How the pain of others enhances our pain: searching the cerebral correlates of 'compassional hyperalgesia'.

Observing other people's pain increases our own reports to painful stimuli, a phenomenon that can be defined as 'compassional hyperalgesia' (CH). This functional magnetic resonance imaging study examined the neural correlates of CH, and whether CH could emerge when exposure to the driving stimulus was subliminal. Subjects received electric somatosensory stimuli while observing images of people undergoing painful or enjoyable somatic sensations, presented during a period allowing or not allowing conscious perception. The intensity attributed to painful stimuli increased significantly when these were delivered close to images showing human pain, but only when such images were consciously perceived. The basic core of the Pain Matrix (SI, SII, insula, mid-anterior cingulate) was activated by painful stimuli, but its activation magnitude did not increase during CH. Compassional hyperalgesia was associated with increased activity in polymodal areas involved in emotional tuning (anterior prefrontal, pregenual cingulated) and areas involved in multisensory integration and short-term memory (dorsolateral prefrontal, temporo-parieto-occipital junction). CH appears as a high-order phenomenon needing conscious appraisal of the eliciting visual stimulus, and supported by polymodal areas distinct from the basic Pain Matrix. This suggests that compassion to pain does not result from a mere 'sensory resonance' in pain networks, but rather from an interaction between the output of a first-line processing in the Pain Matrix, and the activity of a high-order network involving multisensory integration (temporo-parietal), encoding of internal states (mid-prefrontal) and short-time memory encoding (dorsolateral prefrontal). The Pain Matrix cannot be considered as an 'objective' correlate of the pain experience in all situations.

Brain generators of laser-evoked potentials: from dipoles to functional significance.

In this work we review data on cortical generators of laser-evoked potentials (LEPs) in humans, as inferred from dipolar modelling of scalp EEG/MEG results, as well as from intracranial data recorded with subdural grids or intracortical electrodes. The cortical regions most consistently tagged as sources of scalp LERs are the suprasylvian region (parietal operculum, SII) and the anterior cingulate cortex (ACC). Variability in opercular sources across studies appear mainly in the anterior-posterior direction, where sources tend to follow the axis of the Sylvian fissure. As compared with parasylvian activation described in functional pain imaging studies, LEP opercular sources tended to cluster at more superior sites and not to involve the insula. The existence of suprasylvian opercular LEPs has been confirmed by both epicortical (subdural) and intracortical recordings. In dipole-modelling studies, these sources appear to become active less than 150 ms post-stimulus, and remain in action for longer than opercular responses recorded intracortically, thus suggesting that modelled opercular dipoles reflect a "lumped" activation of several sources in the suprasylvian region, including both the operculum and the insula. Participation of SI sources to explain LEP scalp distribution remains controversial, but evidence is emerging that both SI and opercular sources may be concomitantly activated by laser pulses, with very similar time courses. Should these data be confirmed, it would suggest that a parallel processing in SI and SII has remained functional in humans for noxious inputs, whereas hierarchical processing from SI toward SII has emerged for other somatosensory sub-modalities. The ACC has been described as a source of LEPs by virtually all EEG studies so far, with activation times roughly corresponding to scalp P2. Activation is generally confined to area 24 in the caudal ACC, and has been confirmed by subdural and intracortical recordings. The inability of most MEG studies to disclose such ACC activity may be due to the radial orientation of ACC currents relative to scalp. ACC dipole sources have been consistently located between the VAC and VPC lines of Talairach's space, near to the cingulate subsections activated by motor tasks involving control of the hand. Together with the fact that scalp activities at this latency are very sensitive to arousal and attention, this supports the hypothesis that laser-evoked ACC activity may underlie orienting reactions tightly coupled with limb withdrawal (or control of withdrawal). With much less consistency than the above-mentioned areas, posterior parietal, medial temporal and anterior insular regions have been occasionally tagged as possible contributors to LEPs. Dipoles ascribed to medial temporal lobe may be in some cases re-interpreted as being located at or near the insular cortex. This would make sense as the insular region has been shown to respond to thermal pain stimuli in both functional imaging and intracranial EEG studies.

Role of operculoinsular cortices in human pain processing: converging evidence from PET, fMRI, dipole modeling, and intracerebral recordings of evoked potentials.

Insular and SII cortices have been consistently shown by PET, fMRI, EPs, and MEG techniques to be activated bilaterally by a nociceptive stimulation. The aim of the present study was to refer to, and to compare within a common stereotactic space, the nociceptive responses obtained in humans by (i) PET, (ii) fMRI, (iii) dipole modeling of scalp LEPs, and (iv) intracerebral recordings of LEPs. PET, fMRI, and scalp LEPs were obtained from normal subjects during thermal pain. Operculoinsular LEPs were obtained from 13 patients using deep brain electrodes implanted for presurgical evaluation of drug-resistant epilepsy. Whatever the technique, we obtained responses which were located bilaterally in the insular and SII cortices. In electrophysiological responses (LEPs) the SII insular contribution peaked between 150 and 250 ms poststimulus and corresponded to the earliest portions of the whole cerebral response. Group analysis of PET and fMRI data showed highly consistent responses contralateral to stimulation. On single-subject analysis, LEPs and fMRI activations were concentrated in relatively restricted volumes even though spatial sampling was quite different for both techniques. Despite our multimodal approach, however, it was not possible to separate insular from SII activities. Individual variations in the anatomy and function of SII and insular cortices may explain this limitation. This multimodal study provides, however, cross-validated spatial and temporal information on the pain-related processes occurring in the operculoinsular region, which thus appears as a major site for the early cortical pain encoding in the human brain.

Early secondary somatosensory area (SII) SEPs. Data from intracerebral recordings in humans.

OBJECTIVE: To record somatosensory evoked potentials (SEPs) to median nerve stimulation by chronically implanted electrodes in the parieto-rolandic opercular area of 9 epileptic patients, in order to evaluate whether somatosensory evoked responses could be generated in the second somatosensory area (SII) earlier than 40 ms after stimulus. METHODS: Nine patients (4 males, 5 females) with drug-resistant partial epileptic seizures were investigated using stereotactically implanted electrodes in the parietal cortex, posterior to vertical anterior commissure plane and in the frontal opercular region rostral to vertical anterior commissure (VAC). RESULTS: The main finding of this study is the recording of an early somatosensory evoked potential, (N30op), by chronically implanted electrodes in the SII area of 8 epileptic patients. In 3 patients where SEPs were performed after ipsilateral median nerve (MN) stimulation, a N30op was recorded 5.8+/-2 ms later than contralateral one. CONCLUSIONS: This is the first report of early SEPs recorded by electrodes implanted in SII area. The N30op potential, even if less consistent than later potentials, confirmed the important role of the SII area in the early processing of somatosensory inputs.

Distinct fronto-central N60 and supra-sylvian N70 middle-latency components of the median nerve SEPs as assessed by scalp topographic analysis, dipolar source modelling and depth recordings.

OBJECTIVES: To investigate the possible contribution of the second somatosensory (SII) area in the generation of the N60 somatosensory evoked potential (SEP). METHODS: In 7 epileptic patients and in 6 healthy subjects scalp SEPs were recorded by 19 electrodes placed according to the 10-20 system. All epileptic patients but one were also investigated using depth electrodes chronically implanted in the parieto-rolandic opercular cortex. Scalp SEPs underwent brain electrical source analysis. RESULTS: In both epileptic patients and healthy subjects, scalp recordings showed two middle-latency components clearly distinguishable on the basis of latency and scalp distribution: a fronto-central N60 potential contralateral to stimulation and a later bilateral temporal N70 response. SEP dipolar source modelling showed that a contralateral perisylvian dipole was activated in the scalp N70 latency range whereas separate perirolandic and frontal sources were activated at the scalp N60 latency. Depth electrodes recorded a biphasic N60/P90 response in the parieto-rolandic opercular regions contra- and ipsilateral to stimulation. CONCLUSIONS: Two different middle-latency SEP components N60 and N70 can be distinguished by topographic analysis and source modelling of scalp recordings, the sources of which are located in the fronto-central cortex contralateral to stimulation and in the supra-sylvian cortex on both sides, respectively. The source location of the scalp N70 in the SII area is strongly supported by its spatio-temporal similarities with SEPs directly recorded in the supra-sylvian opercular cortex.

Stereotactic recordings of median nerve somatosensory-evoked potentials in the human pre-supplementary motor area.

Median nerve somatosensory-evoked potentials (SEPs) have been recorded using intracortical electrodes stereotactically implanted in the frontal lobe of eight epileptic patients in order to assess the waveforms, latencies and surface-to-depth distributions of somatosensory responses generated in the anterior subdivision of supplementary motor areas (SMAs), the so-called pre-SMA. Intracortical responses were analysed in two latency ranges: 0--50 ms and 50--150 ms after stimulus. In all patients, we recorded in the first 50 ms after stimulus two positive P14 and P20 potentials followed by a N30 negativity. In the hemisphere contralateral to stimulation, the P20--N30 potentials showed a clear amplitude decrease from the outer to the inner aspect of the frontal lobe with minimal amplitudes in the pre-SMA. In the hemisphere ipsilateral to stimulus, P20 and N30 amplitudes were decreasing from mesial to lateral frontal cortex. In the 50--150 ms latency range, contacts implanted in the pre-SMA recorded a negative potential in the 60--70 ms latency range which, in five patients, was followed by a positive response peaking 80--110 ms after stimulus. These potentials were not picked up by more superficial contacts. We conclude that no early SEP is generated in pre-SMA in the first 50 ms after stimulation, while some potentials peaking in the 60--100 ms after stimulus are likely to originate from this cortical area. The latency of the pre-SMA responses recorded in our patients supports the hypothesis that the pre-SMA does not receive short-latency somatosensory inputs via direct thalamocortical projections. More probably the pre-SMA receives somatosensory inputs mediated by a polysynaptic transcortical transmission through functionally secondary motor and somatosensory areas.

Timing and spatial distribution of somatosensory responses recorded in the upper bank of the sylvian fissure (SII area) in humans.

We studied responses of the parieto-frontal opercular cortex to electric stimuli, as recorded by intra-cortical electrodes during stereotactic EEG presurgical assessment of patients with drug-resistant temporal lobe epilepsy. After electrical stimulation of the median nerve at the wrist, we consistently recorded a negative-positive biphasic response peaking at 60 ms (N60) and 90 ms (P90) post-stimulus in the upper bank of the sylvian fissure contralateral to stimulation. Talairach stereotactic coordinates of the electrode contacts recording these responses covered the pre- and post-rolandic part of the upper bank of the sylvian fissure (25

[Operculo-insular responses to nociceptive skin stimulation in humans. A review of the literature]. / Les réponses operculo-insulaires aux stimulations cutanées nociceptives chez l'homme. Revue de la littérature et données récentes.

CO2 laser stimulation selectively activates the endings of small myelinated A delta fibers, involved with non-myelinated C fibers in the processing of nociceptive information. Thus, potentials evoked by CO2 laser stimulation reflect the activation of cortical areas receiving inputs from the spinothalamic tract. In this article we review data on the early pain-related CO2 laser evoked potentials recorded on the scalp, or by intracortical electrodes, during presurgical assessment of patients with drug-resistant epilepsy. A combination of surface and depth recordings allows the description of early cortical pain responses in terms of latency, polarity and scalp topography. Such a technique also allows the localization of the anatomical generators of these early responses using dipolar source modeling of scalp-recorded evoked potentials, or intracortical recordings, in stereotactical conditions. The earliest response recorded on the scalp to CO2 laser stimulation was an N1-P1 dipolar potential field at a latency of 140-200 ms. The N1 and P1 maximal voltages are recorded in the temporal region contralateral to stimulation and mid-frontal region, respectively. Intracerebral electrodes record an activation of a dipolar cortical source in the same latency range located in the upper bank of the sylvian fissure, corresponding to the second somatosensory (SII) area ipsi- and contralateral to the stimulation and insular cortex. The SII-insular responses ipsilateral to stimulation are likely to be triggered via transcallosal fibers coming from the opposite SII area. The operculo-insular cortex contralateral to stimulation, activated through direct thalamocortical projections, is likely to represent the first step in the cortical processing of peripheral A delta fiber pain inputs.

Intracortical recordings of early pain-related CO2-laser evoked potentials in the human second somatosensory (SII) area.

We studied responses of the parieto-frontal opercular cortex to CO2-laser stimulation of A delta fiber endings, as recorded by intra-cortical electrodes during stereotactic-EEG (SEEG) presurgical assessment of patients with drug-resistant temporal lobe epilepsy. After CO2-laser stimulation of the skin at the dorsum of the hand, we consistently recorded in the upper bank of the sylvian fissure contralateral to stimulation, a negative response at a latency of 135 +/- 18 ms (N140), followed by a positivity peaking around 171 +/- 22 ms (P170). The stereotactic coordinates in the Talairach's atlas of the electrode contacts recording these early responses covered the pre- and post-rolandic part of the upper bank of the sylvian fissure (-27 < y < +12 mm; 31 < x < 57 mm; 4 < z < 23 mm), corresponding to the accepted localization of the SII area in man, possibly including the upper part of the insular cortex. The spatial distribution of these early contralateral responses in the SII-insular cortex fits wit that of the modeled sources of scalp CO2-laser evoked potentials (LEPs) and with PET data from pain activation studies. Moreover, this study showed the likely existence of dipolar sources radial to the scalp surface in SII, which are overlooked in magnetic recordings. Early responses also occurred in the SII area ipsilateral to stimulation peaking 15 ms later than in contralateral SII, suggesting a callosal transmission of nociceptive inputs between the two SII areas. Other pain responsive areas such as the anterior cingulate gyrus, the amygdala and the orbitofrontal cortex did not show early LEPs in the 200 ms post-stimulus. These findings suggest that activation of SII area contralateral to stimulation, possibly through direct thalamocortical projections, represents the first step in the cortical processing of peripheral A delta fiber pain inputs.