A fronto-parietal circuit for tactile object discrimination:

NeuroImage 19 (2003) 1103–1114

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A fronto-parietal circuit for tactile object discrimination: an event-related fMRI study M. Cornelia Stoeckel,a,* Bruno Weder,b Ferdinand Binkofski,a,c Giovanni Buccino,d N. Jon Shah,e and Ru¨diger J. Seitza a

Department of Neurology, University Hospital Du¨sseldorf, Du¨sseldorf, Germany b Department of Neurology, Kantonsspital St. Gallen, St. Gallen, Switzerland c Department of Neurology, University Hospital Lu¨beck, Lu¨beck, Germany d Institute of Human Physiology, University of Parma, Parma, Italy e Institute of Medicine, Research Centre Ju¨lich, Ju¨lich, Germany Received 23 August 2002; revised 1 March 2003; accepted 18 March 2003

Abstract Previous studies of somatosensory object discrimination have been focused on the primary and secondary sensorimotor cortices. However, we expected the prefrontal cortex to also become involved in sequential tactile discrimination on the basis of its role in working memory and stimulus discrimination as established in other domains. To investigate the contributions of the different cerebral structures to tactile discrimination of sequentially presented objects, we obtained event-related functional magnetic resonance images from seven healthy volunteers. Our results show that right hand object exploration involved left sensorimotor cortices, bilateral premotor, parietal and temporal cortex, putamen, thalamus, and cerebellum. Tactile exploration of parallelepipeds for subsequent object discrimination activated further areas in the dorsal and ventral portions of the premotor cortex, as well as parietal, midtemporal, and occipital areas of both cerebral hemispheres. Discriminating a parallelepiped from the preceding one involved a bilateral prefrontal–anterior cingulate–superior temporal– posterior parietal circuit. While the prefrontal cortex was active with right hemisphere dominance during discrimination, there was left hemispheric prefrontal activation during the delay period between object presentations. Delay related activity was further seen in the anterior intraparietal area and the fusiform gyrus. The results reveal a prominent role of the human prefrontal cortex for somatosensory object discrimination in correspondence with recent models on stimulus discrimination and working memory. © 2003 Elsevier Science (USA). All rights reserved. Keywords: Somatosensory; Tactile; Working memory; Prefrontal cortex; Event-related functional MRI

Introduction The discrimination of objects with respect to their geometric characteristics by active touch is more than a simple combination of touch and kinesthesia (Re´ve´sz, 1950). Indeed, the tactile exploration of object features is mediated by dedicated finger movements, which have been described in detail by Roland and Mortensen (1987). Recent neuroimaging studies have shown that different cytoarchitectonic * Corresponding author. Moorenstr. 5, 40225 Du¨sseldorf, Germany. Fax: ⫹49-211-8118485. E-mail address: [email protected] (M.C. Stoeckel).

subareas of the somatosensory cortex specifically code roughness, edge, and shape characteristics of objects (Bodegård et al., 2001). The superior parietal lobule and the secondary somatosensory cortex in conjunction with the ventral premotor cortex have been shown to build the basic circuit for tactile object identification (Binkofski et al., 1999). Conversely, well-defined, circumscribed brain lesions of the parietal cortex are known to disturb object exploration and recognition associated with tactile apraxia (Binkofski et al., 2001a). Further, patients with lesions in the dorsal portion of the supramarginal gyrus and secondary somatosensory cortex may be impaired in identifying objects by tactile

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exploration in spite of preserved object manipulation and basic somatosensory capacities. This phenomenon has been termed tactile agnosia (Caselli et al., 1991, 1993; Reed et al., 1996). Last but not least, lesions affecting the anterior portion of the intraparietal sulcus disturb the precision grip for picking up an object for tactile exploration (Binkofski et al., 1998). While these data speak to the importance of parietal cortical areas for information processing in the somatosensory modality, we assumed that further areas are necessary for sequential tactile discrimination of objects related to short-term information storage, retrieval, comparison, and decision making. Possibly, these putative areas remained hidden in previous neuroimaging experiments due to the integration of data over time (e.g., Bodegård et al., 2000a, 2000b; O’Sullivan et al., 1994; Roland and Larsen, 1976; Roland et al., 1998; Seitz et al., 1991). We particularly expected the prefrontal cortex to be involved in tactile object discrimination. Recent neuroimaging studies show the involvement of the human lateral prefrontal cortex in functions such as mnemonic storage, the manipulation of memory content, and problem solving (Duncan and Owen, 2000; Owen et al., 1999; Petrides, 1995). The processes that have gained most interest up to now are related to the concept of “working memory,” introduced by Baddeley in 1986. In the context of sequential discrimination tasks, the role of working memory is to keep sampled information online for subsequent comparison and decision making. This function is thought to be sustained by prefrontal areas in interaction with posterior sensory and association areas (Courtney et al., 1997; Paulesu et al., 1993; Postle et al., 1999, 2000; Smith et al., 1998). Using neuronal recordings in monkeys a contribution to somatosensory discrimination from both somatosensory (Herna´ndez et al., 2000; Zhou and Fuster, 1996) and inferior prefrontal neurons (Romo et al., 1999) was reported. The cooling of the dorsolateral prefrontal cortex in monkeys produced reversible deficits in a sequential somatosensory discrimination task (Shindy et al., 1994). To disentangle the brain areas related to tactile discrimination of shape in humans we employed functional magnetic resonance imaging (fMRI). This method has been shown to be able to separate sequentially activated cerebral areas with event-related experimental designs (e.g., Henson et al., 2000). The purpose of this fMRI study was two-fold. First, we aimed to identify the cerebral areas related to feature extraction by active touch. Second, we hypothesized prefrontal involvement in sequential tactile discrimination of objects based on recent experimental data and theoretical models. We were interested to examine how our data would contribute to the recent debate on working memory and the functional subdivisions within the prefrontal cortex. Preliminary data have been presented in abstract form elsewhere (Stoeckel et al., 2001).

Methods Subjects Seven male subjects (aged 22– 44 years) participated in the study. Handedness was assessed with the Edinburgh Handedness Inventory (Oldfield, 1971) in the modified version by Salmaso and Longoni (1985). An average index of 89% indicated strong right-handedness in our subjects. None of the subjects suffered from any known neurological or psychiatric disease at the time of the experiment. Prior to scanning subjects gave written informed consent in accordance with the Declaration of Human Rights in Helsinki 1975. The study was approved by the Ethics Committee of the Heinrich-Heine-University Du¨sseldorf. Behavioural task The discrimination of sensory information can be conceptualized experimentally as a sequential two-alternative forced-choice task (e.g., Roland and Mortensen, 1987; Seitz et al., 1991). Basically a pair of stimuli is presented and after presentation of the second stimulus a decision is required whether the stimuli are different or equal concerning a specific feature. The paradigm has the advantage to demand a sustained level of directed attention. In this study subjects either sequentially explored parallelepipeds (Ps) or spheres (Ss) with their right hand. All objects were made from nonmagnetic hard aluminium and had identical mass (11.5 cm3, 32.5 g). While Ss were different neither in shape nor size, four kinds of Ps differing in their perceivable oblongness were used (i.e., there were differences both in the major axes and the square bases). Differences of the long axis were above or below the discrimination threshold known from previous studies by Roland and Mortensen (1987) and Weder et al., (1998). Subjects lay supine inside the scanner with their heads immobilized and their eyes closed. The experimenter was triggered auditorily via headphones by a PC from outside the scanner to present and remove the objects. Each object was presented for 5 s, while the interval between object presentations varied between 12 and 17 s (Fig. 1). This ensured jittered onsets of all conditions in relation to the onsets of volume acquisition necessary for equal sensitivity in all acquired slices. Subjects continuously explored the presented objects with the fingers of their right hand. While Ss (identical physical characteristics) simply had to be manipulated, subjects were instructed to discriminate the sequentially presented Ps (differing in oblongness) pairwise. When exploring the second parallelepiped of a pair (P2), subjects were asked to extend their right thumb only when they thought P2 was more oblong than the object presented before (P1). Object pairs were pseudo-randomized in such a way that thumb extensions were expected for half of the pairs. Subjects were free to choose an exploration strategy but

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Fig. 1. Structure and time frame of the sequential two-alternative forced choice paradigm. Ss, spheres; PI, first parallelepiped; P2, second parallelepiped.

were asked to keep fingers moving for the whole 5-s period of object presentation. The stimulation procedure was videotaped through a window from outside the scanner room using a close-up lens for offline analysis of the behavioural data. Exploration of Ss and discrimination of Ps was carried out in four separate runs (two each) in pseudorandomized order across subjects. Presentation of Ss and Ps was kept separately to ensure a maximum number of discriminations per run. Further, from a practical point of view, this made the presentation of objects less vulnerable to errors by the experimenter, as already the fast presentation of the different Ps in the exact pseudorandomized order was quite demanding. During each run 68 objects were presented so that 34 decisions were due in case of object discrimination. Subjects did not leave the scanner between runs. Image acquisition Scanning was performed on a Siemens Vision 1.5-T scanner (Siemens, Erlangen, Germany) using an EPI-GE scanning sequence with TR ⫽ 5 s, TE ⫽ 66 ms, flip angle ⫽ 90°. Volumes consisted of 30 transaxial slices covering the whole brain and were oriented according the AC-PC line with an in-plane resolution of 3 ⫻ 3 mm, 4-mm slice thickness, and an interslice gap of 0.4 mm. In each run 255 volumes were acquired. The first 3 volumes of each session were discarded and did not enter the analysis. An anatomical T1-weighted image with high resolution consisting of 128 sagittal slices and 0.9 ⫻ 0.9 mm in-plane resolution was also acquired in each subject (TR ⫽ 40 ms, TR ⫽ 5 ms, flip angle ⫽ 40°).

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⫻ 10 ⫻ 10-mm Gaussian filter. During normalization, images were resampled to a voxel size of 2 ⫻ 2 ⫻ 2 mm. The structural T1-weighted image was coregistered to the mean image of the functional images. Realignment parameters as determined in the realignment step were used as confounding covariates. Data were filtered in time using a Gaussian low-pass filter of 4 s and a high-pass filter of 70 s. All data were scaled to the grand mean. Data were analyzed in a fixed-effects model and using the hemodynamic response function provided by SPM. Presentation of P1 and P2 were modelled separately. An additional regressor described the delay period within object pairs (when information was expected to be stored for the following comparison). The duration of all conditions was modelled explicitly (5 s for objects, 12–17 s for the delay period). The interval between object pairs (with no requirement of information storage) served as an implicit baseline. Possible smearing effects due to temporal smoothness of the fMRI data were expected to be equivalent in the delay period and the implicit baseline and, thus, cancelled out for this condition. The exploration of Ss was modelled within the same design matrix. Since no differences were detected between the “first” and “second” sphere in a separate analysis, all spheres were pooled for further analysis to increase the statistical power. No delay period was modelled for these runs. To identify the cerebral areas involved in object exploration a conjunction of activations in Ss and Ps was calculated. All activation areas beyond a voxel level threshold of P ⬍ 0.01, corrected for multiple comparisons and within clusters of ⱖ 20 voxels, are reported. However, as single subject activations can dominate the results of a fixed effects analysis, we further used the individual contrasts for conjunction analyses across subjects (Friston et al., 1999). In this study conjunctions with z ⬎ 3.5 served as an indicator for consistent activation across subjects. All activation seen in the fixed effects analysis is reported in the results section, while areas also seen in the conjunction analyses are specially indicated in the tables. Only those areas will be discussed that showed up in both analyses. All reported coordinates are transformed from MNI-space (used by SPM and named after the Montreal Neurology Institute) to the Talairach-space using a matlab script provided at http://www.mrc-cbu.cam.ac.uk/Imaging/mnispace. To exclude activations due to susceptibility artefacts we overlaid all contrasts on the mean of all functional images. No activation was found to be affected by susceptibility artefacts.

Results Data processing Behavioural data Data were analyzed using the statistical parametric mapping software SPM99 (Wellcome Department of Cognitive Neurology, London, UK; http://www.fil.ion.ucl.ac.uk/spm). Images were realigned, normalized, and spatially smoothed with a 10

The discrimination rate for the rectangular parallelepipeds was in the range predicted from previous observations (Roland and Mortensen, 1987; Seitz et al., 1991; Weder et

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Table 1 Activation areas during exploration of objects (Ss and Ps)a Functional regions

Anatomical localization

x

y

z

Z value

MI Lb Dorsal premotor cortex Lb Dorsal premotor cortex Rb Ventral premotor cortex Lb Ventral premotor cortex Rb Ventral prefrontal cortex Lb CMAb Posterior cingulate gyrus Lb SI Lb SI Rb SII Lb SII Rb Midtemporal cortex L Midtemporal cortex R Putamen Lb Putamen Rb Thalamus Lb Thalamus Rb Cerebellum Rb Cerebellum Lb Cerebellum Rb Cerebellum Lb Cerebellum Rb

Precentral gyrus Middle frontal gyrus Precentral gyrus Precentral gyrus Precentral gyrus Inferior prefrontal gyrus Cingulate gyrus Cingulate gyrus Postcentral gyrus Postcentral gyrus Retroinsular cortex Postcentral gyrus Middle temporal gyrus Middle temporal gyrus Putamen Putamen VP1 thalamus VP1 thalamus Anterior cerebellum Anterior cerebellum Inferior posterior cerebellum Inferior posterior cerebellum Cerebellar vermis

⫺44 ⫺24 40 ⫺44 63 ⫺34 0 ⫺8 ⫺40 57 ⫺55 61 ⫺53 57 ⫺24 28 ⫺14 14 22 ⫺24 16 ⫺18 4

⫺17 ⫺7 ⫺7 ⫺4 8 18 0 ⫺17 ⫺26 ⫺19 ⫺19 ⫺17 ⫺54 ⫺58 ⫺2 ⫺2 ⫺17 ⫺15 ⫺54 ⫺53 ⫺70 ⫺68 ⫺66

43 61 54 2 14 1 42 41 53 43 16 17 6 5 ⫺2 ⫺2 5 6 ⫺11 ⫺18 ⫺39 ⫺39 ⫺8

⬎8 ⬎8 ⬎8 ⬎8 ⬎8 6.34 ⬎8 ⬎8 ⬎8 ⬎8 ⬎8 ⬎8 ⬎8 ⬎8 ⬎8 ⬎8 ⬎8 ⬎8 ⬎8 ⬎8 ⬎8 ⬎8 ⬎8

a MI, primary motor cortex; CMA, cingulate motor area; SI, primary somatosensory cortex; SII, secondary somatosensory cortex; VPl, ventral posterior thalamus, lateral portion; R, right; L, left. The columns x, y, z refer to Talairach coordinates in millimeters (mm). b This table is based on a conjunction analysis of spheres and parallelepipeds. Areas also activated in the conjunction analysis of these contrasts across subjects are indicated by b(P ⬍ 0.05, corrected for multiple comparisons).

al., 1998). That is, 77% (range, 62– 84%) of object pairs were correctly discriminated. The videotape revealed continuous finger movements in all subjects during all tasks. Types of manipulations could be classified as encompassings (very few), rolls (spheres only), and dynamic digital (Roland and Mortensen, 1987). Imaging data The exploration of the objects evoked a blood flow increase in the left primary motor, bilateral dorsal and ventral premotor, and the primary and secondary somatosensory cortex (Table 1). There was also activation in the frontomesial cortex that mapped to the cingulate motor area (CMA) extending dorsally into the adjacent ventral portion of the supplementary motor area (SMA) and into the left posterior cingulate cortex. Additional bilateral activation was seen in the posterior part of the middle temporal gyrus. Subcortically, there was bilateral activation of the putamen, the thalamus, and both cerebellar hemispheres including the cerebellar vermis (Table 1). By contrasting P1 with Ss we obtained the cortical areas that were more active during the tactile exploration of rectangular parallelepipeds by active touch for the purpose of subsequent tactile discrimination than during the simple exploration of spheres. This yielded frontal activation in bilateral ventral premotor and prefrontal areas, and right

dorsal premotor cortex. There was also posterior activation, which was located to the primary somatosensory cortex, the supramarginal gyrus, and the caudal portion of the intraparietal sulcus of the left hemisphere (Fig. 2). Right hemispheric parietal activation was seen in posterior portion of the intraparietal sulcus and the inferior parietal lobule. Parietal activation clusters also included the anterior intraparietal sulcus (AIP) bilaterally. Further activation was seen in the posterior portion of the middle temporal gyrus and the occipital cortex (Table 2). To obtain those areas probably involved in the discrimination process we contrasted the activation pattern during P2 with that during P1. In both conditions the objects had to be explored for extraction and encoding of object features. However, discrimination was required during the exploration of the second parallelepiped only. This contrast showed bilateral prefrontal, anterior cingulate, left superior temporal, and bilateral posterior parietal activation (Table 3). The prefrontal cortical activations were more pronounced in the right hemisphere and were located in the right ventral premotor and prefrontal cortex, left dorsal premotor, bilateral opercular, and right anterior prefrontal cortex (Fig. 3). To exclude any effect for this contrast due to the discriminative thumb movements following the presentation of P2 we conducted a further analysis. This analysis compared P2 followed by a positive response (movement of the thumb) with P2 followed by a negative response (no move-

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Fig. 2. Activation related to object exploration (P1 vs. Ss) superimposed on the group’s mean T1-weighted magnetic resonance image. Sections at Talairach z levels ⫽ 2, 12, and 46 mm (left to right) show activation in the left ventral premotor and prefrontal cortex, the right ventral and dorsal premotor cortex, bilaterally along the intraparietal sulcus, the left midtemporal cortex, and the occipital cortex. Right in the images corresponds to right in the subjects. P1, first parallelepiped; Ss, spheres.

ment of the thumb). For this comparison we did not find any significant voxel at P ⬍ 0.05 corrected for multiple comparisons. Note that only 34 motor responses were carried out on average during the 40-min period of object exploration using the same (right) hand that was also manipulating the objects. Furthermore, there were no differences in primary sensorimotor areas when contrasting P2 to P1. Finally, we were interested in the activation during the delay period between the presentation of P1 and P2. We found frontal activation, which was located in the ventral premotor and prefrontal, dorsal and anterior prefrontal cortex, and the anterior midfrontal cortex of the left hemisphere (Fig. 4). Further activation was seen in the anterior portion of the left intraparietal sulcus and, bilaterally, the fusiform gyrus (Table 4). Discussion When objects are compared sequentially as in this study, extracted features have to be stored in working memory for

subsequent comparison during the interval between object presentations. In such a design discrimination only takes place during exploration of the second object. Event-related fMRI provides the opportunity to separate the processes related to object discrimination from those related to object exploration by using separate regressors for the presentation of the first and the second object of a pair. By modelling the delay period between object presentations, activity related to short-term information storage can also be shown as will be discussed in detail below. Object exploration The exploration of both the spheres and the parallelepipeds activated a sensorimotor circuit including primary sensorimotor cortex, dorsal and ventral premotor cortex, CMA and the secondary somatosensory area, and subcortically the putamen, thalamus, and the cerebellum. This is in agreement with earlier studies (Boecker et al., 1995; Seitz et al., 1991; Ginsberg et al., 1988; Roland and Larsen, 1976).

Table 2 Activation areas related to tactile exploration of the first parallelepiped (P1) of a pair as compared with spheres (Ss)a Functional regions b

Dorsal premotor cortex R Ventral premotor cortex Lc Ventral premotor cortex Rb Ventral prefrontal cortex L Ventral prefrontal cortex Rc SI Lc Supramarginal gyrus Lb (including AIPc) Supramarginal gyrus Rb (including AIPc) pIPS Rb cIPS Lc Midtemporal cortex Lb Midtemporal cortex R Visual cortexb a

Anatomical localization

x

y

z

Z value

Precentral gyrus Precentral gyrus Precentral gyrus Inferior frontal gyrus Inferior frontal gyrus Postcentral gyrus Supramarginal gyrus Supramarginal gyrus Intraparietal sulcus Intraparietal sulcus Middle temporal gyrus Middle temporal gyrus Lingual gyrus

30 ⫺53 57 ⫺42 50 ⫺61 ⫺46 50 38 ⫺20 ⫺48 50 ⫺6

⫺1 11 11 43 33 ⫺16 ⫺29 ⫺27 ⫺42 ⫺66 ⫺62 ⫺60 ⫺71

55 22 25 0 9 32 38 42 52 49 1 ⫺2 11

7.06 ⬎8 ⬎8 6.10 5.99 ⬎8 ⬎8 ⬎8 ⬎8 ⬎8 ⬎8 7.06 7.75

SI, primary somatosensory cortex; pIPS, posterior intraparietal sulcus; cIPS, caudal intraparietal sulcus; R, right; L, left. The columns x, y, z refer to Talairach coordinates in millimeters (mm). b Areas also activated in the conjunction analysis are indicated by b(P ⬍ 0.05, corrected for multiple comparisons) or c (z ⬎ 3.5).

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Table 3 Activation areas during tactile exploration being more activated by the second parallelepiped (P2) than by the first parallelepiped (P1) of a paira Functional regions

Anatomical localization

x

y

z

Z value

Dorsal premotor cortex Lb Ventral premotor cortex Rb Ventral prefrontal cortex Rb Opercular prefrontal cortex Rb Opercular prefrontal cortex Lb Anterior prefrontal cortex Rb ACC Rb (including pre-SMAc and CMAc) STP Lb Posterior parietal cortex Rb Posterior parietal cortex Lb

Precentral gyrus Inferior frontal gyrus Inferior frontal gyrus Inferior frontal gyrus Inferior frontal gyrus Middle frontal gyrus Cingulate gyrus Superior temporal gyrus Inferior parietal lobule Inferior parietal lobule

⫺42 40 53 38 ⫺34 48 6 ⫺42 42 ⫺61

0 7 22 21 25 48 31 ⫺23 ⫺56 ⫺45

44 25 21 ⫺11 ⫺11 ⫺16 32 10 39 28

7.37 7.73 7.35 ⬎8 ⬎8 ⬎8 ⬎8 6.58 7.36 5.77

a ACC, anterior cingulate cortex; SMA, supplementary motor area; CMA, cingulate motor area; STP, superior temporal polysensory area; R, right; L, left. The columns x, y, z refer to Talairach coordinates in millimeters (mm). b,c Areas also activated in the conjunction analysis are indicated by b(P ⬍ 0.05, corrected for multiple comparisons) or c(z ⬎ 3.5).

Since the geometric characteristics of spheres are identical for all surface points and the spheres were all of the same size, an implicit extraction of features by subjects was redundant and, therefore, unlikely during sphere exploration. We, therefore, assume that the conjunction of sphere and parallelepiped exploration showed only those cerebral areas involved in controlling fractionated finger movements. For the discrimination task subjects actively explored

rectangular parallelepipeds. Unlike in spheres, the relevant geometric information for parallelepipeds was not contained in the curvature but lay in the length of the edges. Different proportions of the same types of fractionated finger movements have been described for the discrimination of spheres and parallelepipeds (Roland and Mortensen, 1987). Above that, finger movements during exploration of the parallelepipeds were purposeful and goal directed. Therefore, we subtracted the activation during Ss from that during P1,

Fig. 3. Activation related to object discrimination (P2 vs. P1) superimposed on the group’s mean T1-weighted magnetic resonance image. Sections at Talairach z levels ⫽ ⫺12, 8, 22, 38, and 50 mm (left to right, top to bottom) display activation in right opercular, ventral and anterior prefrontal cortex, right ventral premotor cortex, left opercular prefrontal cortex, the cingulate cortex, left SII, and the right posterior parietal cortex. Right in the image corresponds to right in the subjects. P2, Second parallelepiped; P1, first parallelepiped; SII, secondary somatosensory cortex.

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Fig. 4. Activation related to the delay period between P1 and P2 superimposed on the group’s mean T1-weighted magnetic resonance image. Sections at Talairach z levels ⫽ ⫺18, ⫺2, 12, 28, and 42 mm show activation in left dorsolateral prefrontal, anterior prefrontal, ventral prefrontal and ventral premotor cortex, the left anterior intraparietal sulcus, and, bilaterally, the fusiform gyrus. Right in the image corresponds to right in the subjects. P1 and P2, first and second parallelepipeds.

aiming to identify the cerebral areas additionally involved in object exploration by active touch. As summarized in Table 2, the resulting activation pattern included bilateral ventral premotor and prefrontal cortex and parietal areas as similarly reported by Binkofski et al. (1999) for tactile object identification. The concerted activation of the ventral premotor cortex together with activation of the AIP point to the higher degree of goaldirected finger movements required for object exploration compared to pure object manipulation (Binkofski et al.,

1999). Supramarginal activation as seen in this study has been reported previously in length discrimination tasks (Bodega˚rd et al., 2001; O’Sullivan et al., 1994) and has been discussed as a candidate for shape representation (Bodegard et al., 2001). Focal lesions in the inferior parietal lobule are known to produce a selective deficit in shape perception and representation with preserved lower somatosensory functions, spatial abilities, and tactile exploration behaviour (Reed et al., 1996). Admittedly, different objects as used in this study may also require different exploration strategies

Table 4 Activation areas during the delay period between the first (P1) and second parallelepiped (P2)a Functional regions

Anatomical localization

x

y

z

Z value

Ventral premotor L Ventral prefrontal L Dorsolateral prefrontal Lb Anterior prefrontal cortex Lb Midfrontal cortex L AIP Lb Fusiform gyrus Lb

Inferior frontal gyrus Inferior frontal gyrus Middle frontal gyrus Middle frontal gyrus Middle frontal gyrus Intraparietal sulcus Fusiform gyrus

Fusiform gyrus Rb

Fusiform gyrus

⫺49 ⫺44 ⫺40 ⫺34 ⫺36 ⫺38 ⫺42 ⫺14 ⫺26 30

14 36 40 42 56 ⫺39 ⫺45 ⫺49 ⫺80 ⫺66

12 11 26 ⫺21 3 41 ⫺1 ⫺3 1 3

5.99 6.69 5.97 6.62 6.14 7.18 5.94 5.75 5.19 5.91

b

a b

AIP, anterior intraparietal sulcus; R, right; L, left. The columns x, y, z refer to Talairach coordinates in millimeters (mm). Areas also activated in the conjunction analysis are indicated by b(z ⬎ 3.5).

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including different levels of grip force and provide the brain with different information, which in turn may affect the cerebral activation patterns (Bodegård et al., 2001; KuhtzBuschbeck et al., 2001). Further activation of posterior areas included the caudal portion of the left intraparietal sulcus, the left posterior middle temporal gyrus, and the visual cortex. While the caudal portion of the intraparietal sulcus (cIPS) has recently been associated with control of action (Ehrsson et al., 2001; Seitz and Binkofski, 2003) and attention to action (Culham and Kanwisher, 2001), the posterior temporal lobe has been described as part of the ventral stream for object identification (e.g., Ungerleider and Haxby, 1994). Together with the concomitant activation of the visual cortex, this points to visual imagery as one possible strategy for geometric feature encoding (Kosslyn et al., 1999; Le Bihan et al., 1993). Encoding of information as required for object discrimination is known to activate the prefrontal cortex (Cabeza and Nyberg, 2000). Correspondingly, we found bilateral activation located in the ventral portion of the prefrontal cortex. To summarize, the exploration of objects by active touch activates a set of areas, some of them probably related to the executive control of goal directed finger movements and the coding of somatosensory object configuration (ventral premotor cortex, AIP, and supramarginal gyrus), while others have to do with directed attention, higher order object representation, and enconding (cIPS, occipital cortex, middle temporal gyrus, and ventral prefrontal cortex). Object discrimination To identify the cerebral areas important for tactile object discrimination, we contrasted the activation pattern during P2 with that during P1. As a number of processes were probably involved in object discrimination compared to exploration, such as comparison, working memory processes, decision making, response selection, and response preparation, a number of areas were expected to be seen for this contrast. Our design did not permit to separate these processes directly. However, we will argue that the activations seen for this contrast were due to the concerted action of higher cognitive processes excluding low level motor or touch related activations, which were similar both in quality and quantity in P1 and P2. In agreement with our expectations, we found bilateral premotor and prefrontal activation together with activation of the posterior parietal cortex and left superior temporal gyrus (Table 3, Fig. 3). Premotor and parietal areas are engaged in processing of sensorimotor information (Binkofski et al., 1999; Bodegård et al., 2001; Seitz et al., 1991). The superior temporal gyrus has recently been described as a polymodal integration area (Karnath, 2001). Neurons in the putative homologue area STP (superior temporal polysensory area) in monkeys are known to respond to visual, sensory, and auditory input (Desimone and Gross, 1979; Bruce et al., 1981). Although the STP has mainly been

investigated within the visual domain, Milner and Goodale (1995) point out its possible role in more abstract object representation. However, the contribution of the superior temporal gyrus for object discrimination in humans is the object of further research. The additional activation of the pre-SMA may be related to movement selection (Deiber et al., 1991) for the appropriate response. We will discuss the prefrontal activation in a separate section (see below). Delay related activation When task relevant information had to be stored for subsequent comparison left lateralized frontal activation was seen together with activation of AIP and bilateral activation of the fusiform gyrus in this experiment (Table 4). Notably, this delay related activation was weaker in the conjunction analysis than for the other conditions. This probably reflected differing individual strategies, which were not completely defined by task or instruction (Seitz et al., 2000). Across different modalities frontal and posterior association cortices have been reported in the context of short-term information storage (Smith and Jonides, 1997; Courtney et al., 1997; Postle et al., 1999, 2000). Evidence in the somatosensory domain is limited apart from studies in monkeys, which showed delay related activation in the somatosensory cortex (Zhou and Fuster, 1996) and the prefrontal cortex (Romo et al., 1999) using single cell recordings. In this study we were able to show activation of the anterior intraparietal sulcus. This structure has been related to the execution and the imagery of self-generated movements (Binkofski et al., 2000; Gerardin et al., 2000). In monkeys this area is projecting to the ventral premotor cortex (Rizzolatti et al., 1998). The concerted activation of both areas during the delay period suggests that coding of precisely tuned actions related to object exploration is stored for subsequent comparison. This is assisted by the fusiform gyrus, which has been shown to serve as a supramodal area with a prominent role in object matching (Binkofski et al., 2001b). Prefrontal activation in short-term information retention and stimulus discrimination During object exploration and discrimination, as well as during the delay period between objects, there was prominent activation of a number of subfields in the prefrontal cortex. Previous human neuroimaging studies have demonstrated that the maintenance of verbal (e.g., Cohen et al., 1997), visual (e.g., Courtney et al., 1997), and visuospatial (Smith et al., 1996; Rowe et al., 2000) information during working memory tasks engages the prefrontal cortex. Delay related activation in the inferior convexity of the prefrontal cortex was also shown for somatosensory discrimination by single cell recordings in monkeys (Romo et al., 1999). The functional subdivision of the lateral prefrontal cortex has been an issue of much debate recently. Some authors argue for a modality-specific subdivi-

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sion of the prefrontal cortex (Goldman-Rakic, 1987; Levy and Goldman-Rakic, 1999). Others suggest material-unspecific areas that are dedicated to supramodal higher cognitive processes (Petrides, 1994, 1995, 2000; Nystrom et al., 2000; Owen, 1997, 2000). Petrides (1994, 1996) relates the mid-ventrolateral prefrontal cortex to the active retrieval of information from the posterior cortical association areas. Strong connections between the posterior parietal cortex and the prefrontal cortex allow for information transfer from specific unimodal processing areas to the prefrontal cortex when information has to be kept on-line (Petrides and Pandya, 1984; Selemon and Goldman-Rakic, 1988). A recent review by Fletcher and Henson (2001) more generally states the involvement of the ventrolateral prefrontal area to processes such as updating and maintenance of information. In contrast, processes such as information manipulation activate the dorsolateral prefrontal cortex (Duncan and Owen, 2000; Fletcher and Henson, 2001). Applying these concepts to our data, we would like to argue as follows. Ventral prefrontal activation during object exploration can be related to “information updating” and the retention of stimulus related information using the terminology of Fletcher and Henson (2001). Note that ventral prefrontal activation is not seen in object identification (e.g., Binkofski et al., 1999). While studies using verbal material have consistently shown left hemispheric activation during updating or “information encoding” (e.g., Demb et al., 1995; Kopleman et al., 1998; Wagner et al., 1998a), right hemispheric activation as in this study was shown before for the encoding of nonverbal material (Kelley et al., 1998; Wagner et al., 1998b). The right ventral prefrontal activation during exploration or information updating/encoding was clearly different from the left ventral prefrontal activation during the retention interval. As during the exploration of P1 there is right ventral prefrontal activation during the presentation of P2. Since encoding of object features is thought to be the same during the exploration of P1 and P2, the more dorsal and posterior activation focus during P2 compared to P1 suggests the involvement of processes beyond enconding during P2. This underlines the existence of separate processes within the ventral prefrontal cortex during exploration, retention, and discrimination, respectively. As suggested by Fletcher and Henson (2001) further process-specific subdivisions are likely to exist beyond the coarse division of the prefrontal cortex in its ventral, dorsal, and anterior portion. In addition to left ventral prefrontal activation the dorsal and anterior prefrontal cortex was also activated during the delay period. Although memory load was not high with only one object to be compared, the maintenance of somatosensory information might require a higher degree of monitoring (dorsal prefrontal cortex) and control (anterior prefrontal cortex according to Fletcher and Henson, 2001). Rowe et al. (2000) emphasize the involvement of the dorsolateral prefrontal cortex in response selection rather than in working memory. While maintenance of information and response selection have often been confounded, in our exper-

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iment they were clearly separated in time. Thus, our results point in a different direction with dorsolateral activation during the delay and no dorsolateral activation during the discrimination period when a response had to be selected. In addition to dorsolateral activation Rowe et al. (2000) report ventral prefrontal activation related to response selection, which is very close to our right opercular prefrontal focus during object discrimination, when response selection should indeed take place. Activation of the anterior cingulate cortex (ACC), probably including the pre-SMA and CMA as seen in our study, has also been implicated in response selection (Picard and Strick, 1996) and in selecting actions in general (Posner and Raichle, 1994). This area has been activated during the delay period in other studies and has been related to motor preparation to select a response immediately after the presentation of the test stimulus. As mentioned above, there is a clear difference between our experiment and most other studies on working memory: while usually the response follows the presentation of the test stimulus immediately, the presentation of the probe lasted 5 s in our study. Thus, there was no need and no option for anticipatory motor preparation during the delay period between object presentations. Consistent with the interpretation of Picard and Strick (1996), we see rather extensive ACC activation during P2 compared to P1. Alternative interpretations of the role of ACC include motivational (e.g., Mesulam, 1990) and attentional processes (Posner and Raichle, 1994). While the motivational differences between the exploration of P1 and P2 should be negligible, the attentional demands during the exploration of P2, including information encoding, retrieval, and decision making, are probably greater than during the exploration of P1. Likewise, attentional demands should differ between P1 and Ss. However, when contrasting these two conditions, we do not see any differences in ACC activation. Therefore, the exclusive association of just one cognitively defined process with an activation and vice versa might be inadequate for higher order cognitive areas (e.g., LaBar et al., 1999). Finally, activation within the anterior prefrontal cortex is suggested to reflect a higher level of executive control, namely maintaining intentions, goals, and products of a task while performing another (Fletcher and Henson, 2001). We observed right anterior prefrontal activation during the presentation of P2, which might be related to the organization of the processes required in parallel, i.e., exploration, discrimination, and decision making. The main areas discussed here in the context of attention, response selection, and higher executive control, i.e., the opercular and anterior prefrontal cortex and ACC, have also been described with closely corresponding coordinates as being specific to retrieval from memory as opposed to encoding (Nyberg et al., 2001). This is surprising inasmuch as retrieval demands are supposed to be minimal in this study, as the critical information has to be held online in working memory up to the presentation of the probe, while

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encoding and retrieval were carried out in two different runs in the study by Nyberg et al. (2001). However, in their study further processes beyond retrieval versus encoding distinguished one condition from the including response selection during information retrieval. In general, our data are compatible with the idea of process-specific subdivision of the human prefrontal cortex. This interpretation does not exclude additional materialspecific subdivisions within hemispheres, possibly within larger process-specific areas (Goldman-Rakic, 1987; Levy and Goldman-Rakic, 1999; Fletcher and Henson, 2001). Interestingly, the lateralization of prefrontal activation changes throughout the different stages of a trial in this experiment. We report different patterns of prefrontal activation for the encoding, maintenance, and discrimination of tactile information. However, we are not able to uniquely attribute the different activation foci to different processes within conditions. Further studies are needed to investigate the precise role of the different prefrontal and parietal areas involved. For example, studies that manipulate the degree of memory load required are indicated, as are studies that combine different stimulus modalities. Also, our results might not generalize to all kinds of tactile object discrimination and might vary depending on many factors, such as the hand used for object exploration. As for this study, it has also become clear that different interpretations for the multiple activation foci in the context of working memory, attention, and response selection are possible. They might not even exclude each other, as our recording techniques and models of cognitive task components are probably still too coarse (LaBar et al., 1999). Conclusion To the best of our knowledge this is the first neuroimaging study of humans to investigate the role of the prefrontal cortex in working memory and stimulus discrimination within the tactile domain. Our study demonstrates left lateralized prefrontal and parietal activation for short-term storage of somatosensory information and right lateralized prefrontal activation during tactile object discrimination. Our results extend recent models on the prefrontal cortex and its contribution to higher cognitive information processing as established in the verbal, visual, and visuospatial domain by demonstrating their relevance and applicability for the somatosensory domain.

Acknowledgments This study was supported by the German Research Council (SFB 194) and a stipend by the CNR (Comitato Nazionale della Ricerca) to G.B.

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