Somatosensory and Motor Research, September 2008; 25(3): 149–162

Multiple parietal subdivisions in humans: Tactile activation maps

HAROLD BURTON1,2, ROBERT J. SINCLAIR1, JASON R. WINGERT1, & DONNA L. DIERKER1

1Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO, USA and 2Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA

(Received 1 May 2008; accepted 6 May 2008)

Abstract We focused the present analysis on blood-oxygen-level-dependent responses evoked in four architectonic subdivisions of human posterior parietal operculum (PO) during two groups of tasks involving either vibrotactile stimulation or rubbing different surfaces against the right index finger pad. Activity localized in previously defined parietal opercular subdivisions, OP 1–4, was co-registered to a standard cortical surface-based atlas. Four vibrotactile stimulation tasks involved attention to the parameters of paired vibrations: (1) detect rare target trials when vibration frequencies matched; (2) select the presentation order of the vibration with a higher frequency or (3) longer duration; and (4) divide attention between frequency and duration before selecting stimulus order. Surface stimulation tasks involved various discriminations of different surfaces: (1) smooth surfaces required no discrimination; (2) paired horizontal gratings required determination of the direction of roughness change; (3) paired shapes entailed identifying matched and unmatched shapes; (4) raised letters involved letter recognition. The results showed activity in multiple somatosensory subdivisions bilaterally in human PO that are plausibly homologues of somatosensory areas previously described in animals. All tasks activated OP 1, but in vibrotactile tasks foci were more restricted compared to moving surface tasks. Greater spatial extents of activity especially in OP 1 and 4 when surfaces rubbed the finger pad did not support previously reported somatotopy of the second finger representation in ‘‘S2’’. The varied activity distributions across OP subdivisions may reflect low-level perceptual and/or cognitive processing differences between tasks.

Keywords: Human parietal cortex, magnetic resonance imaging, touch Downloaded By: [Washington University School of Medicine] At: 17:19 21 May 2009 Introduction somatosensory area, VS, and OP 4 to a parietal ventral area, PV (Eickhoff et al. 2006c, 2006d, 2007). Brain imaging studies have confirmed somatosensory Similar somatotopic organizations have been evoked responses in human parietal operculum that noted in S2 and PV subdivisions of monkeys are in addition to those recorded along the post- (Robinson and Burton 1980a; Burton et al. 1995; central . In concordance with studies in nonhu- man primates, the parietal opercular activity was Krubitzer et al. 1995; Qi et al. 2002; Disbrow et al. identified as human ‘‘S2’’ (Burton et al. 1993; 2003; Wu and Kaas 2003; Coq et al. 2004) and OP 1 Ledberg et al. 1995). But the human parietal and OP 4, respectively, of humans (Disbrow et al. opercular cortical subdivision consists of multiple 2000; Eickhoff et al. 2007). Generally, a mirror cytoarchitectonic areas (Disbrow et al. 2000, 2003; reversed somatotopy between S2 and PV in monkeys Eickhoff et al. 2006a, 2006c) that have been also has been noted between OP 1 and OP 4 in considered homologues to subdivisions identified humans (Eickhoff et al. 2007). The reversal occurs at in monkeys: OP 1 to S2, OP 2 to an inferior subdivision borders and reflects representations for parietal vestibular area (PIVC), OP 3 to a ventral distal body anatomy and head with surrounding

Correspondence: Dr H. Burton, Department of Anatomy and Neurobiology, Campus Box 8108, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA. Tel: þ1 314 362 3556. Fax: þ1 314 747 4370. E-mail: [email protected] ISSN 0899–0220 print/ISSN 1369–1651 online ß 2008 Taylor & Francis DOI: 10.1080/08990220802249275 150 H. Burton et al.

representations for more proximal body parts A central question regarding lateral parietal (Eickhoff et al. 2007). In this pattern digits are somatosensory areas is whether they selectively and represented through the middle of the parietal distinguishably respond to different tactile stimula- operculum, across the border between OP 1 and tion paradigms. The current analysis was especially OP 4 (Ruben et al. 2001; Young et al. 2004; Eickhoff aided because all individual fMRI data were et al. 2007), and comparably across the border coincidently registered to OP cytoarchitectonic sub- between S2 and PV in monkeys (Robinson and divisions using a surface-based atlas of the human Burton 1980a; Burton et al. 1995; Krubitzer et al. (Van Essen 2005). Additionally, 1995; Qi et al. 2002; Disbrow et al. 2003; Wu and activity was examined using servo-controlled stimu- Kaas 2003; Coq et al. 2004) and other species lation of the same right index finger pad in two (Krubitzer et al. 1986; Krubitzer and Calford 1992). different protocols. We contrasted results between OP 3 is located at the fundus of the parietal one set of tasks that utilized vibrotactile, punctate operculum and responds to tactile stimulation stimulation and a second set that involved moving (Eickhoff et al. 2006a, 2006c, 2007). VS, the putative surface stimulation. Cognitive complexity also varied monkey homologue of OP 3, has rostral and caudal across the tasks, which allowed contrasts between components that respectively are located medial to tasks with fewer and greater discrimination demands. PV and S2 (Wu and Kaas 2003; Coq et al. 2004). We selectively focused on newly defined human VS-caudal has an anterior to posterior/trigeminal to opercular regions with the goal of determining lumbar-sacral somatotopy along the fundus of the whether each is differentially affected by varied lateral (Qi et al. 2002; Wu and Kaas 2003; cognitive and stimulation factors. Coq et al. 2004) that resembles the topography previously reported for the retroinsular cortex (Ri) in macaques (Robinson and Burton 1980b). However, Materials and methods only a hint of a rostro-caudal somatotopy has been noted in OP 3 (Eickhoff et al. 2007). Unlike The present analysis focused on activity evoked in VS-caudal, OP 3 lies medial to OP 4/PV. A vestibular the parietal operculum by tactile stimulation of an representation in OP 2 occupies the fundal region extended, passively restrained right index finger. medial to OP 1/S2 (Eickhoff et al. 2006d). All image acquisition synchronized to tasks presented Human ‘‘S2’’ responds to manually applied tactile with single event designs (Table I). stimulation even without task relevance (Disbrow For Tasks 1, 2–4, 5–7, and 8 we recorded activity et al. 2000; Ruben et al. 2001; Eickhoff et al. 2006b, in, respectively, 8, 12, 10, and 10 different adults 2007). Cognitively relevant tasks elicit greater (Table I) who gave consent in accordance with activation (Ledberg et al. 1995; Roland et al. 1998; Washington University Human Studies Committee Bodega˚rd et al. 2000, 2001; Nelson et al. 2004; guidelines. Participants self-reported no history of Young et al. 2004; Reed et al. 2005; Burton et al. neurological conditions or head trauma, no current 2008). Sensory linked motor behaviors also evoke medications, and no contraindication to MRI. All responses in ‘‘S2’’ (Binkofski et al. 1999; Inoue et al. but one participant was right-handed based on 2002; Wasaka et al. 2005; Hinkley et al. 2007). responses to a modified Edinburgh handedness Downloaded By: [Washington University School of Medicine] At: 17:19 21 May 2009 Table I. Data sets and image acquisition parameters.

Tasks

1 2–4 5–7 8

Detect freq difference Attend freq/duration Smooth, gratings, shapes Letters

Sample size (N) 8 (8 male) 12 (8 male) 10 (6 male) 10 (7 male) Age, years 45.5 4.5 28.3 3.7 18.5 1.2 43.2 5.2 Right-handed (mean, SE) 85.1, 8.8 92.8, 4.9 94.6, 1.3 70.4, 10.5 Mean accuracy 475% 475%a 495% 485% Scanner 3 T, Allegra 1.5 T, Vision 3 T, Allegra 3 T, Allegra EPI: TR/TE, ms 2840/30 2800/50 2048/25 2500/30 Flip angle 90 90 90 90 Slices/voxel size, mm 32/4 4 4 21/3.75 3.75 6 32/4 4 4 32/4 4 4 Time points per run 167 328 193 154 No. runs per event-type 4 4 2 2 Trials per event-type 68 32 48 38

aPerformance accuracy in prior training sessions. fMRI studies of ‘‘S2’’ 151

inventory (Raczkowski et al. 1974) (Table I, a score Detections were signaled by elevating the left of 100 indicates complete right-handedness). second finger; trials with unmatched frequencies In the tasks utilizing vibrotactile stimulation, were signaled by refraining from any left finger a servo-controlled vibrator (Figure 1A1) applied movement. The test frequencies were 25 or 100 Hz sinusoidal vibrations through a 3.5 mm diameter with displacement amplitudes of 130 and 35 mm, flat plastic probe tip (Burton et al. 2004, 2008). The respectively. The number of 25 and 100 Hz pre- tip contacted the skin through a platform sentations was equal across and within imaging runs. (Figure 1A2) with a 5.5 mm hole, leaving a 1 mm In Task 1 each vibration lasted 750 ms, 300 ms annulus. Vibration amplitudes were suprathreshold gaps separated vibrations in a trial, and 1.5 s intervals and individually adjusted for subjective intensity separated neighboring trials. Three sequential vibra- equalization across applied frequencies. tion trials were followed by a 14 s interval of no A similar temporal structure governed all stimulation. Collectively these were analyzed as vibrotactile stimulation tasks in which individual single 23 s events (Figure 2A). A ‘‘target event’’ trials involved presentation of paired vibrations contained at least one trial where vibration frequen- (Figure 2A, B). Behavioral responses, whether overt cies matched. A ‘‘non-target event’’ involved three with the left hand or covert, were required after each sequential trials of un-matched paired frequencies. trial. Three closely spaced successive trials were For the present analysis we examined activity evoked followed by a longer interval with no stimulation. during the more prevalent ‘‘non-target events’’. Collectively the three trials and following For Tasks 2–4 participants decided whether a no-stimulation interval were analyzed as a single long larger value of a cued parameter occurred first or duration event. second within a trial (Burton et al. 2008). Selective For Task 1 (Figure 2A) participants detected cuing directed participant attention to the parameters whether the paired vibrations in a trial had identical of vibration frequency and duration in Tasks 2 and 3, frequencies. Such trials were rare (7% incidence respectively. The target vibration was stimulation or 17/240 trials across four imaging runs). with a higher frequency for Task 2 and stimulation

A1 B1

A2 B2 Downloaded By: [Washington University School of Medicine] At: 17:19 21 May 2009

Figure 1. Mechanical stimulators. (A1) The vibrator used for vibrotactile stimulation consisted of a titanium shaft that floated on an air-bearing. The latter were housed inside the shown outer titanium tube. A magnetically and electrically shielded electromechanical driver (not shown) was attached to the shaft and was displaced 12 feet from the scanner. (A2) The finger rested against a platform with a central annulus for the probe tip. The platform was attached to the outer tube. (B1) The rotating drum used for surface stimulation consisted of a continuous flexible photopolymer belt that snugly fitted over two fiberglass cylinders. A shielded stepper motor driver (not shown) was attached to the axel of the cylinder located furthest from the scanner. (B2) The finger rested in a small channel whose position could be adjusted to align the finger tip with a selected track along the belt circumference. 152 H. Burton et al.

(A) Detect Rare Matching Vibrations (Task 1) order of the one that changed. On trials with a 1 2112 2 selective cue, vibration frequency and duration stim Non-Target values were manipulated on every trial, but only the resp values of the cued attribute were relevant. Three 1 2212 2 sequential trials were similarly cued, but the tem- stim Target poral order of the targeted parameter values was elevate left finger resp randomly determined for every trial. 0 2.84 8.52 14.2 19.88 In Tasks 2–4 the duration of each vibration varied (see below), 500 ms gaps separated vibrations in a (B) Attend Vibration Parameters (Tasks 2−4) trial, and 3 s intervals separated neighboring trials. Three sequential and similarly cued trials and a stim resp covert 1 or 2 following 13 s no-stimulation interval were collec- cue tively analyzed as a single 28 s event (Figure 2B). Event-types were defined by cue type, which was 0 2.84 8.52 14.2 19.88 25.56 randomized within runs. There were 32 events per (C) Discriminate Surfaces (Tasks 5−7) type that were equally distributed across four imaging runs. stim Attention to the frequency parameter involved two resp button push standards. The low frequency standard was 25 Hz 0 2.5 7.5 12.5 17.5 (SEM: 0 Hz; amplitude mean and SEM: 130 mm 27.5), which was paired with a vibration (D) Identify Letters (Task 8) whose mean was either 14 Hz (1.1 Hz; stim 134 mm 21.3) or 36 Hz (1.3 Hz; 106 mm 20.8); resp voice and a high frequency standard of 180 Hz (11.3 Hz; 30 mm 2.6) was paired with a vibration whose mean 0 2.5 7.5 12.5 17.5 was 136 Hz (12.6 Hz; 38 m 5.2) or 238 Hz TIME (sec) m (14.2 Hz; 29 mm 3.5). Attention to vibration Figure 2. Timelines for tactile stimulation tasks. (A) Task 1 duration involved a single 1000 ms standard. The involved three trials of paired vibration stimulation (stim) in comparison mean shorter interval was 960.4 ms each event. Two vibration frequencies were used (1 ¼ 25 Hz (4.2) and the mean longer interval was 1041 ms and 2 ¼ 100 Hz). Detection of matched paired vibration frequencies required elevation of a left-hand finger (resp). (4.2). The range of vibration amplitudes, frequen- Events containing any trial with matched frequencies were cies, and durations noted above reflected adjust- coded as a Target; events where all three trials contained ments needed to obtain 75% accuracy in every unmatched frequencies were coded as a Non-Target. (B) participant for every task during over-training in Tasks 2–4 involved three trials of paired vibrotactile prior non-imaging sessions. stimulation that were similarly cued (cue). Vibration parameters of frequency and duration varied for each pair. Participants overtly pushed different buttons to Cuing instructed whether attention was to be directed to signal the target order in training sessions when one or both vibration parameters in order to detect the performance data were obtained. During imaging

Downloaded By: [Washington University School of Medicine] At: 17:19 21 May 2009 temporal order of the stimulation at a higher frequency or participants covertly thought 1 or 2 when detecting a longer duration vibration. Covert responses of ‘‘1’’ or ‘‘2’’ target order of first or second of paired stimulation. indicated whether the target parameter was first or second in a pair. (C) Surface stimulation events involved epochs of All participants reported after the scans that the tasks rotary translation of a 40 mm segment of a photopolymer and their perceived target detections were compar- surface across the finger pad. Each imaging run was able to what they experienced during training dedicated to a different surface pattern (Task 5: smooth, sessions. Task 6: horizontal gratings, Task 7: shapes). Identification Trials were visually cued, and cues were con- of specified surface patterns required button pushes (resp) with the left second or third fingers. (D) Surface stimulation tinuously present during stimulation in each event involved rubbing with a string of six identical embossed (Figure 2B). During imaging the cues were words capital letters. Voiced identification of the letter name in printed in white below a white cross and against a Task 8 was recorded and deconstructed with noise unique colored background. When selectively cuing suppression software (Burton et al. 2006). frequency (Task 2) the screen showed ‘‘FREQ’’ against a green background; during selective cuing for duration (Task 3) the screen word was ‘‘TIME’’ presented with a longer duration for Task 3. A non- against a red background; and for neutral cuing informative cue (e.g., neutral cuing) in Task 4 (Task 4) the word was ‘‘BOTH’’ against a screen required that participants divide attention between divided into top half green and bottom half red. The both vibration parameters to identify the stimulus screen was black otherwise except for a white cross. fMRI studies of ‘‘S2’’ 153

In the tasks (5–8) utilizing surface stimulation, a sequential pairs were presented during each trial. servo-controlled rotating drum (Burton et al. 2006) The task involved recognizing whether touched translated a photopolymer printing material across shapes matched. Three 8 mm 8 mm shapes were the finger pad from proximal to distal (Figure 1B1). used (circle, three-sided open square, and a V). The finger rested in a channel that aligned the finger Example combinations were circle–circle vs. circle– pad with a track along the drum belt containing a circle, open square–open square vs. circle–circle, etc. selected pattern (Figure 1B2). Tracks consisted of Whether shapes in the second pair matched those in continuous smooth or interrupted embossed patterns the first varied randomly with equal probability. An (elevated 0.8 mm) arranged in short lengths sepa- event included moving the shapes across the finger rated by smooth segments on a 330 cm flexible belt. and participant button push response to indicate yes Drum speeds were 22 and 30 mm/s, respectively, for or no regarding whether the shapes matched Tasks 5–7 and 8. (Figure 2C). The temporal structure of all surface stimulation Left and right button pushes signaled direction of tasks was similar (Figure 2C, D). Each trial roughness change for Task 6 and match–no-match encompassed a fixed interval of surface movement for Task 7. Buttons had reverse designations for half that included initial rotary acceleration, constant of the participants. The linkage between specified velocity, deceleration, and a variable interval with no button pushes and the two alternative choices was movement when the finger contacted a smooth counterbalanced across the participants. For Tasks surface. Overt behavioral responses occurred after 5–7 a chime heard during drum deceleration signaled movement stopped. Collectively the interval of sur- when to push a button (Figure 2C). face movement, behavioral response, and a variable In Task 8 a string of six identical embossed capital duration of post-movement rest were analyzed as letters rubbed across the skin (Burton et al. 2006). single events. Timing between events was jittered by Target letters were A, I, J, L, O, T, U, and W, which changing the duration of post-movement intervals. are the least confusable when passively translated The distribution of these intervals followed a across a finger (Vega-Bermudez et al. 1991). Letters truncated negative exponential distribution. Total in block capital Arial font were 8 mm high and letter event durations ranged from 12.3 to 22.5 s for Tasks dependent variable widths. Events consisted 5–7 and 15 to 27.5 s for Task 8. Each event was of translating the string with letters presented in a synchronized with image acquisitions. Analyses top-to-bottom direction followed by a pause in (Miezin et al. 2000; Ollinger et al. 2001a, 2001b) rotation during which participants vocally identified considered average event durations of 17.5 and 20 s, the letter (Figure 2D). respectively, for Tasks 5–7 and 8 (Figure 1C, D). In Task 5 a continuous smooth surface rubbed Image processing across the finger; no surface pattern discriminations were required for this task. Participants pushed a We imaged blood-oxygenation-level-dependent response key on every trial upon hearing a chime with (BOLD) contrast responses (Ogawa et al. 1990; either the left second or third fingers on alternative Kwong et al. 1992) using asymmetric spin-echo, runs. echo-planar sequences (EPI) in a 1.5 T Vision In Task 6 embossed 40 mm strips of horizontal scanner for Tasks 2–4 and a 3 T Allegra scanner Downloaded By: [Washington University School of Medicine] At: 17:19 21 May 2009 gratings with variable groove widths and constant (Siemens, Erlangen, Germany) for all other tasks ridge widths of 250 mm rubbed against the skin. (Table I). Whole brain coverage was obtained using These strips consisted of two equal lengths that contiguous, interleaved axial slices, oriented parallel differed in groove widths (gratings with wider groove to the bicommissural plane. Sagittal, T1-weighted widths feel rougher). The task required detecting the magnetization prepared rapid gradient echo direction of roughness change. In all trials a 1000 mm (MP-RAGE) images (1 mm 1mm 1.25 mm) groove width standard was compared to gratings with were used for atlas transformation and cortical groove widths of 1800–2900 mm (i.e., six groove segmentation in each participant. width differences between 800 and 1900 mm). Each Preprocessing all fMRI data corrected for head direction of change and each combination of groove motion within and across runs, adjusted intensity width differences was equally probable (i.e., standard differences due to interleaved slice acquisition, touched first or second). Events encompassed normalized global mean signal intensity across stimulation with one 40 mm grating strip and runs, and compensated for slice-dependent time participant button push responses to signal perceived shifts using sync interpolation. direction of roughness change (Figure 2C). Registration of each structural MRI volume to the In Task 7 four sequential embossed shapes along a 711-2B atlas (Buckner et al. 2004) was through 40 mm length were rubbed against the skin. The computed affine transforms that linked the first same shapes were touched in pairs, and two image volume of each EPI run (averaged over all 154 H. Burton et al.

runs after cross-run realignment) with the PALS-B12 standard mesh using nearest node MP-RAGE images (Ojemann et al. 1997). Images metric mapping. The latter was accomplished after were re-sampled in atlas space to 2 mm3 isotropic participant-specific surfaces were registered to the voxels and spatially smoothed (4 mm FWHM) before PALS-B12 atlas using six standard landmarks and statistical analyses. a spherical registration algorithm applied to the individual and atlas spherical maps (Van Essen Statistical analyses 2005). Contrasts between tasks were based on a common Estimates of the percent MR signal change per voxel metric that reflected the spatial distributions of for the time points of an event relative to baseline activity in different OP regions. The metric involved activity were obtained for each event-type using a nodes selected on each hemisphere’s post-registra- general linear model (GLM). Separate GLMs were tion fiducial surface and especially surface area computed for Tasks 1, 2–4, 5–7, and 8 because each measures that manifested the unique parietal oper- group of tasks involved different event durations cular anatomy in each hemisphere of every indivi- (Figure 2A–D). Each GLM contained regressors for dual. We computed areas for each participant and the time points in specified events, linear drift in MR task and separately for each OP subdivision. The signal across concatenated runs, and a high-pass activity dependent area was computed from nodes filter. whose registered F-test z-scores equaled or exceeded Because the temporal structure of events differed a threshold used for corrected t-test z-score maps.1 (Figure 2A–D), we did not contrast results between An area-proportion-index was computed that was the tasks based on standard response magnitudes, which ratio of the area for the thresholded F-test z-scores in usually are obtained from convolving evoked BOLD an individual and the area of an OP subdivision in responses with a canonical hemodynamic response that person. Thus, statistical analyses relied on a function (Friston et al. 1995). Instead we assessed dependent variable that was an index defined as the activity using an F-test, which evaluated whether ratio of suprathreshold activity dependent area to variance in percent change of MR signal relative to total OP subdivision area. A one-way ANOVA baseline during a particular event-type accounted for assessed task contributions to the distribution of a greater proportion of summed variance than proportions in each OP subdivision. Post hoc t-tests,2 variance from a corresponding interval of baseline with significance levels Bonferroni corrected for activity (noise). Larger F-ratio magnitudes indicate multiple comparisons, contrasted the distribution of BOLD responses evoked during events accounted proportions between selected tasks in different OP for a greater proportion of recorded MR variance. subdivisions. F-ratios were transformed to normalized z-scores (e.g., F-test z-scores). F-test z-scores were evaluated in two ways. First, group whole brain activation analysis was obtained Results for each task using a random effect T-map of the Parietal opercular subdivisions F-test z-scores (Holmes and Friston 1998). Second, the spatial extent of activity thresholded for signifi- Eickhoff and colleagues computed probability maps Downloaded By: [Washington University School of Medicine] At: 17:19 21 May 2009 cance in each OP region by task was assessed. for parietal opercular cytoarchitectonic subdivisions An index computed from these spatial extent (OP 1–4) based on cytoarchitectonic identifications measurements (see below) provided a dependent in ten post-mortem brains (Eickhoff et al. 2006a, variable for task contrasts in random effect ANOVA 2006c). We registered, summed, and mapped linear and post hoc t-tests. Both random effects analyses transformations of these probability maps and were performed after registering the voxelwise F-test subdivision boundaries to a standardized cortical z-scores to the cortical surface of each individual. surface-based atlas (PALS-B12, Van Essen 2005) as described in the Appendix. Most OP regions are hidden within the depths of the Sylvian . Surface mapping However, portions of OP 1 and 4 extend out onto the We generated a fiducial cortical surface per surface of lateral parietal cortex as shown on the hemisphere for each individual using the SureFit average fiducial cortical surface in Figure 3A. algorithm in Caret (Van Essen et al. 2001). Substantial inflation of the cortical surface uncovers The voxelwise F-test z-scores were then registered the parietal operculum and presents a full overview of to surface nodes based on coordinate intersection of all four OP subdivisions (Figure 3B). The OP surface nodes enclosed by that voxel (Burton et al. boundaries drawn in Figure 3B are enlarged and 2008). Next, F-test z-scores at each participant- reproduced in Figure 3C together with overlays of specific cortical surface node were re-sampled to the the T-maps of F-test z-scores for each of the tasks. fMRI studies of ‘‘S2’’ 155

(A) (B)

OP4 OP1 OP1 OP4 OP3 OP2 OP2 OP3

LH RH (C) Task 1 Task 5

4 4 1 1 Detect Freq 2 Smooth 3 2 3 Difference Surface Task 2 Task 6

Discriminate Attend Grating Frequencies Roughness Task 3 Task 7

Attend Identify Durations Shapes Task 4 Task 8

Attend Frequencies and Identify LHLH Durations RHR H LHLH Letters RHR H t-test p value

>0.001 >0.00001

Figure 3. OP ROI mapped to PALS-B12 atlas together with group average random effect t-test maps during different tasks. (A) OP 1 and 4 are partly visible in a lateral view of PALS-B12 average fiducial cortical surface (Van Essen 2005). (B) A full overview of all four OP regions is visible on a very inflated PALS-B12 average cortical surface. Green borders and different colors mark the boundaries of OP subdivisions. (C) T-maps in OP 1–OP 4 for different tasks. Numbers 1–4 in C, respectively, label OP 1–4.

Downloaded By: [Washington University School of Medicine] At: 17:19 21 May 2009 All tactile tasks activated the posterior parietal OP 1. The T-maps show that all tasks activated operculum contralateral to the stimulated right finger approximately the same middle portion of contral- pad. Many tasks also evoked activity in matching ateral OP 1 (Figure 3C). However, Task 1, detecting ipsilateral cortex. The distribution of this activity a difference in vibration frequencies, engaged the across the four OP subdivisions is shown in smallest proportion of OP 1 compared especially to Figure 3C. Task-specific differences in these most other tasks. Progressively greater proportions of T-maps are discussed below. However, consistent OP 1 were affected by Tasks 2–8, respectively. Thus, with the differences shown in Figure 3C, a one-way the area-proportion-index for Task 1 was 30% of ANOVA of the area-proportion-index for each OP OP 1 (Figure 4), for the other vibrotactile stimulation subdivision found significant effects by tasks in all tasks it was 40% (Figure 4) and for all surface contralateral OP subdivisions (Table II(a)). The stimulation tasks (Tasks 5–8) it was 450% ANOVA results from OP subdivisions ipsilateral to (Figure 4). For example, significantly smaller area- stimulation were not significant after correction proportion-indices for Task 2 compared to Task 7 in for multiple ANOVA tests. However, the area- post hoc t-tests illustrate these differences between proportion-index differences in OP 4 were close to spatial extents engaged by vibrotactile and surface significant at 0.05 (Table II(a)). Particular task stimulation tasks (Table II(b)). Similar spatial extent contrasts contributing to these ANOVA results on differences characterized task pairings between other spatial extent differences are considered below. vibrotactile and surface stimulation tasks (Figure 4). 156 H. Burton et al.

Table II(a). One-way ANOVAa. Table II(b). Student’s t-tests.a

Side Subdivision F df p Side Subdivision Task contrast t Df p

LH OP 1 3.35 7, 76 0.0144 LH OP 1 2 vs. 7 2.63 20 0.0081 OP 2 2.97 7, 76 0.0332 OP 2 1 vs. 8 4.38 16 0.0010 OP 3 3.4 7, 76 0.0132 OP 3 3 vs. 8 6.69 16 50.0001 OP 4 3.35 7, 76 0.0144 OP 4 1 vs. 4 1.59 18 0.048 RH OP 1 2.5 7, 76 0.0916 OP 4 4 vs. 8 2.86 20 0.0080 OP 2 1.32 7, 76 1.0000 OP 4 5 vs. 8 1.6 18 0.0640 OP 3 1.38 7, 76 0.9100 RH OP 1 2 vs. 7 0.37 22 0.3587 OP 4 2.73 7, 76 0.0556 OP 2 1 vs. 8 3.79 16 0.0015 OP 3 3 vs. 8 1.91 20 0.0354 a Shaded cells significant after multiple comparison correction. OP 4 1 vs. 4 2.14 18 0.0230 OP 4 4 vs. 8 1.64 20 0.0588 OP 4 5 vs. 8 3.93 18 0.0005

a The T-maps show generally less extensive task Shaded cells significant after multiple comparison correction. effects in ipsilateral (right) OP 1. The map was virtually blank for Task 1, sparse for the other vibrotactile stimulation tasks, largely confined to a Task 7) did not differ, possibly due to greater and single medial/inferior focus for surface stimulation unequal variance amongst these task area-propor- Tasks 5–7, and most extensive for Task 8 tion-indices. (Figure 3C). Consistent with the T-maps, the area- proportion-index for Task 1 was 20% of OP 1, near 30% for the remaining vibrotactile tasks, 50% for OP 3. The T-maps indicated that contralateral OP surface stimulation tasks (Tasks 5–7), and 460% for 3 was affected by nearly every task, especially in its Task 8 (Figure 4). Despite these differences, there most inferior and anterior aspects (Figure 3C). The was no significant difference across tasks in the area-proportion-indices were 30% for all vibrotac- ANOVA for ipsilateral OP 1 (Table II(a)) and, not tile tasks, 440% for the two surface discrimination unexpectedly, for example, between the smaller Tasks 6 and 7, and 70% for the letter recognition area-proportion-index for the vibrotactile Task 2 Task 8 (Figure 4). These differences probably compared to the surface stimulation Task 7 in post explain the significant ANOVA (Table II(a)). hoc t-tests (Table II(b)) or any other comparable In post hoc t-tests, the area-proportion-index was pairings. Although these results suggest the absence significantly greater for Task 8 compared to each of task differences in ipsilateral OP 1, they also may of the vibrotactile tasks. Comparable differences indicate greater variability and possibly a smaller characterized other pairings between the other effect size in ipsilateral OP 1. These negative results vibrotactile vs. surface stimulation Tasks 6 and 7. in ipsilateral OP 1 are not explained by differences in The T-maps in ipsilateral OP 3 showed a variety handedness because all but one participant reported of activation patterns from the different tasks. The right hand dominance. between task variances also differed significantly, which possibly was responsible for no significant Downloaded By: [Washington University School of Medicine] At: 17:19 21 May 2009 results in the ANOVA for this OP region OP 2. The T-maps show slight involvement of (Table II(a)). The area-proportion-index was great- contralateral OP 2 for Tasks 1–7 and indicate more est for Task 8 (Figure 4) and this was significantly substantial spatial extent for Task 8 (Figure 3C). greater than the 510% index for Task 1 Similarly, the area-proportion-indices were all525% (Table II(b)). for Tasks 1–7 but 450% for Task 8 (Figure 4). Consistent with these relative relationships, for example, area-proportion-index for Task 8 was OP 4. The T-maps indicated that all tasks impacted significantly greater than that for Task 1 OP 4 bilaterally (Figure 3C). The ANOVA (Table II(b)). (Table II(a)) indicated significantly different area- The T-maps generally revealed more of an impact proportion-indices across the tasks. In contralateral on ipsilateral OP 2 (Figure 3C). A consequence was OP 4 differences possibly responsible for these that most area-proportion-indices exceeded 25% ANOVA results involved area proportions of 515% except for Task 1. However, only the area- for Task 1, 30% for the remaining vibrotactile tasks proportion-index during the letter identification and surface stimulation with a smooth surface, 40% (Task 8) was significantly greater than during the for the two surface discrimination Tasks 6 and 7, and vibrotactile detection Task 1 (Table II(b)). Other 70% for the letter recognition Task 8 (Figure 4). task contrasts (e.g., Task 2 vs. Task 8 or Task 2 vs. Post hoc t-tests confirmed these distinctions; fMRI studies of ‘‘S2’’ 157

LH RH

0.8 OP10.8 OP1

0.6 0.6

0.4 0.4

0.2 0.2

0.0 0.0 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8

0.8 OP2 0.8 OP2 0.6 0.6

0.4 0.4

0.2 0.2

0.0 0.0 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8

0.8 OP3 0.8 OP3 0.6 0.6

0.4 0.4

0.2 0.2

0.0 0.0 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 Proportion of OP Subdivision Area with Suprathreshold z-scores 0.8 OP40.8 OP4 0.6 0.6

0.4 0.4

0.2 0.2

0.0 0.0 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 Tasks

Figure 4. Area-proportion-indices by OP subdivision and task. Bars show means and SEM. Downloaded By: [Washington University School of Medicine] At: 17:19 21 May 2009

the area-proportion-index was significantly greater Thus, the area-proportion-index for Task 1 differed for Task 8 compared to each of the vibrotactile tasks significantly from that for Task 4, and similar (Table II(b)). Comparable differences characterized differences were noted for Task 5 vs. Task 8 pairings between the other vibrotactile vs. surface (Table II(b)). stimulation Tasks 6 and 7. Additionally within the vibrotactile tasks and with a more lenient, Discussion uncorrected p-value, the area-proportion-index for the least demanding frequency detection Task 1 was The current findings in humans confirm results from significantly lower than that for Task 4 (Table II(b)). animal studies of multiple lateral parietal somato- Similarly, in ipsilateral OP 4, area-proportion-indices sensory subdivisions (Burton et al. 1995; Krubitzer ranged from 15% in Task 1 to 70% for Task 8 et al. 1995; Qi et al. 2002; Disbrow et al. 2003; (Figure 4). Post hoc t-tests indicated that within Wu and Kaas 2003; Coq et al. 2004). Additionally, both sets of tasks significantly smaller area- the distinguishable activation patterns for OP 1, 3, proportion-indices were present in the tasks that and 4 subdivisions strengthen the suggestion that involved possibly less discrimination complexity. homologues to, respectively, S2, VS, and PV in 158 H. Burton et al.

monkeys exist in humans (Eickhoff et al. 2006c, tasks and for the surface stimulation tasks the cluster 2007). The varied extent and location of activity in is mostly separate from the affected zone in OP 1. these OP subdivisions also draw attention to The foci in ipsilateral OP 4 similarly were located previously reported somatotopy in these subdivisions close, but not always adjoined to the cluster in OP 1 given tactile stimulation of the same right second for several tasks (e.g., 3 and 5–8). Thus, the T-maps finger pad in all tasks. A principal finding was that for most tasks only poorly instantiate a representation the spatial extents of activity in OP subdivisions of adjoining digit representations at the border differed by task. These response distributions poten- between OP 1 and 4. The T-maps for Task 8 tially arose from differences in low-level perceptual diverged bilaterally from a predicted central digit processes associated with vibrotactile compared to zone due to widespread involvement of, especially, surface stimulation. Additionally, however, the contralateral OP 4. cognitive demands varied across the tasks even Some divergence from predicted somatotopy was within the sets that involved comparable stimulation found for most tasks, and especially for the surface protocols. Consequently, we also consider whether stimulation tasks. Principally, the T-maps for these potential cognitive differences contributed to the tasks were more extensive than previously described observed differences in area-proportion-indices. hand/finger representations (Disbrow et al. 2000; Eickhoff et al. 2007). One explanation for this difference is that a greater area of the finger pad Somatotopy in OP subdivisions was stimulated with the moving surfaces. However, Consensus on somatotopy in lateral parietal cortex of maps varied for different surface stimulation tasks monkeys is that the digits/hand map to the middle of despite comparable contact with the finger pad. For PV and S2 with a mirror-symmetric pattern for body example, the map from stimulating with embossed representations across the border between these letters showed no focal representation and left little regions (Burton et al. 1995; Krubitzer et al. 1995; of OP 1 for the rest of the body representation. Qi et al. 2002; Disbrow et al. 2003; Wu and Kaas Possibly greater cognitive demands associated with 2003; Coq et al. 2004). In humans, Eickhoff and tactile letter recognition engaged more than a colleagues noted distal body representations segregated representation of digit 2 in OP 1. adjoined at the extremities at the border between However, even the maps noted with vibrotactile OP 4 and OP 1 (Eickhoff et al. 2007). The identified stimulation in the present study might have reflected representation across the border is probably coex- cognitive behavior in contrast to mapping using tensive with a finger-two region previously ascribed passive tactile stimulation protocols. Thus, OP map to ‘‘S2’’ (Disbrow et al. 2000; Ruben et al. 2001). characteristics are malleable and probably influenced In general, these findings were partially confirmed. by task demands even in the most topologically Thus, as expected the T-maps for vibrotactile and defined OP 1 and 4 regions. most surface stimulation tasks (e.g., Tasks 2–7) Prior neurophysiological studies in behaving maca- showed affects through the middle of contralateral ques also reported discrepancies in the receptive OP 1. Nevertheless, these results are not entirely field structure of individual neurons within the somatotopic. The map for Task 8 showed extensive component digit/hand representation in S2. Thus, involvement across nearly all of OP 1. Additionally, intermixed within expected somatotopic areas for the Downloaded By: [Washington University School of Medicine] At: 17:19 21 May 2009 the maps in ipsilateral and contralateral OP 1 digits were neurons with widespread multi-digit, differed. The focal site in ipsilateral OP 1 was hand, arm, etc. receptive fields (Robinson and located further anterior and inferior for Tasks 3 Burton 1980a; Sinclair and Burton 1993; Fitzgerald and 5–7. Again, the T-maps for Task 8 contained no et al. 2006b). Large receptive fields for some ‘‘hand’’ particular focus, but involved most of ipsilateral OP S2 neurons were observed when monkeys actively 1. Differences between contralateral and ipsilateral touched and cognitively processed distributed maps have not been described previously. However, surfaces (Sinclair and Burton 1993). Such findings the observed differences plausibly suggest that support the suggestion that cognitive tasks and/or bilateral processing of tactile inputs from unilateral differences in perceptual processing can influence stimulation might involve different components of at observed somatotopy in parietal opercular subdivi- least OP 1. sions OP 1 and 4. A predicted central location for the digits was only Maps in OP 3 occupied the superior limiting partly confirmed in OP 4. Thus, in contralateral OP sulcus anterior to OP 1 in a site that possibly 4, the principal foci were centrally located and coincides with a hand representation described for contiguous with the group T-maps in OP 1, either VS-rostral or caudal in monkeys (Robinson especially for most vibrotactile tasks and possibly and Burton 1980b; Qi et al. 2002; Coq et al. 2004). the surface stimulation Tasks 6 and 7. However, Somatotopy in VS-caudal is head to trunk from there is a separate cluster as well for the vibrotactile anterior to posterior; a reversed posterior to anterior/ fMRI studies of ‘‘S2’’ 159

head to trunk somatotopy is likely in VS-rostral low-level stimulus features. Accordingly, tasks (Qi et al. 2002; Wu and Kaas 2003; Coq et al. 2004). utilizing surface stimulation provide greater A precise topography in OP 3 could not be mechanical translation across the finger pad than determined from current data. Furthermore, OP 3 tasks employing punctate vibrotactile stimulation lies medial to OP 4 (PV), which contrasts with and might therefore provoke more extensive activity locating VS-caudal medial to S2 in monkeys distributions. Such low-level stimulation factors (Robinson and Burton 1980a; Burton et al. 1995; possibly contributed to the several instances of Krubitzer et al. 1995; Qi et al. 2002; Disbrow et al. significantly smaller area-proportion-indices for the 2003; Wu and Kaas 2003; Coq et al. 2004). A hand vibrotactile compared to the surface stimulation area in OP 3 was previously based upon observing tasks. Two findings suggest that additional factors activation when stimulating the hand in one might be involved. individual, but a ‘‘hand’’ area was not shown in a First, it was not universal that the area- group summary ‘‘maximum likelihood representa- proportion-indices for any vibrotactile task were tion’’ (Eickhoff et al. 2007). The current findings always smaller than those for any surface stimulation confirm activation of OP 3 from stimulating the tip task. Thus, significant differences mostly involved of digit 2 and support identifying it as yet another contrasts between the least cognitively demanding lateral parietal somatosensory subdivision. However, frequency detection vibrotactile, and most surface whether OP 3 is a homologue for VS-caudal or stimulation tasks; there were no significant differ- VS-rostral is indefinite. Possibly additional somato- ences between the area-proportion-indices for the topic mapping will establish further correspondence more demanding selective and divided vibrotactile to the anterior–posterior organizations previously attention and the surface stimulation tasks that described in monkeys for the two components of VS. involved discriminating grating roughness or shape T-map results in OP 2 were especially prominent differences. Secondarily, significant differences pri- for most surface stimulation tasks, but were also marily involved contrasts between the cognitively obtained for several of the vibrotactile tasks. These more demanding letter recognition surface stimula- findings suggest that OP 2 is more than a vestibular tion vs. each vibrotactile task. Additionally, signifi- area as previously reported (Eickhoff et al. 2006d). cant differences were detected between some tasks Eickhoff and colleagues discounted a somatosensory that used the same mode of stimulation and hence role for OP 2 because they found that tactile identical low-level perceptual features. Examples activation of OP 2 had the lowest mean probability with vibrotactile stimulation involved significantly compared to other parietal opercular subdivisions smaller area-proportion-indices for Tasks 1 vs. 4 (Eickhoff et al. 2007). The OP 2 activity was also within OP 4 bilaterally. Task 1 involved simple noted where it adjoined anticipated responses in detection of rarely encountered trials where vibration nearby OP 3 during tactile stimulation of the legs frequencies matched. In contrast, Task 4 required (Eickhoff et al. 2007), which again suggested possible more cognitive resources because both parameters of problems with activity registrations within the vibration frequency and duration were attended and deepest/fundal parts of the parietal operculum. The processed in a divided tactile attention paradigm. OP 2 clusters noted here, especially those associated Similarly, for tasks with surface stimulation smaller with the vibrotactile stimulation tasks, were separated area-proportion-indices occurred for Tasks 5 or 6 vs. Downloaded By: [Washington University School of Medicine] At: 17:19 21 May 2009 from other more superficial foci, which discounts 8 in ipsilateral OP 4 and for Task 5 vs. 8 in the possibility that the observed clusters were contralateral OP 3. All surface stimulation tasks a consequence of spillover from registration mis- again involved the same low-level perceptual fea- alignments of activity. An interpretation of the tures; and these tasks required processing multiple current findings is to suggest a possible homology surface features that had to be remembered, pro- for OP 2 with a caudal somatosensory area identified cessed, and integrated for accurate discriminations. in animals that is located inferior and posterior to S2 However, recognizing embossed letters possibly (e.g., Ri or VS-caudal) (Robinson and Burton 1980a; entailed perceiving and remembering more shape Burton et al. 1995; Krubitzer et al. 1995; Qi et al. features plus sublexical recollection. 2002; Disbrow et al. 2003; Wu and Kaas 2003; These differences suggest that varied cognitive Coq et al. 2004). If this notion is correct, then OP 3 demands influenced the spatial extent of activity in might be appropriately considered the homologue some OP regions. A smaller area-proportion-index of VS-rostral. occurred for the task that was cognitively less demanding (e.g., Task 1). Prior human imaging studies also noted that cognitively relevant tasks Possible factors affecting activity in OP subdivisions elicited greater activation of ‘‘S2’’ (Ledberg et al. One contributing factor to the varied maps 1995; Roland et al. 1998; Bodega˚rd et al. 2000, associated with the different tasks was differences in 2001; Nelson et al. 2004; Young et al. 2004; 160 H. Burton et al.

Reed et al. 2005; Burton et al. 2008). Fitzgerald et al. Burton H, Fabri M, Alloway K. 1995. Cortical areas within the (2004, 2006a) similarly suggested that parietal connected to cutaneous representations in areas 3b and 1: A revised interpretation of the second somatosensory opercular neurons in macaques, which respond best area in macaque monkeys. J Comp Neurol 355:539–562. to active touch, possibly contribute to higher cogni- Burton H, McLaren DG, Sinclair RJ. 2006. Reading embossed tion, especially when coding tactile and propriocep- capital letters: An fMRI study in blind and sighted individuals. tive sensations derived from touching the complex Hum Brain Mapp 27:325–339. features of objects. The underlying intriguing Burton H, Sinclair RJ, McLaren DG. 2004. Cortical activity to vibrotactile stimulation: An fMRI study in blind and sighted hypothesis is that activity in lateral parietal somato- individuals. Hum Brain Mapp 23:210–228. sensory subdivisions concerns higher cognitive Burton H, Sinclair RJ, McLaren DG. 2008. Cortical network processes rather than simply providing an additional for vibrotactile attention: A fMRI study. Hum Brain Mapp somatotopic map of stimulated body parts. 2:207–221. Burton H, Videen TO, Raichle ME. 1993. Tactile-vibration- activated foci in insular and parietal-opercular cortex studied with positron emission tomography: Mapping the second somatosensory area in humans. Somatosens Mot Res Acknowledgments 10:297–308. Coq JO, Qi H, Collins CE, Kaas JH. 2004. Anatomical and We gratefully acknowledge D. G. McLaren and functional organization of somatosensory areas of the lateral S. Dixit for assistance with data collection and fissure of the New World titi monkey (Callicebus moloch). analyses and J. Kreitler and Dr G. Perry for the J Comp Neurol 476:363–387. design and construction of the tactile stimulators. Disbrow E, Litinas E, Recanzone GH, Padberg J, Krubitzer L. 2003. Cortical connections of the second somatosensory area Supported by NIH grants NS31005 and NS37237. and the parietal ventral area in macaque monkeys. J Comp Declaration of interest: The authors report no Neurol 462:382–399. Disbrow E, Roberts T, Krubitzer L. 2000. Somatotopic conflicts of interest. The authors alone are organization of cortical fields in the lateral sulcus of responsible for the content and writing of the paper. Homo sapiens: Evidence for SII and PV. J Comp Neurol 418:1–21. Eickhoff SB, Amunts K, Mohlberg H, Zilles K. 2006a. The human parietal operculum. II. Stereotaxic maps and Notes correlation with functional imaging results. Cereb Cortex 16:268–279. 1. We computed average z-score maps from the F-test z-scores Eickhoff SB, Grefkes C, Zilles K, Fink GR. 2007. The that were registered to the PALS-B12 surface nodes. The average F-test z-scores per node were assessed with somatotopic organization of cytoarchitectonic areas on the t-tests (Bosch 2000) that were corrected for multiple tests human parietal operculum. Cereb Cortex 17:1800–1811. (Bonferroni for 69 328 t-tests based on the number of nodes Eickhoff SB, Lotze M, Wietek B, Amunts K, Enck P, Zilles K. in the PALS-B12 cortical surface exclusive of the midline) 2006b. Segregation of visceral and somatosensory afferents: An and degrees of freedom (N 1 varied with sample size (N) fMRI and cytoarchitectonic mapping study. Neuroimage per task) at a p-value threshold of 0.01. These corrected 31:1004–1014. t-values were transformed into z-score maps scaled to the Eickhoff SB, Schleicher A, Zilles K, Amunts K. 2006c. The same p-value threshold. human parietal operculum. I. Cytoarchitectonic mapping of 2. Error was the subject by task interaction term. subdivisions. Cereb Cortex 16:254–267. Eickhoff SB, Weiss PH, Amunts K, Fink GR, Zilles K. 2006d. 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each OP ROI were formed as follows: (1) sequentially imposed on the smoothed data, assured that after subtracting from each OP subdivision the remaining averaging across adjacent nodes, the retained node three OP ROI probability maps (e.g., OP 1OP 2, represented data from at least one post-mortem OP 1OP 3, and OP 1OP 4), (2) converting retained brain. Selected nodes were assigned a unique color positive values from each subtraction to binary by self- value, and CARET software created borders division, (3) creating exclusive OP domains by multi- around these painted areas (Van Essen 2005). plying the binary coded maps resulting from each Manual border smoothing (1–2 nodes) eliminated set of subtractions per OP ROI, and (4) revising the points jutting out of and into adjacent subdivisions probability maps by multiplying the exclusive binary and imposed continuous, juxtaposed boundaries OP domain with the original, un-subtracted smoothed between ROI. Figure 3A shows surface-based probability map for each OP ROI. registration of OP ROI painted areas and To draw contiguous boundaries around a borders tucked into the parietal operculum on the surface-based registration of an OP ROI, all nodes PALS-B12 average fiducial surface; Figure 3B shows associated with the subdivision were selected surface-based registration of ROIs on a very inflated using a minimum probability of 10%. This criterion, surface. Downloaded By: [Washington University School of Medicine] At: 17:19 21 May 2009