et al.
1986
; Shi and Cassell 1998
) would provide an appropriate anatomic substrate for fast and effective integration of
nociceptive information into motor and memory processes.
Teleologically, this organization appears reasonable as, in pain
perception, effective reactions to and future avoidance of harmful
stimuli are obviously more important than object identification or
manipulation, the more so as almost every painful stimulus is coupled
with activation of tactile pathways.
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ACKNOWLEDGMENTS |
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We thank C. J. Ploner for helpful comments on the manuscript and J. Gross for technical support.
This study was supported by the Ute-Huneke-Stiftung, the Deutsche Forschungsgemeinschaft (SFB 194), and the Volkswagenstiftung.
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FOOTNOTES |
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Address for reprint requests: A. Schnitzler, Dept. of Neurology, Heinrich-Heine-University, Moorenstrasse 5, D-40225 Düsseldorf, Germany.
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 9 October 1999; accepted in final form 9 December 1999.
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REFERENCES |
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