Source activity in the human secondary somatosensory cortex depends on the size of corpus callosum

Brain Research 936 (2002) 47–57www.elsevier.com/ locate /bres

Research report

Source activity in the human secondary somatosensory cortex dependson the size of corpus callosum

a , b c a a*Andrej Stancak , Karsten Hoechstetter , Jaroslav Tintera , Jiri Vrana , Rosa Rachmanova ,a bJiri Kralik , Michael Scherg

aDepartment of Normal, Pathological and Clinical Physiology, Third Faculty of Medicine, Charles University Prague, Ke Karlovu 4,120 00 Prague 2, Czech Republic

bSection of Biomagnetism, Department of Neurology, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, GermanycInstitute of Clinical and Experimental Medicine, Videnska 800, 140 00 Prague 4, Czech Republic

Accepted 6 February 2002

Abstract

If corpus callosum (CC) mediates the activation of the secondary somatosensory area (SII) ipsilateral to the side of stimulation, thenthe peak latencies of the contra- and ipsilateral SII activity as well as the amplitude of the ipsilateral SII activity should correlate with thesize of CC. Innocuous electrical stimuli of five different intensities were applied to the ventral surface of the right index finger in 15right-handed men. EEG was recorded using 82 closely spaced electrodes. The size of CC and of seven callosal regions was measuredfrom the mid-sagittal slice of a high-resolution anatomical MRI. The activation in the contralateral and ipsilateral SII was evaluated usingspatio-temporal source analysis. At the strongest stimulus intensity, the size of the intermediate part of the callosal truncus correlatednegatively with the interpeak latency of the sources in ipsi- and contralateral SII (r520.83, P,0.01). Stepwise regression analysisshowed that the large size of the intermediate truncus of CC was paralleled by a latency reduction of peak activity of the ipsilateral SII,whereas both contra- and ipsilateral peak latencies were positively correlated. The peak amplitude of the ipsilateral SII source correlatedpositively with the size of the intermediate truncus of CC, and with the peak amplitudes of sources in the primary somatosensory cortex(SI) and in the mesial frontal cortex. The results suggest that in right-handed neurologically normal men, the size of the intermediatecallosal truncus contributes to the timing and amplitude of ipsilateral SII source activity. 2002 Elsevier Science B.V. All rightsreserved.

Theme: Somatosensory and visceral afferents

Topic: Somatosensory cortex and thalamocortical relationships

Keywords: Secondary somatosensory area; Corpus callosum; EEG; Dipole source analysis

1. Introduction magnetoencephalography (MEG) or electroencephalog-raphy (EEG). The neuromagnetic fields generated from the

The secondary somatosensory area is a small cortical contralateral SII show peak latencies from 80 to 100 ms2area sized about 2 cm and located in the upper bank of the [19,20,27,28,62]. The magnetic response in the ipsilateral

Sylvian fissure [36,43,65]. Brief, phasic stimuli such as SII follows the contralateral peak with a delay of |15 mselectrical stimulation of the median nerve [18– [27,28,62]. However, a large inter-individual variance in20,26,27,41], air puff stimuli [19], tactile pressure pulses the time delay of the ipsilateral relative to the contralateral[28,29], and painful laser heat [10,23,37,61] or electrical SII source peaks has been noted [62]. The latency of thestimuli [60] evoke specific neuromagnetic fields and SII peak response in EEG recordings ranges from 100 toelectrical potentials in SII which can be studied using 150 ms [24,60]. Since the late SII component (.100 ms)

has rarely been observed in MEG studies, radial orienta-tion of the underlying source activity can be suspected. A*Corresponding author. Tel.: 1420-2-2492-3241; fax: 1442-2-2492-radial source in SII around 100–120 ms has been con-3905.

E-mail address: [email protected] (A. Stancak). firmed in intracortical recordings [6,7,22,23].

0006-8993/02/$ – see front matter 2002 Elsevier Science B.V. All rights reserved.PI I : S0006-8993( 02 )02502-7

48 A. Stancak et al. / Brain Research 936 (2002) 47 –57

The bilateral activation of SII areas following unilateral their right hand resting on a platform. Surface electro-somatosensory stimuli and the time delay of the ipsilateral cutaneous stimulation of the index finger was used in theSII response relative to the contralateral SII activation present study to avoid overlap with long-latency motorsuggest that the ipsilateral SII response might be related to evoked potentials elicited by median nerve stimulation.the transcallosal connections of both SII areas. The trans- The electrical stimuli were applied to the ventral surface ofcallosal fibers connecting both SII areas are relatively the right index finger using two silver cup electrodes filleddense [31,44–46]. Subjects with callosal transection show with electrode gel (Elefix, Nihon-Kohden Corp., Tokyo,activation in response to a unilateral hand stimulation in Japan). The distal electrode (anode) was placed 0.5 cmthe contralateral but not in the ipsilateral SII [17]. Besides from the tip of the finger. The proximal electrode (cathode)homotopic callosal projections, heterotopic connections was placed on the second phalanx. The electrode to skinbetween SII and SI of the opposite hemisphere have been impedance was always below 10 kV. The duration of thereported [31,35,38,39]. However, some ipsilateral SII monophasic constant current stimulus was 0.1 ms. In theactivation was observed even after callosotomy in mon- beginning of recording, the sensory threshold was de-keys [46] suggesting additional extracallosal input to termined by applying the cutaneous stimuli in steps ofipsilateral SII. 0.1–0.2 mA in ascending and descending directions. We

The intermediate part of CC contains predominantly then determined the highest stimulus intensity which thefibers of large diameter (.3 mm) [3]. The size of a subjects indicated as painful or very unpleasant. The painparticular callosal region is determined by the fibers sensation was described as a prick or a hit with a solidcomposing that region [2]. It can be conjectured that a object. Some of the subjects hesitated to use pain terms butlarge number of thick axons may facilitate the speed and indicated the intensity which they felt as very unpleasant.temporal summation of neuronal impulses transmitted from Using individual sensory and pain /unpleasantness thres-the contra- to ipsilateral SII. In this study, somatosensory holds, five stimulus intensities were computed according toevoked potentials were analyzed using spatio-temporal the formula:source analysis [48,49] to evaluate the dynamics of the

stimulus intensity5d 3(unpleasantness2sensory threshold)ipsilateral and contralateral SII response to the innocuous1sensory threshold (1)electrocutaneous stimuli, and in vivo magnetic resonance

imaging to measure the size of CC. We postulated that ifwhere d corresponded to one of five values: 0.20, 0.35,CC plays a role in activation of the ipsilateral SII, then the0.50, 0.65 and 0.80. This procedure ensured that even thestrength of the ipsilateral SII source and the time delay ofweak stimuli (d 5 0.20) were felt throughout the wholethe ipsilateral relative to the contralateral SII peak wouldsession in spite of the effects of habituation, and that thebe a function of the callosal size, especially of the callosalstrong stimuli (d 5 0.80) were below the pain threshold.body which is known to connect the sensorimotor areas

Five blocks of 130 stimuli interspersed with 5 min[44,45]. The activation of SII is related to stimulusresting periods were presented during the experiment. Theintensity [33,29,42]. Thus, we employed five stimulusduration of each block was about 22 min. In each block,intensities which covered a wide range of non-painfultwenty-six stimuli of each intensity were presented insensations and analyzed the correlations between therandom inter-stimulus intervals ranging from 6 to 12 s.callosal parameters and the source activities of contralater-The order of the stimuli was also randomized. Theal and ipsilateral SII at each stimulus intensity.subjective intensity was recorded using the visual analoguescale (VAS) after each of the five blocks of stimuli andprior to the first block. The VAS scale was a 100 mm2. Methodshorizontal line representing the continuum of subjectiveintensities ranging from ‘just perceived’ to ‘already pain-2.1. Subjectsful’. For statistical analysis, the individual mean valuescomputed from all six VAS presentations were used.Fifteen healthy men aged 22.162.4 (mean6standard

deviation) participated in the study. The use of men in ourstudy was justified by sex differences in the size [4,53] and 2.1.2. Recordingsfiber composition [3] of CC. All subjects were right- EEG was recorded using 82 Ag/AgCl (EEGCapings,handed according to the Hand-Dominanz Test [51]. The Graz, Austria) electrodes in continuous mode on Brain-subjects gave their written consent prior to the experiment Scope equipment (M&I, Prague, Czech Republic). Theaccording to the declaration of Helsinki. The experimental electrodes covered the frontal, central, temporal and pariet-procedure was approved by the Ethical Committee of the al areas of both hemispheres with an average inter-elec-

´ ´Hospital Kralovske Vinohrady in Prague. trode distance of 2.5 cm. The electrode to skin impedancewas kept below 5 kV. The reference electrode was

2.1.1. Procedure mounted on the forehead. The diagonal electrooculogramThe subjects were seated in a comfortable armchair with was recorded bipolarly by placing one electrode above the

A. Stancak et al. / Brain Research 936 (2002) 47 –57 49

eyebrow and the other to the lateral corner of the eye. EEG stimulus) after band-pass filtering (1 Hz, 6dB/octave–50was recorded using a sampling frequency of 1024 Hz and a Hz, 24dB/octave) and analyzed using the Brain Electricalbandpass filter of 0.015–200 Hz. The 3-D electrode Source Analysis (BESA) program (MEGIS Software,coordinates and about fifty surface points describing the Munich, Germany). An ellipsoidal, four-shell conductorhead contour were measured at the end of each experiment head model was employed. A source model of the EEGusing an Isotrak II digitizer (Polhemus Inc., Colchester, potentials was constructed from the grand average dataVermont, USA). (N515) (Fig. 2A) using the grand average of electrode

Structural MRI data of the whole brain were acquired on positions and head diameters. To match the source loca-a 1.5-Tesla Magnetom Vision (Siemens, Erlangen, Ger- tions to the individual brain anatomy, BrainVoyagermany) using a volume encoded, fast-low-angle-shot pulse (BrainInnovation B.V., Maastricht, Netherlands) was used.sequence with parameters TR/TE/a525 ms/6 ms/208. The fiducial surface points and the 3-D electrode positions

2The field of view was set to 2563256 mm , the matrix were fitted to the skin surface to enable a coregistration ofsize to 2563256 pixels and the slab of 180 mm thickness the EEG sources to the 3-D brain images. The MRI datawas divided into 180 partitions resulting in an isotropic were transformed into the Talairach coordinate system [56]

3voxel size of 1 mm . The mid-sagittal slice yielding a clear and the Talairach coordinates of the EEG sources wereview of fornix and anterior commissure was selected andthe contrast was enhanced using the Paintshop5 program(JASC, Eden Prairie, Minnesota, USA). The CC wasextracted using a magic wand procedure of the sameprogram and the total cross-sectional area of CC as well asthe areas of its seven regions (Fig. 1) were measured[53,63]. The division of CC into seven regions roughlycorresponds to the rostrum, genu, rostral truncus, anteriorintermediate truncus, posterior intermediate truncus, isth-mus and splenium of the CC [63].

2.1.3. Data analysisFor averaging, data epochs of 768-points with a total

length of 0.75 s (0.25 s prestimulus and 0.5 s poststimulustime) were selected. Trials containing EMG artefacts orlarge EOG variations (.150 mV) were discarded fromfurther analysis. Averaged EEG epochs were segmented toa total length of 400 ms (50 ms pre- to 350 ms post-

Fig. 2. (A) Locations, orientations (left panel) and source waveforms (x,Fig. 1. Evaluation of the callosal parameters according to Witelson [63]. y, and z components) of the four regional sources sources (right panel)ACC and PCC correspond to the anteriormost and posteriormost border derived from the grand average data. The largest of the three orthogonalof corpus callosum (CC), respectively, and define the length of the CC. components is always denoted as x. The left panel shows the locations ofPoint G represents the anteriormost point of the inner convexity of the the regional sources (15SI, 25SIIc, 35SIIi, 45SMA) in the lateral, topanterior CC. The line perpendicular to the ACC–PCC line which crosses and frontal views. The short lines originating in each square depict thethe point G defines regions 1 and 2. Regions 3–7 are delineated by the orientation of the primary component of the respective regional source.vertical lines corresponding to the halves, thirds and fifths of the ACC– The filled squares and the lengths of the orientation lines illustrate thePCC line. The seven regions roughly correspond to the rostrum (1), genu source strengths at a latency of 130 ms for SIIc, SIIi and SMA sources,(2), rostral truncus (3), anterior intermediate truncus (4), posterior and at 45 ms for SI. (B) Three-dimensional localization of the EEGintermediate truncus (5), isthmus (6) and splenium (7) of the CC. sources in one subject.


evaluated for each subject. The source model developed 3.1. Source modelfrom the grand average data was used to evaluate thedipole source waveforms in the individual recordings. The Using a sequential strategy, four regional sourcesorientation of the primary component of each of the [48,49] were fitted to describe the 3-dimensional sourceregional sources was determined from the individual currents in the four regions contributing predominantly toaverage data (average waveforms from five recordings the data (Fig. 2A and B). Regional source 1 was fitted incorresponding to five stimulus intensities) at the respective the time interval from 20 to 55 ms. The orientation of themaxima of the source waveforms. The root mean square of primary of the three orthogonal components was deter-the three orthogonal components of each regional source mined at the maximum of the source strength in thewas computed and the peak latencies and amplitudes were selected time interval. Source 1 localized to the contralater-measured for each stimulus intensity. al primary sensorimotor area and it is referred to as the SI

source. The orientation of the primary component of thisregional source was tangential and pointed posteriorly

2.1.4. Statistical analysissimilar to the source of the P30 wave of the somatosensory

Dipole source moment was evaluated as the root meanevoked potential of area 3b [5]. Three additional regional

squared sum of the three orthogonal components (x, y andsources could be fitted in the time interval from 100 to 150

z) of each regional source. To approximate a Gaussianms. Regional source 2 peaked around 128 ms and localized

distribution, the decadic logarithm of the root mean squareto the contralateral hemisphere in the vicinity of the lateral

values was used in the statistical analyses. The effects ofcerebral fissure. The orientation of the primary orthogonal

stimulus intensity on the dipole source moments wascomponent of the 2nd regional source was close to radial

analyzed using analysis of variance (ANOVA) for repeated(Fig. 2A). The location, orientation and latency suggested

measures. The independent variables were stimulus in-that source 2 corresponded to the activation of the con-

tensity (five levels) and hemisphere (SIIc vs. SIIi). Totralateral SII area. The 3rd regional source fitted to the

overcome a violation of the sphericity assumption due tocorresponding location in the ipsilateral, right hemisphere

repeated measures, the Greenhouse–Geisser epsilon cor-with a peak latency of 147 ms. The orientation of the

rection of degrees of freedom was used. The associationprimary component of this regional source was also

between the size of each of seven callosal regions and ofpredominantly radial. The location of source 3 and the 19

the total CC with peak amplitudes of SIIc and SIIi sourcesms delay of its peak relative to the SIIc peak suggested

and with the SIIi–SIIc peak latency difference was ana-origin in the ipsilateral SII. Hence, sources 2 and 3 are

lyzed using the Pearson product–moment correlations [9].further denoted as SIIc and SIIi sources, respectively.

Each correlation was tested for the presence of extremeFitting the data using three sources (SI, SIIc and SIIi) over

values using the k1 statistics of Dixon [16]. Stepwisethe whole epoch at this step showed that both SII sources

regression analysis (NCSS program, Kaysville, Utah,tended to move towards midline and frontal areas. Inspec-

USA) was computed to evaluate the contribution of a set oftion of the residual potential waveforms revealed un-

independent variables to a selected independent variable. Aexplained negativity over the vertex peaking from 130 to

95% confidence level was used throughout.140 ms. Thus, a 4th regional source had to be incorporatedinto the model to obtain a stable localization of the SIIsources bilaterally. The tangentially oriented source 4 fitted

3. Results to the mesial frontal cortex and showed a peak latency ofabout 136 ms. Due to the anatomical location it is referred

The mean individually adjusted stimulus intensities were to hereafter as the supplementary-motor-area (SMA)5.661.4 mA, 7.362.0 mA, 8.962.6 mA, 10.663.3 mA source. The model was further improved by adding oneand 12.363.9 mA for the five intensity levels, respectively. spatial principal component [8,48] to remove slow drifts inThe five stimulus intensities differed significantly from the EEG data. In order to separate alpha rhythmic activityeach other according to the ANOVA for repeated measures in individual subjects, one regional source was placed into(F(4,56)585.2, P,0.0001). The mean sensory threshold the midline parieto-occipital area (unit sphere coordinates:in our subjects was 3.361.0 mA. Thus, the weakest and x 5 0.0, y 5 0.42, z 5 0.54). Incorporation of the alphathe strongest stimulus intensities were 1.7 times and 3.7 source improved the readings of the source waveforms oftimes stronger than the sensory threshold, respectively. The SI and SII in individual recordings, especially at lowpain /unpleasantness threshold was 14.864.8 mA, and the stimulus intensity (d 50.20).lowest and highest individual values were 9.9 mA and 26.7mA, respectively. The VAS intensity scores showed a 3.2. SI sourcelinear increase paralleling the current intensity (F(4,56)5

72.3, P,0.0001). The mean VAS values for the five Fig. 2B shows the 3-D localizations of the four regionalintensity levels were 8.968.3, 20.6613.2, 36.4615.4, sources in one subject. The individual and grand average53.1618.3 and 69.8622.8, respectively. source waveforms are presented in Fig. 3A and B, respec-


Fig. 3. (A) Individual root mean square source waveforms in subject S04. The waveforms represent the root mean squared sum of the x, y and z orthogonalcomponents of the respective regional source (SI, SIIc, SIIi, SMA). The rows correspond to different stimulus intensities ranging from weak (d 5 0.2) tostrong (d 5 0.8). (B) Grand average source dipole moments of the four regional sources (SI, SIIc, SIIi, SMA). Average taken over all subjects. The thinlines around the mean waveforms correspond to the 95% confidence interval.

tively. The peak latency of the SI source was 45.3610.2 longer than 20 ms attributed to the precentral cortex [40],ms. The peak latency indicates a lack of a clear P30 or due to both factors. Peak amplitude of the SI source wascomponent which is consistent with a small P30 com- significantly influenced by stimulus intensity (F(4,56)5

ponent and absence of a clear polarity reversal over the 10.3, P,0.0001). The effect of stimulus intensity on SIfrontal and parietal scalp electrodes during electrical peak latency was not significant (F(4,56)50.3, P.0.05).stimulation of digits compared to median nerve stimulation[47]. The localization of the SI source (Talairach coordi- 3.3. SII sourcesnates (mean6SEM) x5237.361.3, y5217.061.7, z5

52.16 0.8 mm) was in the anterior bank of the central The SII sources were located in the upper bank of thesulcus rather than in the posterior bank as would be Sylvian fissure (Fig. 2A and B), and the Talairach coordi-expected from the location of the Brodmann area 3b [5]. nates of the SII sources (SIIc: x 5 2 49.760.8, y 5

The slightly anterior location of the SI source might be due 2 10.860.6, z 5 18.463.2 mm; SIIi: x 5 49.960.8, y 5

to localization errors of the spherical head model known to 2 9.161.2, z 5 24.761.0 mm) were consistent with previ-be in the order of 10–11 mm in EEG recordings [13,14], ous studies [23,28]. Fig. 3A and B illustrates the root meanor due to the contribution of a radial source with latency square source waveforms of the SIIc and SIIi for each


stimulus intensity. Analysis of variance for repeated mea- significant regression coefficients in the stepwise dis-sures using five intensities and hemisphere as independent criminant analysis (Table 1A). However, the relativevariables revealed a significant effect of hemisphere increments of the standardized regression coefficients for(F(1,14)55.3, P50.04) and stimulus intensity (F(4,56)5 these callosal region were small compared to the peak16.7, P,0.0001). In addition, we found a significant latency of SIIc source and the size of callosal region 4.interaction between stimulus intensity and hemisphere Stepwise discriminant analysis with the peak amplitude(F(4,56)54.3, P50.008). The test of simple effects of SIIi as dependent variable (Table 1B) showed positiveshowed that the interaction was due to the significantly relationships with the peak amplitude of the SI and SMAlarger amplitude of SIIc as compared to SIIi under low and sources, and with the size of the callosal region 4, and amedium stimulus intensities (d 5 0.20, F(1,14)58.6, P5 negative relationship with the size of callosal region 7. The0.01; d 5 0.35, F(1,14)59.8, P50.007; d 5 0.5, regression coefficient of the SIIc peak amplitude was notF(1,14)55.8, P50.03) but not under two strong stimulus significant (P.0.05). The relationship between the peakintensities (d 5 0.65, F(1,14)53.3, P50.09; d 50.80, amplitude of the SIIi and SIIc sources and the size ofF(1,14)50.6, P50.56). callosal region 4 is illustrated in Fig. 4B.

The mean peak latencies of SIIc and SIIi sources were As far as the contralateral SII peak amplitude is128.8616.6 ms, and 146616.6 ms, respectively. Thus, the concerned, stepwise regression analysis with this am-SIIi peak followed the SIIc peak with mean latency of plitude as a dependent variable revealed that only the peak17.4611.4 ms. The SIIi–SIIc peak latency differences amplitude of the SI source contributed to SIIc peakranged from 0 to 34 ms indicating a large inter-individual amplitude (standardized regression coefficient 0.65, T5

variability. The two-way ANOVA for repeated measures 3.08, P,0.009). The pair-wise correlation coefficientusing stimulus intensity and hemisphere as independent between the peak amplitudes of SI and SIIc sources wasvariables showed a significant difference between the r(14)50.57, P50.02. The peak latency of SIIc correlatedcontra- and ipsilateral SII peak latency (F(1,14)592.6, significantly with the peak latency of SIIi (Table 1A) butP,0.0001). The effect of stimulus intensity on the peak not with the peak latency of the SI response (r(14)5

latencies of the SIIc and SIIi sources was not significant 20.15, P50.61).(P.0.05).

3.5. The mesio-frontal source3.4. Corpus callosum and SIIi

Source analysis revealed an additional source in thePearson product–moment correlations were computed mesial frontal cortex (Fig. 2A and B) peaking at

between the SIIi–SIIc peak latency difference and the 135.8616.1 ms (Fig. 3A and B), i.e. intermediate betweencallosal parameters for each stimulus intensity. A signifi- SIIc and SIIi peak latencies. The Talairach coordinatescant negative correlation was observed between the size of (x 5 2 1.561.2, y 5 2 0.162.1, z 5 63.360.8 mm)region 4 and the SIIi–SIIc peak latency difference for the pointed to SMA as the generator area. The effects of thestrongest stimulus intensity (d 5 0.80, r(14) 5 2 0.83, P, stimulus intensity on the SMA source were significant0.001) (Fig. 4A) but not for other stimulus intensities (F(4,56)510.8, P50.0005) according to the ANOVA for(P.0.05). To analyze which of the callosal and source repeated measures. The peak latency of the SMA sourceparameters correlated with SIIi peak latency, a stepwise was not influenced by stimulus intensity (P.0.05).regression analysis was performed using the peak latencyof the SIIi source as dependent variable and the peaklatencies of the SIIc, SI and SMA sources, and the callosal 4. Discussionparameters as independent variables. Since significant pair-wise correlation coefficients between source and callosal The involvement of the callosal fiber system in theparameters occurred only for the strongest stimulus intensi- activation of the ipsilateral SII can be inferred from thety, the stepwise regression analysis was performed for the connectivity studies in non-human primatesstrong stimulus (d 5 0.8). The results of this analysis in the [31,35,38,39,46], and from the absence of ipsilateral SIIform of standardized regression coefficients, the increment activation in patients with callosotomy [17]. Using EEGof the squared regression coefficient representing the source imaging and MRI recordings in neurologicallyimportance of each regression coefficient, T-statistics and healthy subjects, our data show for the first time that theprobability levels for SIIi peak latency and amplitude are size of corpus callosum contributes to the peak amplitudegiven in Table 1A and B. The peak latency of the SIIc of the ipsilateral SII activation and to the time delaysource and the size of region 4 showed significant stan- between the ipsilateral and contralateral SII peaks.dardized regression coefficients with SIIi peak latency. Thelonger the peak latency of the SIIc source and the smaller 4.1. Source modelthe region 4, the greater was the SIIi peak latency. Besidesregion 4, the sizes of callosal regions 2, 5 and 7 showed The source model used in the present study yielded four


Fig. 4. (A) Relationship between the size of callosal region 4 and the peak latency difference of the ipsi- and contralateral SII responses (SIIi–SIIc) at thestrongest stimulus intensity (d 5 0.8). The waveforms of the primary component of the SIIc (bold line) and SIIi (thin line) regional sources in subjectshaving a small (S01) and a large (S12) region 4 of CC. The right panel shows the scatter-plot of individual values and the linear regression line illustratingthe negative correlation between the size of region 4 (x-axis) and the interhemispheric peak latency difference SIIi–SIIc ( y-axis). (B) Relationship betweenthe size of callosal region 4 and the peak amplitude of SIIi and SIIc sources at the strongest stimulus intensity (d 5 0.8). The SIIc (left upper panel) andSIIi (left lower panel) root mean square source waveforms in three subjects having small (dotted line), medium (thin solid line) and large (bold line) region4 of corpus callosum are shown. MRI segments of individual corpora callosa are illustrated in the middle part of the figure. The scatter-plot of individualvalues illustrating the significant correlation coefficient between the size of region 4 and the peak amplitude of the SIIi source is shown in the right lowerpanel. The correlation coefficient between the peak amplitude of SIIc source and region 4 was not statistically significant (right upper panel).

interpretable cortical sources. The sources in SI, SIIc and stimuli (d 50.20, 0.35 and 0.50), the strength of theSIIi are consistent with source models used in previous contralateral SII source was greater than the strength of theMEG [27,28,41,62] and EEG studies [60,61]. One distinc- ipsilateral SII source consistent with previous MEG studiestion from the MEG studies was the longer latency and [28,33,42]. For the strong stimuli (d 50.65 and 0.80), SIIcprevailing radial orientation of the SII sources. A radial and SIIi activations showed about equal strength. Com-source with a peak latency .100 ms [5,22,23] and the parison with other studies is difficult since they might notunequal habituation of various SII components [6] may have covered a sufficient range of intensities. It is possibleaccount for this discrepancy. The SMA source in our that the intensity of the strong pressure pulse stimulus in amodel is fully consistent with localization of the N130 previous study [28] did not exceed the equivalent of thecomponent in intracortical recordings [6,7] and with PET medium stimulus intensity of the present study. Theand fMRI studies reporting activation of SMA following median nerve stimuli in previous studies elicited a fingerinnocuous somatosensory stimulation [15,50,57]. movement [33,42] which might diminish the SII response

to the somatosensory stimulus by gating the long-latency4.2. Stimulus intensity and SII activation neuromagnetic fields. In support of this explanation, the

SII source amplitudes in both hemispheres were equal forThe activity of all four EEG sources increased in strong (twice the motor threshold) and medium stimuli

parallel with stimulus intensity. For the weak and medium (just above the motor threshold) [33].


Table 1

Dependent Standardized Increment of T-value Probabilityvariable: SIIi regression the standardized level

coefficient regressioncoefficient

A. Stepwise regression and analysis for the peak latency of the SIIi sourceSIIc peak latency 0.862 0.69 19.38 0.0001CC region 4 20.704 0.29 212.4 0.000CC region 2 20.174 0.02 23.16 0.011CC region 5 0.242 0.03 3.94 0.003CC region 7 0.173 0.02 3.32 0.009SI peak latency 0.49 n.s.SMA peak latency 0.32 n.s.CC region 1 1.80 n.s.CC region 3 1.39 n.s.CC region 6 1.41 n.s.Total CC area 1.32 n.s.

B. Stepwise regression analysis for the SIIi peak amplitudeSI amplitude 0.520 0.17 4.53 0.001SMA amplitude 0.552 0.24 5.34 0.0001CC region 4 0.322 0.08 3.02 0.012CC region 7 20.388 0.11 23.56 0.005SIIc amplitude 0.09 n.s.CC region 1 0.49 n.s.CC region 2 0.14 n.s.CC region 3 0.22 n.s.CC region 5 1.49 n.s.CC region 6 0.68 n.s.Total CC area 0.14 n.s.

4.3. Corpus callosum and SII ening of the callosal transmission time between both SIIareas. In men, the size of the intermediate truncus corre-

The peak latency of the ipsilateral SII source follows the lates with the size of the Sylvian fissure and planumpeak response of the contralateral SII source in neuro- temporale [1]. A hemispheric assymetry of the horizontalmagnetic and EEG recordings with a time delay of about ramus of the Sylvian fissure has also been reported [52,64].10–20 ms which corresponds to the transmission time Although the correlations between callosal parameters andfrom the contra- to the ipsilateral SII as estimated in source activation in the ipsilateral SII may also be associ-previous studies [10,22]. However, the individual vari- ated with structural differences in the left and right SII, theability in the peak latency was large both in the present impact of these hemispheric asymmetries, e.g. in the shapeand previous studies [28,62]. We even found a simulta- of the Sylvian fissure [52,64] cannot account for individualneous onset of the ipsi- and the contralateral SII peak in differences in the interpeak latency of SII sources in theone subject. range of tens of milliseconds.

The significant correlation between the peak latency According to the velocities of neuronal transmission indifference of ipsi- and contralateral SII responses and the callosal fibers [1,55] and the estimated 0.1 m distancesize of region 4 and the stepwise regression analysis between the right and left SII, the shortest possible peaksupport the view that CC contributes to the timing of the difference between the left and right SII in subjects withipsilateral SII response. Our finding of a positive correla- large-diameter callosal fibers (.4.7 mm) would be 1.5 mstion between the size of callosal region 4 and the peak [1]. On the other hand, considering a prevalence of small-latency of the ipsilateral SII activation fits with electro- diameter fibers (|0.4 mm) in subjects with the smallestphysiological studies demonstrating that the intermediate size of callosal truncus, the estimated inter-hemisphericpart of CC contains the callosal fibers connecting the transmission would be .20 ms. [1]. Additional delaysensorimotor areas of both hemispheres [44,45]. It is might arise from the interaction of the callosal andespecially this intermediate truncus of CC which contains extracallosal inputs in the ipsilateral SII. In subjects havinglarge-diameter fibers (.3 mm) [3]. Furthermore, the size a large callosal midbody, various inputs might act inof a particular callosal area correlates with the number of concert to provide a superior functional control of thethose fibers which constitute that callosal area [2]. Thus, ipsilateral SII area.we suggest that a large midbody of CC has an abundance The SIIi peak amplitude was mostly influenced by theof the large-diameter fibers which contribute to the short- peak amplitudes of the SI and the mesial frontal sources


and by the size of the callosal region 4. The positive healthy subjects appear to dominate and contribute both tocorrelations between SIIi peak amplitude and both the SI the amplitude and timing of the ipsilateral SII sourcepeak amplitude and the size of callosal region 4 may be activation.related to the heterotopic callosal connections between SII Significant correlations between the callosal parametersand SI of the opposite hemisphere which have been and the dipole source moments were only observed for thedemonstrated in non-human primates [31,35,38,39]. SI strongest (d 5 0.8) stimuli. The ipsilateral SII sourceexerts a facilitatory influence upon both SII areas consist- showed an amplitude equal to that of the contralateral SIIing of adjustment of the background excitation of SII source only under the two strongest stimulus intensitiesneurons [11,12,58,59,66]. An activation in SII paralleling suggesting that the manifestation of the callosal influencesthe SI activation has been observed in one neuromagnetic depends on sufficient neuronal input to the ipsilateral SII.study in the early post-stimulus period [34]. Fig. 3A and Bof the present study and previous intracortical [7] andMEG [21] recordings showed that SI remains active for at Acknowledgementsleast 150 ms period after stimulus onset. Since a modula-tion of the ipsilateral SII activity from the contralateral SI This study was supported by the Grant Agency of theis mediated by the transcallosal fibers, the size of the Czech Republic (309/98/1065 and 309/01/0665), IGAcallosal midbody is the limiting factor of the SI influence (NF 6377-3 /2000), Research Directions of the Czechupon the ipsilateral SII. If the callosal midbody is large, Republic (JS 0011112006) and a fellowship from the Landthe sum of the influences from the contralateral SI and SII ¨Baden-Wurtemberg to Dr. Stancak. K. Hoechstetter wasmay be strong enough to produce synchronous firing of supported by the ‘Pain Research Programme’ of theneurons in the ipsilateral SII. Hence, in subjects with a Medical Faculty of the University of Heidelberg.large callosal midbody the peak response in the ipsilateralSII may occur earlier than the peak response in thecontralateral SII. The concept of ipsilateral SII activation

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Source activity in the human secondary somatosensory cortex depends on the size of corpus callosum