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Cerebral Cortex Advance Access originally published online on September 14, 2005
Cerebral Cortex 2006 16(6):819-826; doi:10.1093/cercor/bhj025
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© The Author 2005. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oupjournals.org

Subarea-specific Suppressive Interaction in the BOLD Responses to Simultaneous Finger Stimulation in Human Primary Somatosensory Cortex: Evidence for Increasing Rostral-to-caudal Convergence

Jan Ruben, Thomas Krause, Birol Taskin, Felix Blankenburg, Matthias Moosmann and Arno Villringer

Charité — Universitätsmedizin Berlin, Berlin NeuroImaging Center and Department of Neurology, 10117 Berlin, Germany

Address correspondence to Jan Ruben, Charité — Universitätsmedizin Berlin, Berlin NeuroImaging Center and Department of Neurology, Schumannstrasse 20/21, 10117 Berlin, Germany. Email: jan.ruben{at}charite.de.


   Abstract
Top
 Abstract
Introduction
 Material and Methods
 Results
 Discussion
 Supplementary Material
 References
 
In the primary somatosensory cortex (SI) of non-human primates, receptive field properties have been shown to differ between its subareas with increasing convergence in areas 1 and 2 as compared with area 3b. In this study, we searched for a similar functional organization of human SI. We performed fMRI in healthy subjects during separate or simultaneous electrical stimulation of the second and third finger of the right hand. Activation patterns in response to stimulation of single fingers reflected the somatotopical arrangement within the hand area of SI. Somatotopy was more clear-cut in area 3b as compared with areas 1 and 2. The response to simultaneous stimulation was considerably smaller than the summed responses to separate stimulation of each finger alone, pointing to a suppressive interaction effect. A region-of-interest analysis in the representational areas of the second and third finger revealed subarea-specific differential suppressive interaction with an increase along the rostral-caudal axis (areas 3b, 1 and 2: 26, 32.7 and 42.2%, respectively). These findings on differences in the topographic as well as functional organization between subareas of SI support the notion of increasing convergence and integration from area 3b to areas 1 and 2 in human subjects.

Key Words: electrical stimulation • fMRI • SI • somatotopy • suppressice interaction


   Introduction
Top
 Abstract
 Introduction
Material and Methods
 Results
 Discussion
 Supplementary Material
 References
 
The primary somatosensory cortex (SI) of primates constitutes the main projection area of somatosensory afferents and comprises four different cytoarchitectonical subdivisions (areas 3a, 3b, 1 and 2) oriented along the rostro-caudal axis of the postcentral gyrus (Brodmann, 1909Go; Vogt and Vogt, 1919Go). Each area contains a representational map of the contralateral body surface (Merzenich et al., 1978Go; Kaas et al., 1979Go; Nelson et al., 1980Go; Pons et al., 1985Go). However, convergence of afferents from adjacent body areas seems to differ between subdivisions of SI. Whereas neurons in area 3b have receptive fields restricted to single fingers or even parts of single fingers, neurons in the more caudally located areas 1 and 2 have increasingly larger receptive fields (Iwamura et al., 1980Go, 1983aGo,bGo, 1993Go; Iwamura, 1998Go).

Evidence has been given that processing of simultaneous multi-site stimulation differs from single-site stimulation, i.e. the responses of two simultaneously applied stimuli do not add up linearly, pointing to an underlying suppressive interaction process. Such effects have been observed in SI in animal studies, e.g. by intracellular recordings of excitatory postsynaptic potentials in response to stimulation of different forelimb nerves in the cat (Macgillis et al., 1983Go), and in the rat during simultaneous whisker and forelimb stimulation using optical intrinsic signal imaging (Blood and Toga, 1998Go). For humans, interaction has been found to already emerge at the subcortical level, but it occurs predominantly in SI (Hsieh et al., 1995Go). In early cortical somatosensory-evoked potential (SEP) components, the responses to simultaneous stimulation of two fingers of the same hand are considerably smaller than the summed responses to separate finger stimulation (Gandevia et al., 1983Go; Hsieh et al., 1995Go). Comparable results have been obtained employing magnetencephalography (MEG) (Biermann et al., 1998Go; Ishibashi et al., 2000Go; Hoechstetter et al., 2001Go). In SEP recordings, interaction was reported for components presumably generated in area 3b as well as in area 1, whereas in somatosensory-evoked fields (SEFs) interaction was demonstrated mainly for area 3b, since this method is essentially sensitive to tangentially orientated sources. Though both techniques allow for a more direct measurement of neuronal activity at high temporal resolution, the accuracy of assigning the contributions of the different subareas of SI to the measured signals is limited. In comparison, functional magnetic resonance imaging (fMRI) offers the complementary advantage of obtaining temporally integrated responses that can be allocated to the anatomical structures of the postcentral gyrus with larger accuracy.

fMRI is capable of resolving the somatotopic representations in different subdivisions in human SI when fingers are stimulated separately (Gelnar et al., 1998Go; Kurth et al., 1998Go; Maldjian et al., 1999Go; Francis et al., 2000Go; Kurth et al., 2000Go; Ruben et al., 2001Go; Deuchert et al., 2002Go). In the current study we applied event-related fMRI at high spatial resolution during separate as well as simultaneous electrical stimulation of two adjacent fingers to address the following questions:

Which subdivisions within SI exhibit interaction?
Are there quantitative differences in interaction between the subdivisions of SI?


   Material and Methods
Top
 Abstract
 Introduction
 Material and Methods
Results
 Discussion
 Supplementary Material
 References
 
Subjects

Twelve healthy volunteers (eight male; mean age 26.7 years, range 23–31 years; 11 right-handed, one left-handed) without any history of neurological or psychiatric disease participated in this study. The study was approved by the local ethics committee and written consent was obtained from each subject prior to investigation.

Stimulus Application

Somatosensory stimulation consisted of innocuous electrical stimuli generated by two constant-current stimulator devices (Digitimer Limited, Welwyn Garden City, Hertfordshire, UK). The following stimulation conditions were applied: separate stimulation of the second finger, separate stimulation of the third finger, and simultaneous stimulation of the second and the third finger of the right hand (Fig. 1A).


Figure 1
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  		Figure 1. (A) Illustration of the stimulation paradigm consisting of electrical stimulation of the second finger, the third finger, and both fingers simultaneously. Stimuli and additional null events were presented in a randomised order with a range of ISIs varying from 3 to 9 s at 1 s steps (mean ISI of 6 s). (B) Illustration of the statistical model used to determine interaction. Regressor d2 contained all events when the second finger was stimulated; regressor d3, analogously, contained all events when the third finger was stimulated. The interaction term (regressor) was modelled for the cases of simultaneous stimulation of the second and the third finger, and thus reveals variance that is not explained by the regressor for d2 or d3, i.e. it indicates suppressive or facilitory interaction.

 
Somatosensory stimulation consisted of a train of monophasic square-wave current pulses (four pulses, single pulse duration = 0.2 ms, frequency = 4 Hz, train duration = 750 ms) delivered via self-adhesive electrodes to the tips of the second and the third finger (cathode proximal, anode–cathode separation 1cm). The sensory as well as the pain thresholds were determined for both stimulation sites (using the method of limits). Detection thresholds were 1.9 ± 0.2 mA (mean ± SD) for the second finger and 1.6 ± 0.2 mA for the third finger; pain thresholds were 7.0 ± 2.3 and 6.6 ± 2.4 mA, respectively. In order to avoid potential saturation of the blood oxygenation level-dependent (BOLD) response due to high stimulus intensities, applied current amplitudes were individually adjusted according to the following formula: perception threshold for second finger + perception threshold for third finger + 0.5 mA. From this base intensity, the intensity delivered to the finger associated with the stronger percept was successively lowered until it was equal to that of the other finger. The resulting stimulus intensities applied during fMRI were 3.9 ± 0.4 mA for the second finger and 3.6 ± 0.3 mA for the third finger, and were considerably lower than the respective pain thresholds.

fMRI Setup

Imaging was performed on a 1.5 T scanner (Magnetom Vision, Siemens, Erlangen, Germany) using a surface coil (CP Flex large). The surface coil was centred over the left parietal cortex approximately at the C3' position according to the extended 10/20 EEG system. The subject's head was immobilized by means of fixation tapes to minimize movement-related artefacts. For functional measurements, blood oxygenation level-dependent (BOLD) sensitive (Bandettini et al., 1992Go; Kwong et al., 1992Go; Ogawa et al., 1992Go; Frahm et al., 1992Go) echoplanar images (TR = 3 s, TE = 66 ms, flip angle = 90°) were acquired consisting of nine axial slices encompassing the hand area of SI (FOV = 256 mm, matrix = 128 x 128, voxel size = 2 x 2 x 3 mm, gap 1 mm). For all subjects, three successive runs in an event-related design were performed (Burock et al., 1998Go; Dale, 1999Go). Within a single run of 250 images, each stimulation condition was applied 28 times with an equal number of null events in a randomized order, with interstimulus intervals (ISIs) uniformly distributed in the range of 3–9 s at 1 s steps (mean ISI = 6 s); thus, repetitive stimulation was unlikely to generate a potential decrease in stimulus responses (adaptation). For anatomical co-registration, an MPRAGE (magnetization prepared rapid gradient echo) sequence (TR = 9.7 ms, TE = 4 ms, flip angle = 12°, voxel size = 1 x 1 x 1 mm) covering the whole brain was used to acquire a high resolution T1-weighted dataset.

Data Analysis

Imaging data were analysed using SPM99 (Wellcome Department of Cognitive Neurology, London, UK). The initial five volumes of each run were discarded from further analysis due to T1 saturation effects. Functional volumes were realigned to the first volume of the respective subject, slice-time corrected, normalized into MNI (Montreal Neurological Institute) space (resolution of 2 x 2 x 2 mm), spatially smoothed (Gaussian Kernel, full width at half maximum = 4 x 4 x 8 mm), and voxel time-series were high- and low-pass filtered.

For analysis of fMRI time series by multiple regression analysis we applied the well-established general linear model approach (Friston et al., 1995Go). Evidence for the validity of this linear approach for human SI has been given experimentally (Arthurs et al., 2000Go; Backes et al., 2000Go). Voxel time series were modelled using event-related regressors for each condition and convolved with the hemodynamic response function. Three regressors were defined (Fig. 1B): the regressor d2 contained all events when the second finger was stimulated, i.e. separate as well as simultaneous stimulation; the regressor d3 was defined correspondingly. Because we hypothesized that simultaneous stimulation of d2 and d3 would give a smaller response (i.e. parameter estimate) than predicted by adding up the responses to the stimuli when applied separately, we included an interaction term as the third regressor that was created by multiplying the regressors of d2 and d3. Negative parameter estimates for this regressor indicate that the effect of simultaneous stimulation is smaller than the sum of the separate stimulations, positive parameter estimates indicate a stronger effect. The negative contrast (‘suppressive interaction’, 0 0 –1) thus yields voxels with suppressive interaction and the positive contrast (‘facilitation’, 0 0 1) shows where facilitation is prevalent. The response to simultaneous stimulation (d2d3) is given by adding the parameter estimate of the third regressor to the sum of parameter estimates for d2 and d3:

Formula 1(1)
For statistical inference, a fixed effects analysis was performed on the subjects exhibiting significant activation of SI (P < 10–3) for the regressor d2 and d3 in single subject analysis (n = 10).

To test for subtle interaction effects within subregions of SI which might not have been detectable in the voxelwise analysis described above, we performed an additional region-of-interest (ROI) analysis. A ROI for SI was defined as the merged representation sites of the second and the third finger at an uncorrected P < 10–5 obtained from the group analysis. Interaction ratios (IRs) were then determined from the parameter estimates for each voxel within this ROI in analogy to previous reports (Hsieh et al., 1995Go) using the following formula:

Formula 2(2)
Inserting equation (1) into (2) gives:

Formula 3(3)
To quantify differential interaction between subareas of SI, this ROI was further subdivided. However, cytoarchitectonically defined subareas and interareal borders cannot be identified precisely based on anatomical landmarks alone due to high interindividual variability (Geyer et al., 1999Go). For this reason, the subareas within this SI-ROI were specified in line with criteria used consistently in numerous recent imaging studies (Lin et al., 1996Go; Burton et al., 1997Go; Gelnar et al., 1998Go; Servos et al., 1998Go; Francis et al., 2000Go; Moore et al., 2000Go; Krause et al., 2001Go; Deuchert et al., 2002Go; Blankenburg et al., 2003Go) for an operational definition. Accordingly, the posterior wall of the central sulcus and the adjacent anterior lip of the postcentral gyrus comprises area 3b, the crest of the postcentral gyrus area 1, and the anterior wall of the postcentral sulcus area 2. Anatomical parcellation (see also Fig. 4B) was performed on an average T1-weighted image obtained from all single subject T1 images. Due to the inevitable blurring of anatomical structures in the average brain, for visualization purposes group analysis data are finally presented on an individual brain that matched the pericentral region of the average brain best; the superposition of data on the average T1-weighted brain is additionally given in the Supplementary Material. The resulting IRs were then averaged across all voxels for each operationally defined subarea separately, and t-statistics were used to compare the mean IRs between subareas (post-hoc Bonferoni corrected).


Figure 4
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  		Figure 4. (A) Color-coded map of interaction ratios (IRs) for the group superimposed on T1-weighted images of an individual subject. The calculation of the map was based on a ROI comprising all activated voxels for d2 or d3 within SI at a threshold of P < 10–5. Interaction ratios can be seen to increase along the rostro-to-caudal direction of the postcentral gyrus. IRs are displayed for the range of 10–50%. (B) Illustration for the subsequent ROI analysis in order to determine interaction ratios for the SI subareas 3b, 1 and 2. Voxels within the posterior wall of the central sulcus and the adjacent anterior lip of the postcentral gyrus were assigned to area 3b (green), those on the crest of the postcentral gyrus to area 1 (red) and those within the anterior wall of the postcentral sulcus to area 2. (blue). (C) Distribution of IRs for areas 3b, 1 and 2. Mean IR for the area 3b ROI was 26%, for the area 1 ROI 32.7% and for the area 2 ROI 42.2% (indicated by vertical bar).

 
To account for a potential influence of interindividual variability regarding the location of interareal borders (Geyer et al., 1999Go) on the resulting interaction ratios, we shifted the respective operationally defined borders in an additional analysis. The border between area 3b and area 1 was shifted in the rostral as well as the caudal direction by 50% of the activation volume of area 3b. Accordingly, the border between area 1 and area 2 was shifted by 50% of the activation volume of area 2 in the rostral as well as caudal direction. Then again, IRs were calculated for the resulting subareas as described above.


   Results
Top
 Abstract
 Introduction
 Material and Methods
 Results
Discussion
 Supplementary Material
 References
 
In the group analysis, electrical stimulation of the second and the third finger led to statistically highly significant increases in fMRI signal intensity within the hand area of the postcentral gyrus. These activations comprised multiple foci across the postcentral gyrus which were located within the posterior wall of the central sulcus, within the crown of the postcentral gyrus, and within the anterior wall of the postcentral sulcus, presumably corresponding to area 3b, area 1 and area 2, respectively. No significant activation was seen in the fundus of the central sulcus in projection to presumptive area 3a.

In all subareas, activations in response to stimulation of the second and third finger showed considerable overlap. In area 3b, the respective activation maxima exhibited the known somatotopical arrangement with the third finger representation at a more superior, posterior and medial location as compared with the second finger; the Euclidian distance between both representation maxima was 10.8 mm. The somatotopic arrangement of activation foci within area 3b is illustrated in Figure 2. In contrast to area 3b, locations of finger representations in areas 1 and 2 shared similar coordinates, resulting in smaller Euclidian distances of 3.5 mm in both area 1 and area 2.


Figure 2
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  		Figure 2. T-maps for the group for d2 and d3 superimposed on T1-weighted images of an individual subject. Representation sites based on the most significant voxels differ from each other within the posterior wall of the central sulcus, presumably corresponding to area 3b (asterisk), exhibiting a somatotopical arrangement with the representation site of d3 at a more medial, posterior and superior position. In comparison, the more caudally located representation sites, presumably corresponding to areas 1 and 2 (circle), showed considerable overlap for d2 and d3. For delineation of overlapping voxels, the third column shows the superposition of the maps of d2 and d3 (d2, green; d3, magenta; overlap, white).

 
The T-map for the contrast ‘suppressive interaction’ thresholded at P < 10–5 (uncorrected for multiple comparisons) revealed an activation cluster on the crest of the postcentral gyrus, presumably corresponding to area 1 (Fig. 3). At a lower threshold of P < 10–3 activated voxels could also be specified corresponding to area 2; however, no significant activation was seen within the anterior wall of the central sulcus (area 3b). By the contrast ‘facilitation’ no significant voxels could be specified in SI (P < 10–3).


Figure 3
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  		Figure 3. T-map for the group for the interaction contrast superimposed on T1-weighted images of an individual subject, thresholded at an uncorrected P < 10–5. Significant interaction can be observed in SI. In more detail, this interaction was seen on the crest of postcentral gyrus, presumably corresponding to area 1. At a lower threshold of P < 10–3, interaction was also seen within area 2, whereas no interaction was statistically significant within area 3b (data not shown).

 
In a different approach, suppressive interaction was determined and quantified by a ROI-analysis based on the merged representations of the second and the third finger in SI, as shown in the interaction ratio map (Fig. 4). With this approach, suppressive interaction can be seen to be prevalent also within area 3b. Furthermore, IRs can be seen to gradually increase along the rostral-to-caudal axis, i.e. from area 3b to areas 1 and 2. Within this ROI, no voxels with negative IRs were obtained, indicating that there were no voxels exhibiting facilitation.

The subarea-specific ROI analysis based on the initial operationally defined subareas revealed different degrees of suppressive interaction between subareas of SI: for the subareas 3b, 1 and 2, the IRs (mean ± SD) were 26.0 ± 7.6, 32.7 ± 10.1 and 42.2 ± 9.2%, respectively, and were significantly different (P < 10–3, Student's t-test).

Shifting the borders between subareas 3b and 1, and between subareas 1 and 2, respectively, revealed a similar pattern of mean IRs as described above with an increase from area 3b to areas 1 and 2. Shifting the border between areas 3b and 1 in the rostral direction yielded interaction ratios of 22.7 ± 7.0% for area 3b and 32.4 ± 9.9% for area 1; shifting this border in the caudal direction yielded interaction ratios of 26.9 ± 7.3% for area 3b and 33.2 ± 10.3% for area 1 (difference in IRs between areas 3b and 1 statistically significant for both cases, P < 10–3, Student's t-test). Shifting the border between area 1 and area 2 in the rostral direction yielded IRs of 32.1 ± 9.9% for area 1 and 40.0 ± 10.1% for area 2; shifting it in the caudal direction gave IRs of 34.3 ± 10.5% for area 1 and 40.8 ± 10.4% for area 2 (difference in IRs between areas 1 and 2 statistically significant for both cases, P < 10–3, Student's t-test).


   Discussion
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Discussion
Supplementary Material
 References
 
In the present study, we show a substantial suppressive interaction in BOLD responses within human primary somatosensory cortex: the response to simultaneous stimulation was considerably smaller than the sum of the responses to separate stimulation of the second and the third finger. The main finding is that this suppressive interaction was subarea-specific and increased along the rostro-caudal axis from area 3b to areas 1 and 2.

Suppressive interaction was assessed by two different approaches: on the basis of the interaction contrast, interaction was determined in terms of significance. By this analysis, suppressive interaction was detected in area 1, at a lower threshold also in projection to area 2. However, since responses to finger stimulation can differ between subareas of SI, it is necessary to relate the absolute amount of interaction to the sum of single finger responses in order to obtain a relative measure for the degree of interaction as expressed in the IR (see Materials and Methods) that is independent from the level of significance. As a result, while the interaction contrast specified area 1 as the site with the largest absolute interaction, the interaction ratio was maximal within area 2. The IR map demonstrated that interaction was also prevalent within area 3b. Furthermore, the IR map clearly showed that suppressive interaction increased along the rostral-to-caudal direction. Consequently, subarea-related mean IRs could be determined for the operationally defined areas: 26% for area 3b, 32.7% for area 1 and 42.2% for area 2.

A crucial issue concerning our main finding of subarea-specific different interaction ratios might be the anatomical parcellation of SI into different subareas. As stated in Material and Methods, a parcellation based on macroanatomical landmarks alone cannot be clear-cut due to high intersubject variability (Geyer et al., 1999Go), although it has been commonly used in numerous recent imaging studies by similar criteria as in the current study (Lin et al., 1996Go; Burton et al., 1997Go; Gelnar et al., 1998Go; Servos et al., 1998Go; Francis et al., 2000Go; Moore et al., 2000Go; Krause et al., 2001Go; Deuchert et al., 2002Go; Blankenburg et al., 2003Go). In that way, since a definite parcellation is only possible in a cytoarchitectonic study, our parcellation represents an operational definition of subareas. Nevertheless, significant differences in IRs are still observable when the borders between areas 3b and 1 and between areas 1 and 2 were shifted towards the rostral as well as caudal direction. This approach yielded a very similar pattern of significantly different interaction ratios, increasing from area 3b to areas 1 and 2. It thus principally confirms that the IRs obtained for the operationally defined subareas are not due to an erroneous random choice of borders between subareas and strongly supports our finding of an increase in interaction ratios in the rostral-to-caudal direction.

In various animal studies, a sublinear summation during simultaneous multi-site stimulation in comparison with separate stimulation has been described by different methods: electrophysiologically, for instance, in whisker barrel cortex in terms of spiking activity and in cat's SI on the basis of intracellularly recorded postsynaptic potentials (Macgillis et al., 1983Go; Mirabella et al., 2001Go), as well as in vascular/metabolic responses using optical intrinsic-signal imaging in rats and monkey's area 3b (Blood and Toga, 1998Go; Chen et al., 2003Go). Moreover, our findings on interaction in SI are in general agreement with studies in humans assessing far field potentials recorded from the scalp, i.e. SEPs. An earlier study reported interaction ratios of up to 50% in responses evoked by separate and simultaneous stimulation of the second and the third finger, although no separation of certain components of the SEPs was performed (Gandevia et al., 1983Go). In the study by Hsieh et al. (1995)Go, evoked potentials in response to stimulation of the second and the third finger were obtained intraoperatively, and an interaction ratio of 27.0% was determined for the N20 component and of 35.9% for the P25 component of the SEP. The N20 is presumably generated in area 3b, whereas area 1 is regarded as a likely generator of the P25 (Allison et al., 1989Go, 1991Go). These interaction ratios are strikingly similar to those obtained in the current study, although the responses obtained in BOLD-signal fMRI represent temporally integrated signals that cannot be directly compared with specific components of the SEP or SEF. Comparable results of interaction in early SEF components have also been obtained in recent studies investigating the responses to simultaneous multi-site mechanical stimulation on the same finger (Hoechstetter et al., 2001Go) or electrical stimulation of adjacent finger pairs (Biermann et al., 1998Go; Ishibashi et al., 2000Go). However, due to methodological constraints of MEG in detecting radially oriented sources, these results were mainly assigned to area 3b. Our results strongly suggest that the interactions observed within human SI in the electrophysiological signals are paralleled by corresponding changes in the BOLD responses.

In principle, interaction can be physiologically explained by nonlinear signal integration in interconnected target principal neurons or by inhibition of principal neurons due to coactivation of surrounding inhibitory interneurons. Recording of excitatory postsynaptic potentials of cortical neurons in SI of cats revealed that both mechanisms are involved in processing of simultaneous multi-site stimulation (Macgillis et al., 1983Go). The impact of activity of inhibitory interneurons, which represents an energy demanding process, on regional cerebral blood flow and thus the BOLD signal is still matter of debate (for reviews, see Lauritzen, 2001Go; Ritter and Villringer, 2002Go; Lauritzen and Gold, 2003Go). In the case of a physiologically relevant inhibitory interneuron activity, a divergence between neural activity and vascular response is possible, as indicated by Matthiesen et al. (1998)Go, who stimulated cerebellar parallel fibres evoking monosynaptic excitatory and disynaptic inhibitory postsynaptic potentials in Purkinje cells, which resulted in a net decrease in spike rate of these target cells but was accompanied by an increase in laser Doppler flow.

Increasing suppressive interaction in areas 1 and 2 compared with area 3b as observed in the current study may have its physiological basis in the different receptive field characteristics of subareas of SI. In our study we found evidence for an increase of topographical convergence in the rostral-to-caudal direction. Stimulation of the second and third fingers resulted in activation patterns which reflected the medial to lateral somatotopical arrangement of finger representations in SI which was first demonstrated invasively by electrical stimulation of the cortex (Penfield and Boldrey, 1937Go). Regarding the subareas, this somatotopical arrangement was more clear-cut in area 3b as compared with areas 1 and 2 as reflected by the different Euclidian distances between the representations of the two fingers (10.8 mm for area 3b, each 3.5 mm for areas 1 and 2). For area 3b, the reported distance is in general agreement with results from other neuroimaging studies in humans (Gelnar et al., 1998Go; Biermann et al., 1998Go; Kurth et al., 2000Go). Regarding the less clear-cut somatotopy within areas 1 and 2 compared with area 3b, in a recent event-related fMRI-study similar results of smaller distances were obtained for the non-adjacent fingers 2 and 5 (Deuchert et al., 2002Go). In addition, using fMRI it was demonstrated that the overlap between the representation sites of the fingers 2 and 3 increased from area 3b to area 1/2 (Krause et al., 2001Go). These observations point to a different topographic organization of area 3b as compared with areas 1 and 2 similar to that described in non-human primates. Microelectrode recordings in non-human primates have shown that the majority of neurons in area 3b have receptive fields comprising a single finger or even parts of a single finger, whereas in areas 1 and 2 a continuous increase in the number of neurons with receptive fields covering multiple fingers was measured; as a consequence, the representations of fingers were found to be rather overlapping within areas 1 and 2 (Iwamura et al., 1980Go, 1983aGo, bGo, 1993Go).

Facilitation effects have been described in an SEP study using near-threshold intensities (Gandevia et al., 1983Go). In our study we used intermediate stimulus intensities in order to avoid a possible saturation of the hemodynamic response, which, however, might have been too high to mediate any facilitory effects.

In summary, this study provides evidence for interaction in the BOLD responses due to simultaneous stimulation of two adjacent fingers within primary somatosensory cortex of humans. Interaction was more pronounced within areas 1 and 2 as compared with area 3b. In parallel, the somatotopical arrangement was less clear-cut within areas 1 and 2 as compared with area 3b. This is in line with evidence for a rostro-to-caudal increase in convergence within SI and concepts suggesting a hierarchical processing with 3b as the primary projection area of somatosensory information (‘SI-proper’) whereas in the more caudal parts of SI information is increasingly integrated (Kaas, 1983Go; Iwamura et al., 1993Go; Iwamura, 1998Go).


   Supplementary Material
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Discussion
 Supplementary Material
References
 
Supplementary material can be found at: http://www.cercor.oxfordjournals.org/


   Acknowledgments
 
We thank Dr H.R. Heekeren for helpful discussion on the manuscript. This work was supported by the Bundesministerium für Bildung und Forschung (‘Berlin NeuroImaging Center’).


   References
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Discussion
 Supplementary Material
 References
 
Allison T, McCarthy G, Wood CC, Darcey TM, Spencer DD, Williamson PD (1989) Human cortical potentials evoked by stimulation of the median nerve. II. Cytoarchitectonic areas generating short-latency activity. J Neurophysiol 62:694–710.[Abstract/Free Full Text]

Allison T, McCarthy G, Wood CC, Jones SJ (1991) Potentials evoked in human and monkey cerebral cortex by stimulation of the median nerve. A review of scalp and intracranial recordings. Brain 114:2465–2503.[Abstract/Free Full Text]

Arthurs OJ, Williams EJ, Carpenter TA, Pickard JD, Boniface SJ (2000) Linear coupling between functional magnetic resonance imaging and evoked potential amplitude in human somatosensory cortex. Neuroscience 101:803–806.[CrossRef][Web of Science][Medline]

Backes WH, Mess WH, Kranen-Mastenbroek V, Reulen JP (2000) Somatosensory cortex responses to median nerve stimulation: fMRI effects of current amplitude and selective attention. Clin Neurophysiol 111:1738–1744.[CrossRef][Web of Science][Medline]

Bandettini PA, Wong EC, Hinks RS, Tikofsky RS, Hyde JS (1992) Time course EPI of human brain function during task activation. Magn Reson Med 25:390–397.[Web of Science][Medline]

Biermann K, Schmitz F, Witte OW, Konczak J, Freund HJ, Schnitzler A (1998) Interaction of finger representation in the human first somatosensory cortex: a neuromagnetic study. Neurosci Lett 251:13–16.[CrossRef][Web of Science][Medline]

Blankenburg F, Ruben J, Meyer R, Schwiemann J, Villringer A (2003) Evidence for a rostral-to-caudal somatotopic organization in human primary somatosensory cortex with mirror-reversal in areas 3b and 1. Cereb Cortex 13:987–993.[Abstract/Free Full Text]

Blood AJ, Toga AW (1998) Optical intrinsic signal imaging responses are modulated in rodent somatosensory cortex during simultaneous whisker and forelimb stimulation. J Cereb Blood Flow Metab 18:968–977.[CrossRef][Web of Science][Medline]

Brodmann K (1909) Vergleichende Lokalisationslehre der Großhirnrinde. Leipzig: J.A. Barth.

Burock MA, Buckner RL, Woldorff MG, Rosen BR, Dale AM (1998) Randomized event-related experimental designs allow for extremely rapid presentation rates using functional MRI. Neuroreport 9:3735–3739.[Web of Science][Medline]

Burton H, MacLeod AM, Videen TO, Raichle ME (1997) Multiple foci in parietal and frontal cortex activated by rubbing embossed grating patterns across fingerpads: a positron emission tomography study in humans. Cereb Cortex 7:3–17.[Abstract/Free Full Text]

Chen LM, Friedman RM, Roe AW (2003) Optical imaging of a tactile illusion in area 3b of the primary somatosensory cortex. Science 302:881–885.[Abstract/Free Full Text]

Dale AM (1999) Optimal experimental design for event-related fMRI. Hum Brain Mapp 8:109–114.[CrossRef][Web of Science][Medline]

Deuchert M, Ruben J, Schwiemann J, Meyer R, Thees S, Krause T, Blankenburg F, Villringer K, Kurth R, Curio G, Villringer A (2002) Event-related fMRI of the somatosensory system using electrical finger stimulation. Neuroreport 13:365–369.[CrossRef][Web of Science][Medline]

Frahm J, Bruhn H, Merboldt KD, Hanicke W (1992) Dynamic MR imaging of human brain oxygenation during rest and photic stimulation. J Magn Reson Imag 2:501–505.[Web of Science][Medline]

Francis ST, Kelly EF, Bowtell R, Dunseath WJ, Folger SE, McGlone F (2000) fMRI of the responses to vibratory stimulation of digit tips. Neuroimage 11:188–202.[CrossRef][Web of Science][Medline]

Friston K, Holmes A, Worsley KJ, Poline JB, Frith CD, Frackowiak RS (1995) Statistical parametric maps in functional imaging: a general linear approach. Hum Brain Mapp 2:189–210.[CrossRef]

Gandevia SC, Burke D, McKeon BB (1983) Convergence in the somatosensory pathway between cutaneous afferents from the index and middle fingers in man. Exp Brain Res 50:415–425.[Web of Science][Medline]

Gelnar PA, Krauss BR, Szeverenyi NM, Apkarian AV (1998) Fingertip representation in the human somatosensory cortex: an fMRI study. Neuroimage 7:261–283.[CrossRef][Web of Science][Medline]

Geyer S, Schleicher A, Zilles K (1999) Areas 3a, 3b, and 1 of human primary somatosensory cortex. Neuroimage 10:63–83.[CrossRef][Web of Science][Medline]

Hoechstetter K, Rupp A, Stancak A, Meinck HM, Stippich C, Berg P, Scherg M (2001) Interaction of tactile input in the human primary and secondary somatosensory cortex — a magnetoencephalographic study. Neuroimage 14:759–767.[CrossRef][Web of Science][Medline]

Hsieh CL, Shima F, Tobimatsu S, Sun SJ, Kato M (1995) The interaction of the somatosensory evoked potentials to simultaneous finger stimuli in the human central nervous system. A study using direct recordings. Electroencephalogr Clin Neurophysiol 96:135–142.[CrossRef][Medline]

Ishibashi H, Tobimatsu S, Shigeto H, Morioka T, Yamamoto T, Fukui M (2000) Differential interaction of somatosensory inputs in the human primary sensory cortex: a magnetoencephalographic study. Clin Neurophysiol 111:1095–1102.[CrossRef][Web of Science][Medline]

Iwamura Y (1998) Hierarchical somatosensory processing. Curr Opin Neurobiol 8:522–528.[CrossRef][Web of Science][Medline]

Iwamura Y, Tanaka M, Hikosaka O (1980) Overlapping representation of fingers in the somatosensory cortex (area 2) of the conscious monkey. Brain Res 197:516–520.[CrossRef][Web of Science][Medline]

Iwamura Y, Tanaka M, Sakamoto M, Hikosaka O (1983a) Converging patterns of finger representation and complex response properties of neurons in area 1 of the first somatosensory cortex of the conscious monkey. Exp Brain Res 51:327–337.[Web of Science]

Iwamura Y, Tanaka M, Sakamoto M, Hikosaka O (1983b) Functional subdivisions representing different finger regions in area 3 of the first somatosensory cortex of the conscious monkey. Exp Brain Res 51:315–326.[Web of Science]

Iwamura Y, Tanaka M, Sakamoto M, Hikosaka O (1993) Rostrocaudal gradients in the neuronal receptive field complexity in the finger region of the alert monkey's postcentral gyrus. Exp Brain Res 92:360–368.[Web of Science][Medline]

Kaas JH (1983) What, if anything, is SI? Organization of first somatosensory area of cortex. Physiol Rev 63:206–231.[Free Full Text]

Kaas JH, Nelson RJ, Sur M, Lin CS, Merzenich MM (1979) Multiple representations of the body within the primary somatosensory cortex of primates. Science 204:521–523.[Abstract/Free Full Text]

Krause T, Kurth R, Ruben J, Schwiemann J, Villringer K, Deuchert M, Moosmann M, Brandt S, Wolf K, Curio G, Villringer A (2001) Representational overlap of adjacent fingers in multiple areas of human primary somatosensory cortex depends on electrical stimulus intensity: an fMRI study. Brain Res 899:36–46.[CrossRef][Web of Science][Medline]

Kurth R, Villringer K, Mackert BM, Schwiemann J, Braun J, Curio G, Villringer A, Wolf KJ (1998) fMRI assessment of somatotopy in human Brodmann area 3b by electrical finger stimulation. Neuroreport 9:207–212.[Web of Science][Medline]

Kurth R, Villringer K, Curio G, Wolf KJ, Krause T, Repenthin J, Schwiemann J, Deuchert M, Villringer A (2000) fMRI shows multiple somatotopic digit representations in human primary somatosensory cortex. Neuroreport 11:1487–1491.[Web of Science][Medline]

Kwong KK, Belliveau JW, Chesler DA, Goldberg IE, Weisskoff RM, Poncelet BP, Kennedy DN, Hoppel BE, Cohen MS, Turner R, Cheng HM, Brady TJ, Rosen BR (1992) Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation. Proc Natl Acad Sci USA 89:5675–5679.[Abstract/Free Full Text]

Lauritzen M (2001) Relationship of spikes, synaptic activity, and local changes of cerebral blood flow. J Cereb Blood Flow Metab 21:1367–1383.[CrossRef][Web of Science][Medline]

Lauritzen M, Gold L (2003) Brain function and neurophysiological correlates of signals used in functional neuroimaging. J Neurosci 23:3972–3980.[Free Full Text]

Lin W, Kuppusamy K, Haacke EM, Burton H (1996) Functional MRI in human somatosensory cortex activated by touching textured surfaces. J Magn Reson Imaging 6:565–572.[Web of Science][Medline]

Macgillis M, Kang R, Herman D, Zarzecki P (1983) Interactions among convergent inputs to somatosensory cortex neurons. Brain Res 276:329–332.[CrossRef][Web of Science][Medline]

Maldjian JA, Gottschalk A, Patel RS, Detre JA, Alsop DC (1999) The sensory somatotopic map of the human hand demonstrated at 4 Tesla. Neuroimage 10:55–62.[CrossRef][Web of Science][Medline]

Mathiesen C, Caesar K, Akgoren N, Lauritzen M (1998) Modification of activity-dependent increases of cerebral blood flow by excitatory synaptic activity and spikes in rat cerebellar cortex. J Physiol 512:555–566.[Abstract/Free Full Text]

Merzenich MM, Kaas JH, Sur M, Lin CS (1978) Double representation of the body surface within cytoarchitectonic areas 3b and 1 in ‘SI’ in the owl monkey (Aotus trivirgatus). J Comp Neurol 181:41–73.[CrossRef][Web of Science][Medline]

Mirabella G, Battiston S, Diamond ME (2001) Integration of multiple-whisker inputs in rat somatosensory cortex. Cereb Cortex 11:164–170.[Abstract/Free Full Text]

Moore CI, Stern CE, Corkin S, Fischl B, Gray AC, Rosen BR, Dale AM (2000) Segregation of somatosensory activation in the human rolandic cortex using fMRI. J Neurophysiol 84:558–569.[Abstract/Free Full Text]

Nelson RJ, Sur M, Felleman DJ, Kaas JH (1980) Representations of the body surface in postcentral parietal cortex of Macaca fascicularis. J Comp Neurol 192:611–643.[CrossRef][Web of Science][Medline]

Ogawa S, Tank DW, Menon R, Ellermann JM, Kim SG, Merkle H, Ugurbil K (1992) Intrinsic signal changes accompanying sensory stimulation:functional brain mapping with magnetic resonance imaging. Proc Natl Acad Sci USA 89:5951–5955.[Abstract/Free Full Text]

Penfield W, Boldrey E (1937) Somatic motor and sensory representation in the cerebral cortex of man as studied by electrical stimulation. Brain 60:389–443.[Free Full Text]

Pons TP, Garraghty PE, Cusick CG, Kaas JH (1985) The somatotopic organization of area 2 in macaque monkeys. J Comp Neurol 241:445–466.[CrossRef][Web of Science][Medline]

Ritter P, Villringer A (2002) Inhibition and functional magnetic resonance imaging. In: Brain activation and CBF control (Tomita M, Kanni I, Hamel E, eds), pp. 213–222. Amsterdam: Elsevier.

Ruben J, Schwiemann J, Deuchert M, Meyer R, Krause T, Curio G, Villringer K, Kurth R, Villringer A (2001) Somatotopic organization of human secondary somatosensory cortex. Cereb Cortex 11:463–473.[Abstract/Free Full Text]

Servos P, Zacks J, Rumelhart DE, Glover GH (1998) Somatotopy of the human arm using fMRI. Neuroreport 9:605–609.[Web of Science][Medline]

Vogt C, Vogt O (1919) Allgemeinere Ergebnisse unserer Hirnforschung. J Psychol Neurol 25:279–462.


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