1 EA 1880-IFR 19, Hôpital Neurologique, Bâtiment B13, and , 2 Hôpital Neurologique, Service de Neurochirurgie A, 59 Bd Pinel, 69003 Lyon, France , Hôpital Neurologique, Service d'Exploration Fonctionnelle Neurologique et d'Epileptologie, 59 Bd Pinel, 69003 Lyon, France
François Mauguière, Hôpital neuro-logique Pierre Wertheimer, Service de Neurologie Fonctionnelle et d'Epileptologie, 59 Boulevard Pinel, 69394 Lyon cedex 03, France. Email: mauguier{at}univ-lyon1.fr.
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Abstract |
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Introduction |
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In this study, we report both painful and non-painful somaes-thetic sensations elicited by cortical stimulation of the insular cortex in patients undergoing a depth stereotactic recording (stereo-electroencephalography, SEEG) in the course of the pre-surgical evaluation of their temporal lobe epilepsies. Our data show that the posterior part of the insular cortex is involved in the processing of both painful and innocuous somaesthetic inputs. Furthermore, their respective topographical distribu-tions overlap within this cortical area.
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Materials and Methods |
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The 43 patients included in this study (29 women and 14 men) were investigated at the Neurological Hospital in Lyon between January 1996 and November 2000. Language lateralization was assessed by intracarotid amobarbital test in all patients. Among the 36 right-handed patients, 35 had a left language representation and one a bilateral language representation. Among the seven left-handed patients, four had a left language representation, two had a bilateral language representation and one had a right language representation. All patients suffered from a drug-resistant temporal lobe epilepsy (TLE) and underwent a SEEG in the course of their presurgical investigation. Cortical structures to be explored were chosen according to video-EEG recordings of seizures, interictal [18F]fluoro-deoxyglucose positron emission tomography (18-FDG PET), interictal and ictal single photon emission tomography (SPECT) and cerebral magnetic resonance imaging (MRI) data. The decision of insular implantation in the patients of this study was based on the existence of ictal symptoms (such as lip and face paraesthesiae, auditory or gustatory hallucinations, laryngeal contraction, hypersaliva-tion, simple motor signs and post-ictal paresis) suggesting an early spread of the discharge to perisylvian structures (Isnard et al., 2000). Twenty-four patients presented a right TLE and 19 a left TLE.
Stereotactic Implantation and Insular Site Location
The stereotactic implantation technique used is that described by Talairach and Bancaud (Talairach and Bancaud, 1973). A cerebral angiography is first performed in stereotactic conditions using an X-ray source 4.85 m away from the patient's head, eliminating the linear enlargement due to X-ray divergence. In order to reach the pertinent cortical target, the stereotactic coordinates (Talairach and Tournoux, 1988
) of each electrode [x for the medio-lateral axis, with x = 0 being the coordinate of the sagittal interhemispheric plane; y for the rostro-caudal axis, y = 0 being the coordinate of the frontal plane passing through the vertical anterior commissure (VAC); z for the vertical axis, z = 0 being the coordinate of the horizontal plane passing through the anterior and posterior commissures (ACPC plane)] are calculated preoperatively on the individual cerebral MRI previously enlarged at scale 1. Cerebral MRI and angiographic images are easily superimposed to avoid any risk of vascular injuries during implantation.
At the end of the surgery, a post-implantation frontal X-ray was taken and superimposed on MRI images to verify the final position of each implanted electrode with respect to targeted anatomical structures.
Electrodes are implanted perpendicular to the mid-sagittal plane and can be left in place chronically up to 15 days. The electrodes have a diameter of 0.8 mm and 515 recording contacts, depending on their length. Contacts are 2 mm long and are separated by 1.5 mm from one another. The insular cortex was investigated using trans-opercular electrodes. In all cases, only the first and second deepest contacts of the trans-opercular electrode were found to be strictly located in the thickness of the insular cortex as checked on superimposed MRI and X-ray images (Fig. 1A). A total of 93 insular sites were explored, 49 in the right and 44 in the left insular cortex. Each of these insular sites was localized using the stereotactic coordinates of the deepest contact of the corresponding trans-opercular electrodes. The x coordinate (depth of implantation) was verified on the post-implantation frontal X-ray whereas the strict perpendicular trajectory of the electrode, verified on both the frontal and sagittal post-implantation X-rays, ensured that the preoperatively calculated y and z coordinates had been preserved. The estimated spatial error of this insular site location technique is ±2 mm in the three dimensions due to several factors: MRI slice thickness of 1 mm, MRI definition (pixel size) of 0.9 mm; pooling of sites of all patients on a single MRI saggital slice of the insular cortex, whether this slice was extracted from a standardized atlas (Montreal National Institute standard brain) or from the individual MRI of one of our patients (see below).
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A current regulated neurostimulator designed for a safe diagnostic stimulation of the human brain was used (Babb et al., 1980). Square pulses of constant polarity were applied between the two deepest contacts of the trans-opercular electrodes located in the insular cortex (see Fig. 1A
). Two modes of stimulation were used; low frequency stimulation (LFS): 1 Hz, 13 ms, 15 mA applied during 510 s and high frequency stimulation (HFS): 50 Hz, 0.10.5 ms, 0.86 mA applied during 5 s. These parameters were chosen to avoid any tissue injury [charge density per square pulse <55 µC/cm2; see Gordon et al. (Gordon et al., 1990
)]. These parameters, along with the bipolar mode of stimulation using adjacent contacts, ensured a good spatial specificity with respect to the desired structure to be stimulated (Nathan et al., 1993
). HFS was used in all patients and at least once on each insular site. LFS was only performed in the first 20 patients and then abandoned due to its poor efficiency in terms of evoked clinical responses. Stimulation of cortical areas is a routinely applied procedure used in our unit during SEEG recordings to map functionally eloquent cortex and epileptogenic areas. Patients were fully informed of the aim of this investigation and gave their consent before entering this phase of the presurgical evaluation of their epilepsy. During stimulation, patients were sitting in bed and were asked to relax.
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Results |
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Because only one to three insular sites were stimulated per patient, individual data remained poorly informative. Thus, the topographic and somatotopic analysis of our responses were performed by pooling sites where responses were obtained on a single sagittal insular image. In Figure 1 all stimulated sites, whether right or left, are plotted on a sagittal section of the insular cortex of the MNI (Montreal National Institute, Canada) standard brain (Fig. 1B
) and on the corresponding slice of one of our patients (Fig. 1C
). Due to inter-individual variations, the borders and anatomical details of the MNI brain slice are blurred as compared with those of the individual MRI slice. However, as can be seen in Figure 1
, the sampling of the insular cortex was very similar using either of these two types of brain section. This plotting shows that most of the insular surface has been explored except the most anterior part of the insular cortex (y > to 15 mm). For illustration's sake, we plotted sites of stimulation on the individual sagittal MRI slice in other figures.
Painful Sensations Evoked by Insular Cortex Stimulation
Painful sensations were elicited in 17 insular sites (17/93; 18.2%) in 14 patients (14/43; 32.5%). Mean intensity of stimulation was 2.2 mA ± 0.9. Twelve sites were located in the right and five in the left insular cortex. Pain was elicited only during HFS, without AD on 13 sites (11 patients) and with a localized AD in two sites (in two patients). The two sites, both located in the left insular cortex of one patient where the painful sensations were followed by a diffusing AD, are excluded from the follow-ing discussion.
The 15 sites where pain was elicited in the absence of AD or with a localized AD were located in the upper posterior part of the insular cortex (Figs 2A and 4A). Pain intensity could vary from mild to intolerable but was not related to the presence or absence of a localized AD, nor to stimulation intensity. The occurrence of an intolerable painful sensation led us to im-mediately stop the stimulation, which then only lasted for about 1 s instead of 5 s. Pain disappeared as soon as the stimulation was interrupted except in a few cases where the intense pain was followed by a sore feeling that could last up to 1 min after the end of the stimulation. Painful sensations were located contra-lateral to the stimulation site or bilaterally when midline parts of the body were involved. Whereas limb sensations were elicited across the posterior part of the insular cortex, face, ear and nose painful sensations (the cephalic representation) were mostly elicited in a limited area in the upper anterior part of the posterior section of the insular cortex (Fig. 2B
). Qualities of the evoked pain were described as a burning, a stinging or a disabling sensations. Electrical shocks or discharges were also reported (Fig. 2C
). Since all elicited sensations comprised a part of the contralateral body and since the anatomical location of the right and left reactive sites within the insular cortex did not differ significantly (MannWhitney test; two-tailed P > 0.66), coordinates of insular sites of both hemispheres were pooled to calculate mean coordinates of the insular pain representation. These mean coordinates were x = 31.2 ± 4.9 mm, y = 16.4 ± 6.3 mm, z = 13.2 ± 7.6 mm (Table 1
).
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Non-painful Somaesthetic Sensations Evoked by Insular Cortex Stimulation
Non-painful somaesthetic sensations were elicited in 21 insular sites (21/93; 22.5%) in 16 patients (16/43; 37.2%). Nine sites were located in the left and 12 in the right insular cortex. Three of these 16 patients also reported painful evoked sensations described in the preceding section. Painful and non-painful somaesthetic sensations were evoked on different sites except for one site where a first LFS induced a non-painful cold somaes-thetic sensation in the contralateral arm and a second HFS stimulation induced an extremely painful electric shock in the contralateral half of the body. All non-painful somaesthetic-evoked responses but one were obtained using HFS. Sensations were elicited in the absence of AD in 18 sites (13 patients) and with a localized AD in three sites (in three patients). No diffusing AD was observed during non-painful somaesthetic sensations. Mean intensity of stimulation was 2.4 ± 1.8 mA.
Most reactive sites were located in the posterior part of the insular cortex (Figs 3A and 4A). These non-painful sensations were felt contralateral to the stimulation or bilaterally when midline parts of the body were concerned. They involved the face, the ear and/or the throat when stimulated sites were located in the upper part of the posterior section of the insular cortex and the limbs when sites were distributed in its inferior part (Fig. 3B
). They were reported as warmth, cold or tingling sensations. Tingling and warmth sensations were evoked throughout the posterior part of the insular cortex. The only cold sensation was obtained by stimulating the upper posterior part of the insula (Fig. 3C
). Since all sensations comprised at least a part of the contralateral body and since anatomical locations of right versus left reactive sites within the insular cortex did not differ significantly (MannWhitney test; two-tailed P > 0.23), coordinates of insular sites of both hemispheres were pooled to calculate mean coordinates of the non-painful insular somaes-thetic representation. These mean coordinates were x = 32 ± 3.5 mm, y = 13.1 ± 10.6 mm, z = 7.8 ± 8.3 mm (see Table 2
), values that did not differ significantly from those of the insular pain representation (Student's t-test; two-tailed P > 0.05; Fig. 4B
).
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Discussion |
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Insular stimulations in our study were performed in epileptic patients. One could therefore argue that the responses we obtained are related to an abnormal (epileptogenic) cortex, or a cortex that has been submitted to repetitive fits leading to plastic changes (Gloor, 1990; Fish et al., 1993
). Nonetheless, and concerning the painful responses, these were not reported in previous studies which were also performed in epileptic patients.
The proximity of the second somatosensory area (SII) with respect to the insula also raises the question as to the specificity of our responses. Even considering the current density spatial distribution during bipolar stimulation (Nathan et al., 1993), the threshold value leading to an effective stimulation of SII would have to be known in order to evaluate a possible involvement of SII by stimulations of the neighbouring insular cortex. The main argument favouring the specificity of our insular stimulations is that painful responses could never be obtained when stimu-lating directly SII using identical stimulation parameters (personal observations). This is coherent with the fact that Penfield and Jasper also never reported such painful responses when stimulating SII (Penfield and Jasper, 1954
). Furthermore, the recording of the intracerebral activity during the stimulus paradigm gives us confidence in the specificity of our responses by providing the possibility to detect diffusing AD. It has been demonstrated that no significant cerebral blood flow change occurs during direct electrical cortical stimulation carried out with our paradigm of stimulation in the absence of AD (Kahane et al., 1999
). As most of the responses reported in this study were obtained in this condition, one can assume that the spatial resolution of our functional mapping is not blurred by some remote effects of the stimulation on neighbouring structures. This assumption seems also acceptable for responses associated with a localized AD which remained confined to the stimulation site. Conversely, responses associated with a diffusing AD were discarded from our functional mapping study. In summary, according to the above considerations, pain and non-painful somaesthetic evoked responses obtained in this study can be reliably considered as specific of the stimulation of the posterior part of the insular cortex.
Pain Representation
Apart from two patients we already reported (Ostrowsky et al., 2000), truly painful responses have not been previously described during stimulation of any area of the cerebral cortex in humans. This can be attributed to different reasons: (i) studies of insular stimulation in monkeys and dogs were performed under anaesthesia (Kaada et al., 1949
; Babkin and Van Buren, 1951
; Hoffman and Rasmussen, 1953
) thus precluding any study of pain-evoked responses. (ii) In humans, Penfield and co-workers extensively stimulated all cortical areas of the human brain, using surface electrodes, during cortectomies under local anaesthesia (Penfield and Brodley, 1937
; Penfield and Jasper, 1954
), including the insular cortex (Penfield and Faulk, 1955
). However, they only explored the upper posterior part of the insula in rare cases after removal of the fronto-parietal oper-culum. As can be seen in our results, painful sensations could not be elicited from all sites situated in the upper posterior part of the insular cortex and a large number of stimulation sites in this area must therefore be sampled in order to disclose the insular pain representation.
The existence of a pain representation in the posterior insular cortex is coherent with anatomical connectivity and electro-physiological properties of this area in monkeys. Indeed, a major source of insular inputs originates from thalamic nuclei receiving spino-thalamic-tract fibres (STT) which carry nociceptive information (Burton and Jones, 1976; Mufson and Mesulam, 1984
; Friedman and Murray, 1986
; Apkarian and Hodge, 1989
; Hodge and Apkarian, 1990
). Furthermore, Burton and Jones showed a preferential thalamic input to the posterior part of the insular cortex from the suprageniculate-limitans nucleus (SG-Li) and the posterior complex (Po) in monkeys (Burton and Jones, 1976
). In humans, Craig et al. described a thalamic structure specifically relaying painful and thermal stimuli: the posterior portion of the ventral medial nucleus, i.e. the VMpo (Craig et al., 1994
). As the latter nucleus is embedded in the Po, one can assume that its efferent fibres terminate in a similar insular area. These connections have moreover been described by Craig (Craig, 1995
), who showed tracing studies indicating the ana-tomical projection of the VMpo to the same part of the insular cortex associated in this study with pain and cold sensations. The ventral posterior inferior nucleus (VPI) is another relevant structure since it contains a high proportion of nociceptive neurons (Apkarian and Shi, 1994
) and also projects to the posterior part of the insula (Burton and Jones, 1976
; Mufson and Mesulam, 1984
). Finally, and in agreement with all these possible inputs, single-unit recordings performed in monkeys have revealed nociceptive responses in neurons of the posterior part of the insular cortex (Robinson and Burton, 1980
).
In humans, our results can be compared with previous clinical observations and studies using different techniques: evoked potential, positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Brain injuries located in the superior/posterior portion of the insula have led to im-pairment in pain perception (Greenspan and Winfield, 1992; Schmahmann and Leifer, 1992
; Greenspan et al., 1999
). In healthy volunteers, all dipolar source models of the earliest lateralized evoked potential to CO2 laser stimulation include bilateral sources in SII or the insular cortex (Tarkka and Treede, 1993
; Bromm and Chen, 1995
; Kakigi et al., 1995
; Valeriani et al., 2000
; Opsommer et al., 2001). Although these results are in rough agreement with ours, further more accurate comparisons are impeded by the limited spatial resolution of this technique.
Most PET studies reveal a bilateral activation of the insular cortex during peripheral painful stimuli. Since most of our responses were contralateral to the cortical stimulation we will only consider contralateral insular PET activation. When the mean coordinates of the insular sites eliciting painful sensations are compared with those obtained in PET studies, they are significantly different in each spatial dimension (Student's t-test; two-tailed P < 0.006). In the x (lateralmedial) and z (vertical) dimensions, the mean PET coordinates depart from ours by 5.8 mm and 6.7 mm, respectively (see Tables 1 and 3, and Fig. 4B
). This could be due to the simultaneous activation of SII which is difficult to discriminate from that of the insula using PET technique allowing no more than a 4 mm spatial resolution with the most advanced tomographs. Thus, the significance of the statistical difference obtained for these two dimensions remains highly questionable. In the y (rostro-caudal) dimension, the difference increases to 15.2 mm (see Tables 1 and 3
, and Fig. 4B
). Even if some of the earliest PET studies were performed with a spatial resolution of ~8 mm, this difference could be considered as truly significant. However, recent PET studies (Craig et al., 1996
; Xu et al., 1997
; Paulson et al., 1998
; Casey et al., 2001
) are more and more showing two separate foci of maximal activation within the insular cortex: one located in its anteroinferior part, the other in its postero-superior extent (Table 4
). Thus, not discriminating these two peaks of activation would lead to a biased mean y value shifted anteriorly with respect to our data. To overcome this bias, one can consider only the mean coordinates of the posterior peak of activation of these recent PET studies (x = 36.2 ± 2.5 mm, y = 13 ± 7 mm, z = 7 ± 7 mm, Table 4
). Doing this, the coordinate differences between the posterior peak of PET activation and our sites of stimulations for x, y and z are 5, 3.5 and 6.2 mm, respectively. According to the technical limitations already mentioned, one can consider that these differences are not significant. Furthermore, a recent study (Casey et al., 2001) has demonstrated that the pattern of structures activated by a persistent thermal nociceptive stimulus could evolve in time with respect to the beginning of the stimulation. In the early period (060 s), an anterior insular activation was observed (y = 23 mm) while two more caudal peaks of activation appear during following scans (y = 1 mm and 15 mm, respectively). This phenomenon could also explain the discrepancies along the rostro-caudal axis of data reported in previous PET studies. Also worth noting is the comparison made by Casey's group between their results obtained with a conventional protocol in 1994 and those obtained in the late phase of the nociceptive stimulation in their more recent study. In very similar stimulus conditions, a difference of 18 mm in the antero-posterior dimension stands between the two activated peaks in the contralateral insula [see table 3
in Casey et al. (Casey et al., 2001
)]. For all the above reasons, one can consider that comparisons between our data and those obtained by the PET technique is at this time very questionable.
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Finally, the more recent introduction of fMRI with its improved spatial resolution could have led to a more precise topographic location of activated brain structures. To this date, only a few studies in the field of pain processing are available (Antognini et al., 1997; Davis et al., 1998a
,b
; Disbrow et al., 1998
; Oshiro et al., 1998
; Bushnell et al., 1999
; Gelnar et al., 1999
; Ploghaus et al., 1999
; Kwan et al., 2000
; Moulton et al., 2000). Three of them deserve special attention since they directly addressed the question we are interested in. Gelnar et al. who, unfortunately, did not explore the anterior part of the insula, reported an activated peak in its posterior part, mean coordinates of which (x = 42 mm, y = 10 mm, z = 14 mm) are in fairly good agreement with our data (Gelnar et al., 1999
). Results obtained by Davis et al. are more puzzling, showing a large interindividual variability in activated insular areas which are distributed throughout its rostro-caudal axis with some preponderance in its anterior part (Davis et al., 1998b
). A similar result is obtained by Ploghaus et al. who, in addition, found a distinct peak of activation in the anterior insular cortex spe-cifically related to the expectation of painful stimuli (Ploghaus et al., 1999
). Together with our data, this last observation tends to attribute to the anterior insula a functional role not directly related to pain perception.
Non-painful Sensation Representation
It is generally accepted that tactile sensation is supported by the medial lemniscal system. However, according to its known connectivity, the ventral posterior lateral nucleus which receives its major input from the medial lemniscal tract does not project to the insular cortex in monkeys (Burton and Jones, 1976). The sensations we obtained in the posterior part of the insular cortex can nonetheless be divided into two types. Thermal ones (mainly warm) can be explained in the light of recent studies describing a STT component coding specifically not only for painful but also for thermal stimuli. It originates in the superficial lamina I of the spinal dorsal horn and terminates in a subdivision of the Po, the VMpo (Craig et al., 1994
; Dostrovsky and Craig, 1996
; Blomqvist et al., 2000
). The projections of the latter nucleus on the posterior part of the insula (Burton and Jones, 1976
) should thus ensure a thermal representation within the insula which can be activated by direct electrical stimulation. Similar con-siderations can account for the tingling sensations we observed. It has been demonstrated that wide dynamic range neurons located deeper in the dorsal horn (laminae IIIIV) are able to carry tactile information beside pain related signals (Zhang et al., 1991
). The STT recipient nuclei (Po, SG-Li, VPI) are thus able to supply the insula with non-nociceptive somaesthetic information through the limited but consistent proportion of wide-dynamic neurons they contain (Apkarian and Shi, 1994
). This is supported by single-cell studies in monkeys showing a high percentage (nearly two-thirds) of neurons in the posterior insula responding to non-nociceptive stimulations (Robinson and Burton, 1980
; Schneider et al., 1993
). The above consider-ations refer to the most direct route for non-painful stimuli to the insular cortex. However we cannot exclude that somaesthetic inputs reach the insular cortex via area SII, which sends direct projections to the posterior insular cortex (Mufson and Mesulam, 1982
) and responds to non-painful stimulation of the median nerve in humans (Frot and Mauguière, 1999
).
The non-painful representation we obtained can also be compared in terms of location with previous studies in humans using different techniques. Dipolar source modelling of somato-sensory evoked potentials in humans have revealed dipoles, deep in the upper bank of the Sylvian fissure, posterior to the central fissure, compatible with generators in SII or the insular cortex (Baumgartner et al., 1991; Hari et al., 1993
; Forss et al., 1996; Mauguière et al., 1997
). Unfortunately, the limited spatial resolu-tion of this technique does not allow more precise comparisons. Cerebral blood flow increases in the insular cortex contralateral to innocuous somaesthetic stimulation have been reported in PET studies (Burton et al., 1993
; Coghill et al., 1994
; Craig et al., 1996
, 2000
; Derbyshire et al., 1997
; Iadarola et al., 1998
) but with mean coordinates of activation peaks significantly more rostral (16.9 mm; Student's t-test: two-tailed P = 0.0007) and lateral (4 mm; Student's t-test: two-tailed P = 0.003) than mean coordinates of sites where non-painful somaesthetic sensations were evoked in our patients (see Tables 2 and 5
, and Fig. 4B
). Although statistically significant, these differences remain highly questionable for the technical reasons already evoked for the insular pain representation. More puzzling is the fact that the non-painful somaesthetic area activated in PET studies was sampled in our study and no corresponding sensations were herein evoked. Looking carefully at the data previously obtained with the PET technique [see fig. 1
of Craig et al. (Craig et al., 1996
) for 20 and 40°C thermal stimuli], it seems that the global insular activation can be constituted of two distinct peaks of activation, similar to the ones induced by painful stimuli. However, the same group, in a later study carried out in very similar stimulation conditions (Craig et al., 2000
), did not confirm this pattern at least for the 20°C stimulus, mentioning only a posterior insular peak of activation, coordinates of which are in perfect agreement with our results. On the ipsilateral side of stimulation, an anterior peak of activation that was not present in the earlier study (Craig et al., 1996
) was this time observed. Facing such data variability implies that we should show caution in more precise comparisons with our results. Finally, fMRI studies (Davis et al., 1998b
; Gelnar et al., 1999
; Disbrow et al., 2000
; Sawamoto et al., 2000
) do not allow direct comparisons since none of them gives the mean coordinates of an insular area activated by non-painful somaesthetic stimuli. Nevertheless, it is worth noting the distribution of responses following tactile stimuli reported by Davis et al. and found selectively in the posterior part of the insula, a location which tightly fits with our results (Davis et al., 1998b
). However, in the same study, innocuous temperature-related activations in the insula were not segregated consistently in any particular region.
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Another original contribution of this study concerns a possible somatotopic organization of pain representation in the human insula. To our knowledge, this question has not been addressed before in single-cell studies in monkeys (Robinson and Burton, 1980), and only once in a PET study which failed to demonstrate distinct representations for hand and foot painful stimulation (Xu et al., 1997
). Concerning the non-painful somaesthetic representation, no precise topography within the insular cortex can be found in Wieser's data (Wieser, 1983
) whereas Penfield and Faulk (Penfield and Faulk, 1955
) already noticed some somatotopic organization within the insular cortex with responses located to the limbs (and usually better lateralized) when stimulating insular sites located posteriorly and to the midline structures (lips, tongue, mouth and throat) when stimulating insular sites located more anteriorly. A similar trend is observed in our study.
Overlap Between Painful and Non-painful Representations
As can be seen in Figure 4B, insular areas where painful and non-painful somaesthetic responses were obtained, overlap. This is in agreement with the connectivity described above allowing somaesthetic inputs, whether painful or not, to converge to the posterior part of the insular cortex via direct STT-thalamo-cortical projections. At the cellular level, Robinson and Burton showed that the same insular neuron in the posterior insula was able to respond to both painful and non-painful somaesthetic stimuli (Robinson and Burton, 1980
). The receptive fields of these insular neurons were found to be large, in agreement with our observations that responses obtained when stimulating the posterior part of the insular cortex included extensive parts of the body. This is an additional factor which could participate in the overlap between the representation of the two somaesthetic modalities. Finally, PET data showing similar activated regions in the insular cortex during painful and non-painful somaesthetic stimuli (Coghill et al., 1994
; Craig et al., 1996
; Derbyshire et al., 1997
; Iadarola et al., 1998
) are coherent with this overlapping location of the pain and non-painful somaesthetic representa-tions within the human insular cortex.
Lateralization of the Painful Representation
Whereas non-painful somaesthetic sensations were evoked in similar proportion by stimulation of right or left insular sites, pain was mostly elicited when stimulating the insula of the non-dominant language and/or manual hemisphere, i.e. the right insular cortex. Previous authors have also mentioned some asym-metrical features concerning the human insula. Thus, Clarke found that the volume of the left insula was larger than that of the right (Clarke, 1896). Later, Oppenheimer et al. demonstrated, a right-sided dominance of sympathetic effects (increased cardiac frequency and blood pressure) after insular cortex stimulation as opposed to a left-sided dominance for parasympathetic effects (Oppenheimer et al., 1992). The right-sided dominance of sites where painful sensations were evoked in our study would be therefore physiologically coherent, a sympathetic tone increase being expected during painful sensations. A right hemispheric dominance has also been described in PET studies for the affectiveemotional component of pain with a preferential increased cerebral blood flow in the right anterior cingulate gyrus (Hsieh et al., 1995a
, 1996
, 1999
). Furthermore, studies on cerebral lateralization have emphasized the fact that the right hemisphere is more involved in spatial as well as in atten-tional process and many aspects of emotion (Mesulam, 1981
; Silberman and Weingartner, 1986
; Gainotti, 1996
). Attentional process and visuo-spatial integration for directing the indi-vidual's attention towards threatening external stimuli are of great importance for survival. Finally, the precocious and faster development of the right hemisphere during fetal life accounts for what is referred to as the right hemisphere conservatism (Geschwind and Galaburda, 1985
). Our data are in line with this theory, suggesting that pain integration, which is a determinant factor in species survival, could be preferentially dependent on the right hemisphere.
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Acknowledgments |
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References |
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