1Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139; 2Massachusetts General Hospital Nuclear Magnetic Resonance Center, Charlestown 02129; and 3Department of Psychology, Boston University, Boston, Massachusetts 02215
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ABSTRACT |
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Moore, Christopher I., Chantal E. Stern, Suzanne Corkin, Bruce Fischl, Annette C. Gray, Bruce R. Rosen, and Anders M. Dale. Segregation of Somatosensory Activation in the Human Rolandic Cortex Using fMRI. J. Neurophysiol. 84: 558-569, 2000. The segregation of sensory information into distinct cortical areas is an important organizational feature of mammalian sensory systems. Here, we provide functional magnetic resonance imaging (fMRI) evidence for the functional delineation of somatosensory representations in the human central sulcus region. Data were collected with a 3-Tesla scanner during two stimulation protocols, a punctate tactile condition without a kinesthetic/motor component, and a kinesthetic/motor condition without a punctate tactile component. With three-dimensional (3-D) anatomical reconstruction techniques, we analyzed data in individual subjects, using the pattern of activation and the anatomical position of specific cortical areas to guide the analysis. As a complimentary analysis, we used a brain averaging technique that emphasized the similarity of cortical features in the morphing of individual subjects and thereby minimized the distortion of the location of cortical activation sites across individuals. A primary finding of this study was differential activation of the cortex on the fundus of the central sulcus, the position of area 3a, during the two tasks. Punctate tactile stimulation of the palm, administered at 3 Hz with a 5.88log10.mg von Frey filament, activated discrete regions within the precentral (PreCG) and postcentral (PoCG) gyri, corresponding to areas 6, 3b, 1, and 2, but did not activate area 3a. Conversely, kinesthetic/motor stimulation, 3-Hz flexion and extension of the digits, activated area 3a, the PreCG (areas 6 and 4), and the PoCG (areas 3b, 1, and 2). These activation patterns were observed in individual subjects and in the averaged data, providing strong evidence for the existence of a distinct representation within area 3a in humans. The percentage signal changes in the PreCG and PoCG regions activated by tactile stimulation, and in the intervening gap region, support this functional dissociation. In addition to this distinction within the fundus of the central sulcus, the combination of high-resolution imaging and 3-D analysis techniques permitted localization of activation within areas 6, 4, 3a, 3b, 1, and 2 in the human. With the exception of area 4, which showed inconsistent activation during punctate tactile stimulation, activation in these areas in the human consistently paralleled the pattern of activity observed in previous studies of monkey cortex.
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INTRODUCTION |
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A consistent feature of mammalian sensory systems is the
rerepresentation of the sensory periphery in distinct cortical areas. Sensory cortical areas are defined by several criteria, including their
cytoarchitecture, pattern of connectivity, neuronal response properties, receptive field size, and the effect of lesions on perceptual capability (Kaas 1983). Over 30 areas have
been delineated within the monkey visual system (Kaas
1989
; Van Essen et al. 1992
), and several
regions, with similar response properties, have been defined recently
in the human cortex (DeYoe et al. 1996
; Engel 1996
; Sereno et al. 1995
; Tootell et al.
1995
, 1997
). Multiple auditory areas, segregated
by the pattern of responsiveness in tonotopic space, have been isolated
in monkey (Merzenich and Kaas 1980
; Morel et al.
1993
; Rauschaucker et al. 1995
) and human cortex (Talavage et al. 1996
).
In the somatosensory system, numerous anatomical and
physiological studies in monkeys support the existence of four distinct cortical areas within the central sulcus and postcentral gyrus (PoCG),
areas 3a, 3b, 1, and 2 (Brodmann 1994; Iwamura et
al. 1985
, 1993
; Jones 1985
;
Jones and Porter 1980
; Kaas et al. 1979
; Merzenich and Kaas 1980
; Merzenich et al.
1978
; Nelson et al. 1980
; Paul et al.
1972
; Sur et al. 1980
; Tommerdahl et al.
1996
). Neurons in areas 3b and 1 in the monkey possess discrete
tactile receptive fields (DiCarlo et al. 1998
;
Mountcastle and Powell 1959
; Pons et al.
1987
; Sur et al. 1980
) that are organized into mirror representations of the tactile body surface along the area 3b
and 1 border (Kaas et al. 1979
; Merzenich et al.
1978
). In the unanesthetized animal, a subset of neurons in
these areas also respond to deep and proprioceptive input
(Iwamura et al. 1993
; Taoka et al. 1998
),
and responses in these areas are modulated by motor activity
(Lebedev et al. 1994
; Nelson 1996
;
Nelson et al. 1991
; Prud'homme et al.
1994
). Area 2 contains neurons responsive to tactile and
proprioceptive stimulation (Hyvarinen and Poranen 1978
;
Iwamura et al. 1993
). These neurons demonstrate complex receptive field properties, including the integration of multimodal inputs and an increased concentration of direction-selective neurons (Ageranioti-Belanger and Chapman 1992
; Constanza
and Gardener 1980
; Hyvarinen and Poranen 1978
;
Iwamura and Tanaka 1996
; Iwamura et al.
1985
; Whitsel et al. 1972
). Neurons in area 3a,
located in the cortex in the fundus of the central sulcus, are
responsive to deep receptor and proprioceptive stimulation
(Iwamura et al. 1993
; Jones and Porter
1980
; Recanzone et al. 1992
; Taoka et al. 1998
). This area also possesses a minority of neurons with
tactile receptive fields (Iwamura et al. 1993
;
Strick and Preston 1982
; Tanji and Wise
1981
; Taoka et al. 1998
), and recent optical
imaging studies have demonstrated cutaneous nociceptive activation of this region (Tommerdahl et al. 1996
,
1998
).
In addition to the well-documented motor representations within the
precentral gyrus (PreCG) of the human and monkey, the PreCG also
receives somatosensory input. Distinct tactile and proprioceptive maps
have been reported in the anterior bank of the central sulcus, areas 4p
and 4a, respectively (Geyer et al. 1995; Strick
and Preston 1982
; Tanji and Wise 1981
). Further, the crown and anterior wall of the PreCG, Brodmann area 6, also possesses a tactile map (Gentilucci et al. 1988
;
Penfield and Rasmussen 1950
). The importance of these
regions to tactile perception is potentially significant: following
lesions of the PoCG, PreCG stimulation can evoke tactile sensations
(e.g., Penfield and Rasmussen 1950
), and lesions of the
PreCG in monkeys can lead to somatosensory neglect (Rizzolatti
et al. 1983
).
To investigate the organization of these representations in the hand
area of the human central sulcus region, we imaged subjects during two
protocols: punctate tactile stimulation and a kinesthetic/motor task.
To localize activation, we employed high-resolution functional magnetic
resonance imaging (fMRI) and whole-brain three-dimensional (3-D)
visualization techniques. High-resolution imaging was necessary to
localize precisely activation patterns within this region, because
cortical areas in the human can span less than a centimeter in the
anterior-posterior plane (White et al. 1997). The 3-D
reconstruction of the data provided further practical advantages,
offsetting the inherent ambiguity introduced by the curved path of the
central sulcus and neighboring gyri, which penetrate 2-D slice planes at a variety of angles, and make the precise assignment of activation to specific sulcal and gyral regions difficult (Gelnar et al. 1998
; Sastre-Janer et al. 1998
;
Sobel et al. 1993
).
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METHODS |
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Imaging techniques
Right-handed subjects (n = 5, age 20-31 yr, 2 women) were scanned in a 3-Tesla General Electric scanner with a birdcage head coil. Data were sampled from 16 coronal oblique slices oriented approximately parallel to the course of the central sulcus. Before and after functional scanning, a high resolution T1-weighted anatomical scan of these slice positions was taken (voxel size = 1.56 mm × 1.56 mm × 4.0 mm; TE = 57 ms). Functional runs were obtained using a gradient echo pulse sequence (voxel size = 3.125 mm × 3.125 mm × 4 mm; TR = 2,000 ms, TE = 50 ms). A total of 128 images per slice were taken for each 4:16 min functional run. Subjects received a minimum of four functional runs, two each for the tactile and kinesthetic/motor stimulation conditions; each subject's data were averaged within stimulation conditions.
Stimulation parameters
A functional run consisted of periods of stimulation (16 s) alternated with periods of no stimulation (16 s), for a total of eight ON/OFF cycles. The initial 16-s period was a period of no stimulation. During tactile runs, subjects were contacted with a 5.88log10.mg von Frey hair at a rate of 3 Hz. Within an epoch of stimulation, the position of contact varied over the glabrous surface of the palm, excluding the thenar eminence. Delivery of stimulation by the experimenter was timed to a metronome. During stimulation, the subject's hand was supported with firm but deformable foam cushions. In addition, two subjects also received von Frey stimulation of the third digit of the hand. The site of contact varied over all three segments of the glabrous surface of the finger (2 runs per subject). Subjects were instructed to keep their eyes closed during functional imaging, to attend to the stimulus during presentation, and to keep their eyes open between runs.
Kinesthetic/motor stimulation occurred at the same alternating cycle as
the tactile runs. Subjects held their right arm flexed at the elbow
with the hand above the chest. They flexed and extended their fingers
around the metacarpal and interphalangeal joints of the fingers and
thumb of the right hand at a rate of 3 Hz (Rao et al.
1996; Schlaug et al. 1996
), as if squeezing an
imaginary tennis ball. They did not touch their fingers either to
neighboring digits or to the palm surface. Prior to scanning, subjects
practiced squeezing at a 3 Hz rate. During scanning, subjects heard a
metronome set at 3 Hz and instructions every 16 s to "stop"
and "go." Subjects also received this auditory stimulation during
the tactile runs. All subjects were monitored visually for compliance
with squeezing rate during the scanning session. Due to the noise
generated by the scanner, one subject was unable to discriminate the
metronome consistently, and squeezed at a self-paced rate of 2-5 Hz;
this subject was able to detect the go and stop commands at the
beginning and end of each epoch.
Statistical analyses
A Fourier analysis was performed on the activation in each voxel
over the full functional scan period. An f test was then conducted, comparing the ratio of the power of the fMRI signal at the
stimulus frequency with those at all other frequencies, excluding
harmonics. To confirm the localization of activation patterns achieved
with the f test, and to permit use of the averaging software, a t-test analysis was also conducted. The
t-test analysis pooled signals across stimulation epochs and
compared it with the pooled signal from nonstimulation epochs, with a
2-s interval introduced to account for hemodynamic delay. Activation
patterns generated by these two statistics were well aligned (for
example, compare the activation patterns in individuals in Figs.
1 and 4B), with a more
restricted extent of activation identified by the t-test.
Analysis of the volume of the cortical area in the PreCG and PoCG
region in three subjects (Cardviews) (Kennedy et al.
1998) recommended a Bonferroni correction for the analysis of
~2,000 pixels. After making this correction, we employed a statistical threshold for significant activation of P < 0.01 for individual subject and average activation patterns.
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Anatomical analyses
The position of the central sulcus is variable among human
subjects (White et al. 1997). Because of this
variability, morphing brains into Talairach space, a coordinate system
that does not account for the position of cortical landmarks in the
reconstruction of individual brains, "blurs" central sulcus borders
when subjects are averaged (Woods 1996
). Therefore in
addition to analyzing our data in Talairach space to allow for
comparison with previous reports, we have addressed the anatomical
variability of the central sulcus in two ways. First, we analyzed the
position of activation in each subject relative to his or her specific
anatomy, an approach made possible through use of a high field-strength
fMRI scanner. This strategy allowed us to account for inter-subject
variability in the gross anatomy of the central sulcus region during
activation localization, and these anatomically specific analyses could
then be combined across subjects to record probabilistic activation maps. Second, we placed brains in a common coordinate space using a
technique that maximizes sulcal similarity (Fischl et al.
1998
, 2000
). This transformation allowed us to
take advantage of the increased signal-to-noise ratio generated by
averaging activation across subjects. In both approaches, the use of
whole-brain visualization techniques facilitated individual subject and
averaged data analysis.
Anatomical reconstruction
Cortical surface-based analysis techniques were conducted as
described in Dale and Sereno (1993), Dale et al.
(1998)
, and Fischl et al. (1998
,
2000
). Briefly, an initial SPGR high-resolution anatomical scan was taken for each subject (128 slices, 1.0 cubic mm;
head coil, 1.5 T GE or Siemens scanner). From this scan, all white
matter voxels were labeled, and the gray matter-white matter border
was tessellated to form a surface. The surface thus obtained was fitted
against MRI data, and surface defects were corrected, if needed, by
manual tracing. Following each functional scanning session, the surface
was aligned with the high-resolution T1 scan, to correct for
differences in the orientation and position of the brain in individual
experiments. Functional data were then interpolated onto the surface,
and the brain was inflated by an algorithm that employed curvature
reduction and local metric-preserving terms (Fischl et al.
1998
, 2000
). For all anatomical analyses, we
examined activity projected onto a 3-D rendering of the gray matter-white matter border of each individual's brain. To minimize the probability of partial volume contamination of signal across the
central sulcus, only pixels overlying white matter were included in the
analysis. In all subjects, the position of the gray matter-white matter border of the PreCG wall of the sulcus was
5 mm from the border of the PoCG wall. This affords a distance of greater than a
voxel width between the two regions of interest, decreasing the
probability of misattribution.
Localization of the central sulcus and definition of the hand area
The central sulcus was identified using two anatomical landmarks
(Kido et al. 1980; Sobel et al. 1993
).
First, on the lateral view of the reconstructed brain, the central
sulcus was defined as the sulcus immediately posterior to the
perpendicular intersection of the anterior-posterior oriented superior
frontal sulcus and the medial-lateral oriented precentral sulcus.
Second, on the medial view, the central sulcus was defined as the small
sulcus oriented dorsal-ventral on the dorsal surface of cortex, located anterior to the ascending, marginal branch of the cingulate sulcus. At
the midline, the central sulcus was limited in extent, but a few
millimeters lateral to the midline view was readily identifiable as a
deep sulcus.
The hand area was defined as the first posterior convexity
of the central sulcus lateral to the midline. This area has been described as an omega-shaped formation in the central sulcus in the
axial plane, and a hook-like folding of the cortical mantle in the
sagittal plane (White et al. 1997; Yousry et al.
1997
). The hand area is readily visible from the lateral view
of the reconstructed cortical surface (Fig. 1). Several studies using intracortical electrical stimulation or functional neuroimaging have
confirmed the presence of a motor and/or somatosensory hand representation in this anatomical location either explicitly
(Sastre-Janer et al. 1998
; Yousry et al.
1997
) or through the position of the hand representation in
their illustrations (Penfield and Rasmussen 1950
;
Uematsu et al. 1992
).
Assignment of activation to the probable position of areas
We used the sulcal and gyral pattern in individual subjects to
demarcate the probable position of areal borders defined by cytoarchitecture and receptor binding studies (Brodmann
1994; Geyer et al. 1997
; White et al.
1997
; Zilles et al. 1995
). We defined six
anatomical regions of interest centered over the hand area in each
subject. These regions corresponded to the cytoarchitectonic areas
surrounding the central sulcus: areas 6, 4, 3a, 3b, 1, and 2 (Brodmann 1994
; Geyer et al. 1997
;
White et al. 1997
). Although there is between-subject
variability in the correspondence between cytoarchitecture and gross
human neuroanatomy, separate examinations of the pattern of
cytoarchitecture within the human PreCG and PoCG support the following
subdivisions across subjects at the level of the hand area
(Brodmann 1994
; Geyer et al. 1995
; see Geyer et al. 1997
for a detailed assessment of
radioligand binding in the PoCG; White et al. 1997
, for
a detailed assessment of the cytoarchitectonic extent of areas 4, 3a,
and 3b in humans; and Jones and Porter 1980
, for a
review of the variability in the localization of area 3a in humans and
primates). Area 6 was defined as the anterior wall and crown of the
PreCG, area 4 as the anterior wall of the central sulcus, area 3a as
the cortex in the fundus of the central sulcus, area 3b as the
posterior bank of the central sulcus, area 1 as the crown of the PoCG,
and area 2 as the posterior wall of the PoCG. Because the extent of
these areas is less consistent across subjects, activation in the
transition regions (e.g., on the anterior edge of a gyral crown) was
designated as activation in a "border region" (thin wedges between
areas in Fig. 3), reducing the likelihood of misattribution. For the
tactile condition, the segregation of activation into these areas was
completed independently by two observers (CIM and
ACG), with agreement on 97% of assignments (29/30).
The displayed images in Figs. 1 and 4 were spatially filtered by averaging the statistical value at a surface vertex and its nearest neighbors on the reconstructed surface, for 15 iterations. This process is mathematically equivalent to spatially filtering with a Gaussian kernel with a SD on the order of 3 mm. This strategy is advantageous, as spatially filtering on the surface preempts the blurring of signal across cortical representations lining a sulcus, reducing the probability of mislocalization of activation. Anatomical analyses were conducted in tactile maps in three subjects with and without spatial filtering, with 100% agreement in segregation of activation into areas (18/18), and subsequent localization was conducted with spatially filtered data.
Group averages
Data were averaged as in Fischl et al. (1998,
2000
). The goal of this intersubject averaging approach
was to align individual cortical folding patterns. To achieve this
goal, the reconstructed surface of each individual subject was mapped
onto the unit sphere, using a maximally isometric transformation. These
surfaces were then morphed into register with an average, canonical
cortical surface, guided by a combination of folding-alignment
(sulcus/gyrus) and isometry preserving forces. The canonical cortical
surface was generated by computing the summary statistics describing
the folding patterns of 40 previously aligned surfaces. The folding alignment force encourages the registration of folding patterns that
are prominent and consistent across individuals, while the isometry
term prevents excessive compression/expansion of the surfaces, as well
as ensuring the invertibility of the mapping. Functional data were
averaged across subjects by taking the mean ± SD of the fMRI
signal at each time point, and calculating summary statistics from
these measures.
To localize signals in the average activation patterns, the tactile average and the kinesthetic/motor average were projected onto the 3-D gray matter-white matter reconstructions of each subject, and the position of activation relative to the probable areas was assessed. The patterns of activation were identical with respect to the location of areas across all subjects, with variability limited to the extent of the border regions between areas.
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RESULTS |
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Tactile and kinesthetic/motor stimulation each activated discrete areas within the central sulcus region. Here we describe the results for the five subjects analyzed individually, and then for the group average.
Individual subject analyses
Within the hand area, tactile stimulation of the palm activated foci within the PreCG and PoCG, with a "gap" region of nonactivation across the central sulcus in all subjects (n = 5/5 subjects). This pattern of activation can be seen in the palm and finger activation patterns (Fig. 1, left and middle). In contrast, kinesthetic/motor stimulation activated the PreCG, the gap region, and part of the PoCG as a single continuous region of activation in all subjects (Fig. 1, right). In the two subjects who received finger stimulation, the lateral border of kinesthetic/motor activation was approximately coextensive with the lateral boundary of activation during tactile finger stimulation, and the medial border of kinesthetic/motor activation was approximately coextensive with the medial border of activation during tactile palm stimulation (n = 2 subjects; Fig. 1).
Using the activation regions functionally defined by tactile stimulation of the palm, time series were generated for both stimulation conditions in each subject for the PreCG, gap, and PoCG regions. The Talairach coordinates for these three regions are shown in Table 1. The gap region in each individual was defined as the entire region between the PoCG and PreCG activated foci, bounded medially and laterally by the extent of these two activation patterns. As indicated by the statistical patterns, the PreCG and PoCG tactile regions showed sustained increases in percentage signal change during the tactile stimulation, whereas the gap region showed only a transient increase (0.3% signal change) followed by a return to baseline (Fig. 2, top left). During kinesthetic/motor activation, all three regions demonstrated increased percentage signal change (Fig. 2, top right). The signal increase in the gap region was significantly greater during the kinesthetic/motor stimulation than during the tactile stimulation (Gap: tactile 0.17 ± 0.29 vs. kinesthetic/motor 1.7 ± 0.71; mean ± SD, P < 0.01, paired 2-tailed t-test), but there was no significant difference in the amplitude of signal increase in the PoCG and PreCG regions for the two stimulation paradigms (PreCG: tactile, 0.97 ± 0.30% vs. kinesthetic/motor, 1.13 ± 0.53; PoCG: 0.93 ± 0.17 vs. 1.44 ± 0.58; P > 0.05; Fig. 2, bar graphs).
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As a companion analysis to the functional segregation of somatosensory
representations, we used the sulcal and gyral pattern in individual
subjects to demarcate anatomical borders that correspond to area
borders (Brodmann 1994; Geyer et al.
1997
; White et al. 1997
; Zilles et al.
1995
). We found that the cortex in the fundus of the central
sulcus, corresponding to area 3a, was active in only one of five
subjects during tactile stimulation: the single individual that
demonstrated activation in 3a also demonstrated a gap region (see Fig.
4 for overlaid activation patterns from all subjects). In contrast, the
same region was activated in all subjects during kinesthetic/motor
stimulation (Fig. 3). Tactile stimulation
activated the position of areas 6, 3b, and 1 in all subjects, area 2 in
four of five subjects, and area 4 in two of five subjects. In two
subjects, a pair of distinct regions of activation were present in the
PoCG, a larger anterior activation (included in the above PoCG
analysis), and a second smaller region located more posteriorly. In one
subject, two regions of activation were observed within area 6. Kinesthetic/motor stimulation activated areas 6, 4, 3a, 3b, and 1 in
all subjects, and area 2 in three of five subjects.
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Averaged data analyses
In addition to the analysis in individual subjects, we also averaged the tactile or kinesthetic/motor functional data across subjects. As in the individual tactile activation patterns, PreCG and anterior PoCG activation areas were segregated by a gap of nonactivation in the cortex in the fundus of the central sulcus (Fig. 4). In the tactile average, activation was present in the hand area in the PreCG in the position of area 6 and in the border region between areas 6 and 4. In the PoCG, activation was present in an anterior and a posterior focus. The position of the two activations in the PoCG corresponded to area 3b (anterior activation) and overlapping areas 1 and 2 (posterior activation). The kinesthetic/motor average revealed activation spanning the PreCG, gap, and part of the PoCG. The anterior border of the kinesthetic/motor activation was aligned with the anterior border of PreCG activation in the tactile activation, and the posterior edge extended into the anterior border of area 2.
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DISCUSSION |
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Using high-resolution fMRI and whole-brain visualization
techniques, we have described a region in the cortex in the fundus of
the central sulcus, in the position of area 3a, that is inactive during
punctate tactile stimulation, but is robustly activated during
kinesthetic/motor stimulation. Further, we localized activation to
specific positions within the PreCG and PoCG during both stimulation paradigms. These patterns were consistent among subjects in our sample
(all subjects showed the gap pattern of activation in the central
sulcus) and were confirmed in the across-subject averages. These
findings replicated a preliminary study that observed the same
activated regions using a 1.5-Tesla scanner and a 5-in. surface coil
(Moore et al. 1998).
Our goal in relating the position of functional activation in
individual subjects to the expected anatomical location of human areas
was to record a probabilistic activation map. With this map, human
activation patterns can then be related to reports on the monkey
central sulcus region that employ these anatomical borders to demarcate
sensory cortical areas (e.g., Kaas et al. 1979;
Merzenich et al. 1978
). We emphasize, however, that the assignment of functional activation to the probable position of areas
is not tantamount to a description of human sensory cortical areas;
without detailed cytoarchitecture, binding studies, myeloarchitecture, and patterns of efferent and afferent connectivity to account for the
variability in each subject's anatomical organization, the attribution
of areal borders is necessarily incomplete (Jones and Porter
1980
; Kaas 1983
; Roland and Zilles
1998
; Zilles et al. 1995
).
Comparison of the stimulus conditions
The cortical representations surrounding the central sulcus have
been implicated previously in two broadly defined domains: motor
activity and somatosensory perception. The two tasks employed in this
initial study of representations in the human hand area using 3-T fMRI
were chosen from the two extremes of this sensorimotor continuum. The
kinesthetic/motor condition is an active motor task that engages a
variety of peripheral receptors, including joint receptors, muscle
receptors and slowly adapting (SA) and fast-adapting (FA) skin
mechanoreceptors (Burgess et al. 1982; Edin and
Abbs 1991
; Hulliger et al. 1979
; Matthews
1982
). Perceptually, this condition evokes primarily
kinesthetic sensations and lacks a punctate tactile component. In
contrast, the punctate tactile condition is a passive sensory
stimulation that robustly drives skin mechanoreceptors
(Johansson and Valbo 1980
; Johansson et al.
1980
) and may also evoke muscle spindle activity (Burke
et al. 1976
; Roll and Vedel 1982
). Perceptually,
this condition evokes the sensation of discrete contact varying in
location on the glabrous surface of the palm at 3 Hz, without a
kinesthetic or motor component. The principal dissociation observed in
the activation generated by the two tasks was in the fundus of the
central sulcus, the position of area 3a in the human. The failure of
the punctate tactile condition to activate this region suggests that
its activation during the kinesthetic/motor condition does not result
primarily from the activation of low-threshold mechanoreceptors, which
are engaged in both conditions. Rather, activation in this region apparently derives from the ensemble of peripheral receptors and central neural activity driven by changes in finger position and/or active motor behavior.
Area 3a in humans and monkeys
Lesion, electrophysiological, and neuroanatomical studies of the
human central sulcus region have provided inconclusive evidence for the
existence of a distinct cortical area 3a, and/or of a distinct region
encoding proprioceptive information. Head (1920) concluded from the psychophysical evaluation of patients with cerebral
lesion that a cortical proprioceptive area existed in the central
sulcus region, independent of the representation of tactile perception.
Penfield and Rasmussen (1950)
and Corkin et al.
(1970)
also reported deficits in position sense following excisions of the PoCG hand area. Penfield and Rasmussen
(1950)
further observed that kinesthetic sensations were
frequently reported following electrical stimulation of the PoCG. These
authors, however, did not observe the segregation of distinct
somatosensory representations in the central sulcus region for
proprioceptive or for tactile processing. The cytoarchitectonic
definition of area 3a in the human (and monkey) has varied across
researchers (see Jones and Porter 1980
, for a review),
and the extent of this region shows greater variability between
subjects and has less rigid cytoarchitectonic borders, than other
regions within the central sulcus (Jones and Porter
1980
; White et al. 1997
; but see Geyer et
al. 1997
). Passive movement of the arm has been reported to
activate the Rolandic cortex in the human (Weiller et al.
1996
), but a recent positron-emission tomography (PET) study of
the vibration-induced motion illusion of the arm failed to activate
area 3a (Naito et al. 1999
).
Electrophysiological and lesion studies in the monkey cortex have
provided consistent evidence for a distinct representation in area 3a
(Iwamura et al. 1993; Kaas et al. 1979
;
Pons et al. 1992
; Recanzone et al. 1992
).
Area 3a in the monkey receives input from the ventral posterior
superior nucleus of the thalamus, which encodes deep and proprioceptive
inputs exclusively (Cusick et al. 1985
; Jones
1983
). Correspondingly, neurons in area 3a are driven
effectively by deep and proprioceptive receptor inputs (Iwamura et al. 1993
; Recanzone et al.
1992
; Strick and Preston 1982
; Taoka et
al. 1998
). Lesions of area 3a in the monkey lead to a decreased
representation of proprioceptive information in SII, whereas lesions of
areas 3b and 1 have little effect on the representation of deep and
proprioceptive input in SII (Pons et al. 1992
). In
psychophysical experiments in monkeys, lesions of areas 3b and 1 produce specific deficits in tactile discrimination (the perception of
roughness, grating orientation, and texture), and lesions of area 2 induce selective deficits in tasks requiring tactile and
proprioceptive integration (the perception of the shape or angle
of an object) (Carlson 1980
; Semmes and Porter 1972
; Semmes et al. 1974
). Neither set of
lesions induced a deficit in the perception of position sense
(Semmes et al. 1974
).
In agreement with these monkey studies, our data provide strong
evidence for a functionally distinct area 3a in humans. This region was
activated during kinesthetic/motor but not punctate tactile input,
consistent with the existence of a discrete representation that
participates in the perception of changes in body position. This
finding was supported by anatomically derived definitions of area 3a,
functionally defined activation borders, and by the pattern of
percentage signal change. Future studies in humans will be required to
further delineate the functional characteristics of area 3a,
specifically the importance of motor activity and attentional context
(Naito et al. 1999; Nelson 1984
,
1996
), and its role in processing nociceptive input
(Tommerdahl et al. 1996
, 1998
).
A potential concern regarding the differential signal observed in area
3a is that greater signal increase in neighboring representations during the kinesthetic/motor protocol, particularly in the PreCG, might
have extended nonspecifically into the cortex on the depth of the
central sulcus. If this type of nonspecific "revealed iceberg" effect was underlying the statistical changes we observed, the level of
activity in the PreCG or PoCG during the kinesthetic/motor condition
would be greater than the signal increase in area 3a, and the overall
pattern of increased signal change would parallel that recorded during
tactile stimulation. In contrast, the opposite pattern was observed:
there was greater signal change in the gap than in the PreCG or PoCG
during the kinesthetic/motor condition, a reversal of the pattern seen
in the tactile condition, supporting a functional dissociation between
the two conditions (Fig. 2). Further, we have employed a conservative
statistical threshold, a Bonferroni correction for the number of pixels
analyzed, which mitigates against the probability of false positives
(Locasio et al. 1997), and have localized activation to
the gray matter-white matter border, which minimizes the probability
of anatomical misattribution.
Activation in the PreCG and PoCG during tactile input
The activation observed with punctate tactile stimuli is in
general agreement with a variety of studies that have reported human
PoCG activation during nonpainful somatosensory stimulation (e.g.,
Allison et al. 1991; Boecker et al. 1996
;
Burton et al. 1997
; Coghill et al. 1994
;
Disbrow et al. 1998
; Fox et al. 1987
; Gelnar et al. 1998
; Hammeke et al. 1994
;
Kurth et al. 1998
; Lin et al. 1996
;
O'Sullivan et al. 1994
; Puce et al.
1995
; Roland and Larsen 1976
; Servos et
al. 1998
). Many of these studies did not localize activation to
discrete regions of the PoCG. Of those studies that reported more
specific anatomic localization during stimulation of the hand, three
basic patterns have emerged. First, fingertip stimulation with moving
gratings and haptic length discrimination tasks elicited dual
activation peaks in the anterior and posterior PoCG (PET)
(Burton et al. 1997
; O'Sullivan et al.
1994
; see also Lin et al. 1996
, for
activation of the central sulcus and postcentral sulcus using fMRI).
Second, electrical stimulation evoked dual peaks in the anterior PoCG
[somatosensory evoked potentials (SEP), Allison et al.
1991
; fMRI, Kurth et al. 1998
; but see
Puce et al. 1995
]. Third, discrete vibrotactile
stimulation of the fingertip, vibrating movement of the finger, and the
haptic discrimination of roughness activated the posterior PoCG (PET,
Burton et al. 1997
; O'Sullivan et al.
1994
; fMRI, Gelnar et al. 1998
, although these
authors also observed activity in more anterior PoCG regions in a
minority of subjects). Our findings are most similar to the activation
evoked by passive moving gratings contacting the fingertip (Burton et al. 1997
). Both studies employed a tactile
stimulus that changed position on the glabrous skin surface of the hand and would be anticipated to activate tactile receptive fields in areas
3b, 1, and 2.
Activation during tactile stimulation in the PreCG, corresponding to
area 6, is predicted by patients' reports of tactile sensation during
cortical stimulation of the crown of the PreCG (Nii et al.
1996; Penfield and Rasmussen 1950
;
Uematsu et al. 1996
), the presence of tactile receptive
fields in the macaque monkey (Gentilucci et al. 1988
;
Rizzolatti et al. 1981
), and the effect of lesions to
this area, which induce somatosensory neglect of the contralateral side
(Rizzolatti et al. 1983
). Area 4 also has been shown to
have distinct tactile and deep/proprioceptive representations in the
squirrel monkey (Strick and Preston 1982
), and the
macaque monkey (Tanji and Wise 1981
), a
dissociation that is supported by receptor binding and PET studies in
humans (Geyer et al. 1995
; Naito et al.
1999
). In these studies, the tactile representation (area 4p)
was located in the lower half of the anterior bank of the central
sulcus, adjacent to area 3a, and >90% of neurons contained cutaneous
receptive fields responsive to light moving contact, tapping, or hair
movement (Strick and Preston 1982
; Tanji and Wise
1981
).
We did not observe consistent activation in the anterior bank of the
central sulcus during tactile input. Only two of five subjects in the
individual subject analysis showed activation in this region (only 1 of
these subjects showed activation in the lower half of the anterior bank
of the central sulcus), and the tactile average did not reveal
activation in this region. This absence of significant activation may
be the product of the punctate tactile stimuli we employed. We did not
examine a moving tactile stimulus or vibratory stimulation of 10 Hz,
stimulus conditions that previously activated area 4p in humans
(Geyer et al. 1995
; Naito et al. 1999
),
nor did we administer the variety of tactile stimuli used to activate
individual receptive fields in this representation in previous monkey
studies (Strick and Preston 1982
; Tanji and Wise
1981
). Nevertheless, the data reported here do not support the
position that a high concentration of cutaneous receptive fields exists
in posterior area 4 in the human.
Although this signal did not achieve statistical significance, a small
stimulus transient was present in the gap during punctate tactile
stimulation (0.3% peak signal change, 0.17% mean signal change, Fig.
2). Activation of muscle spindles by the punctate tactile stimuli may
have contributed to this response (Burke et al. 1976;
Roll and Vedel 1982
). In three of five subjects, the gap
included area 4, and cutaneous receptive fields in this region or in
area 3a also might have contributed to this nonsignificant signal
increase (Iwamura et al. 1993
; Strick and Preston
1982
; Tanji and Wise 1981
; Taoka et al.
1998
). Studies in the unanesthetized monkey place the
concentration of cutaneous receptive fields in area 3a at
15%
(Iwamura et al. 1993
; Tanji and Wise
1981
; Taoka et al. 1998
). Similarly, the
percentage signal change in the gap region during tactile input is
between 10 and 15% of the signal change observed during
kinesthetic/motor stimulation (2.0% peak signal change, 1.7% mean
signal change). The temporal characteristics of the stimulus transient
evoked by tactile stimulation suggest that the neurons in this region
show rapid and sustained adaptation in response to punctate tactile stimulation.
Tactile activation in areas 3b and 1 in the human corresponds with the
suprathreshold receptive fields that have been recorded in the monkey
PoCG (Chapman and Ageranioti-Belanger 1991;
DiCarlo et al. 1998
; Iwamura et al. 1993
;
Johnson and Hsiao 1992
; Kaas et al. 1979
;
Manger et al. 1996
; Merzenich et al.
1978
; Mountcastle and Powell 1959
; Nelson
et al. 1980
; Paul et al. 1972
; Pons et al. 1985
; Sur et al. 1980
). These neurons are
effectively activated by the punctate von Frey stimulus employed in our
study (Jain et al. 1997
), and the rate of stimulation we
employed (3 Hz) is beneath the adaptation rate of the majority of
neurons in these regions (Sur et al. 1981
,
1984
). In individual subjects (4 of 5), and average
maps, activation in area 2 was localized to the anterior half of this
region. In the nonhuman primate, the anterior and posterior borders of
area 2 have been the subject of ongoing discussion (Jones et al.
1978
; Lewis et al. 1999
; Pons and Kaas 1986
). The position of area 2 in the current study
(based on receptor binding and cytoarchitecture in the human)
(Geyer et al. 1997
) is relatively more posterior. With a
more anterior placement of area 2, this region would have been
activated uniformly by the tactile and kinesthetic/motor conditions in
individual subjects and average maps (Fig. 4).
Conclusive delineation of fine somatotopy will require higher
resolution studies designed to answer this question. Nevertheless, the
data reported here may provide insight into detailed somatotopic organization in the human PoCG. In the average and in two individual subjects, dual activation regions were observed in the PoCG, localized anterior and posterior within the gyrus. This pattern is similar to the
mirror representations observed in the monkey PoCG [Kaas et al.
1979; Merzenich et al. 1978
; Nelson et
al. 1980
; see also Burton et al. (1997)
for a
similar observation in the human and Gelnar et al.
(1998)
for a diverging view]. Comparison of the finger and
palm representation in individual subjects demonstrates that, while
there is overlap in the two activation patterns, the center and extent
of the palm representation in the PoCG was more medial than the third
digit representation (n = 2 subjects, Fig. 1). This
more medial position is similar to owl and macaque monkey maps, where
the ulnar nerve representation (which was preferentially stimulated in
our study, as the thenar eminence was not contacted) is positioned more
medially than the third digit (Merzenich et al. 1978
;
Nelson et al. 1980
; Pons et al. 1987
).
Activation in the PreCG and PoCG during kinesthetic/motor input
Activation in the PreCG during the kinesthetic/motor protocol is
consistent with the well-documented position of the primary motor and
premotor cortices, as described by in vivo stimulation (e.g.,
Penfield and Rasmussen 1950; see Uematsu et al.
1992
, for a review) and functional imaging studies in the human
(e.g., Kim et al. 1993
; Rao et al. 1993
;
Roland et al. 1980
; Sanes et al. 1995
).
Activation in the PoCG during kinesthetic/motor stimulation has been
observed in several PET and fMRI studies that reported activation
spanning the PreCG, central sulcus, and PoCG during stimulation that
combined kinesthetic/motor grasping type movements with tactile
stimulation (Boecker et al. 1996
; Grafton et al. 1996
; O'Sullivan et al. 1994
; Rizzolatti
et al. 1996
) and without tactile stimulation
(Fink et al. 1997
). Engagement of areas 3b and 1 during
the kinesthetic/motor condition probably results from a variety of
inputs. Recordings from unanesthetized monkey preparations reveal a
significant minority of neurons in area 3b, and a lesser number in area
1, are deep or proprioceptive in character (Arezzo et al.
1981
; Iwamura et al. 1993
). As discussed above,
SA and FA skin mechanoreceptors in the fingers are activated by the
type of movement engaged in the kinesthetic/motor task (Burgess
et al. 1982
; Edin and Abbs 1991
; Hulliger
et al. 1979
; Matthews 1982
), and these receptors
should contribute to the activation of representations within the PoCG.
Also, this finding may in part result from the modulation of firing in
neurons in areas 3b and 1 during and prior to movement of the hand
(Jiang et al. 1990
; Lebedev et al. 1994
;
Nelson et al. 1991
; Prud'homme et al. 1994
; see Nelson 1996
for a review).
Conclusion
Prior to the introduction of modern extracellular recording
techniques, there was little appreciation of the submodality-specific representations of the body within the central sulcus region of humans
or monkeys (e.g., Penfield and Rasmussen 1950). With
their advent, the understanding of the organization of distinct
cortical areas in this region in monkeys advanced markedly (Kaas
et al. 1979
; Merzenich et al. 1978
). The current
progress in the resolution of hemodynamic imaging and reconstruction
techniques applied to the human cortex mirrors this advance in monkeys.
We are now able to address segregation in this region with relatively
high resolution. The fMRI data reported here, while lower resolution
than single unit techniques, present a strong correspondence with the
physiology of the monkey central sulcus region, especially with studies
of the unanesthetized monkey cortex (e.g., Iwamura et al.
1993
). This agreement suggests a conservation of somatosensory
cortical representations across species (Kaas 1983
;
Krubitzer 1995
). Further, this correlation provides a
point of cross-validation for the use of monkey physiology as a model
for the function of the human somatosensory cortex, and, by the same
token, suggests that the fMRI signal in the human somatosensory cortex
provides an accurate reflection of underlying neural activity in this region.
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ACKNOWLEDGMENTS |
---|
We thank T. Campbell and M. Foley for excellent technical support and Dr. Leah Krubitzer for critical comments on an earlier version of the manuscript.
This work was supported by a grant from the Spinal Cord Research Foundation/Paralyzed Veterans of America.
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FOOTNOTES |
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Address for reprint requests: C. I. Moore, NE20-329, Massachusetts Institute of Technology, Cambridge, MA 02139 (E-mail: cim{at}ai.mit.edu).
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 12 November 1999; accepted in final form 21 March 2000.
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REFERENCES |
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