Maud Frot

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 Talairachs 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.

Parallel Processing of Nociceptive A-δ Inputs in SII and Midcingulate Cortex in Humans

The cingulate cortex (CC) as a part of the “medial” pain subsystem is generally assumed to be involved in the affective and/or cognitive dimensions of pain processing, which are viewed as relatively slow processes compared with the sensory-discriminative pain coding by the lateral second somatosensory area (SII)–insular cortex. The present study aimed at characterizing the location and timing of the CC evoked responses during the 1 s period after a painful laser stimulus, by exploring the whole rostrocaudal extent of this cortical area using intracortical recordings in humans. Only a restricted area in the median CC region responded to painful stimulation, namely the posterior midcingulate cortex (pMCC), the location of which is consistent with the so-called “motor CC” in monkeys. Cingulate pain responses showed two components, of which the earliest peaked at latencies similar to those obtained in SII. These data provide direct evidence that activations underlying the processing of nociceptive information can occur simultaneously in the “medial” and “lateral” subsystems. The existence of short-latency pMCC responses to pain further indicates that the “medial pain system” is not devoted exclusively to the processing of emotional information, but is also involved in fast attentional orienting and motor withdrawal responses to pain inputs. These functions are, not surprisingly, conducted in parallel with pain intensity coding and stimulus localization specifically subserved by the sensory-discriminative “lateral” pain system.

Responses of the supra-sylvian (SII) cortex in humans to painful and innocuous stimuli: A study using intra-cerebral recordings

&NA; In this study we compare the intrinsic characteristics and localization of nociceptive CO2 laser evoked potential (LEP) and non‐nociceptive electrical EP (SEP) sources recorded by deep electrodes (one to two electrodes per patient, 10–15 contacts per electrode) directly implanted in the supra‐sylvian cortex of 15 epileptic patients. Early CO2 laser (N140–P170) and electrical (N60–P90) evoked potentials were recorded by all of the electrodes implanted in the supra‐sylvian cortex contralateral to stimulation. SEPs and LEPs had similar waveforms and inter‐peak latencies. The LEPs appeared 84±15 ms later and were, on average, 14.2±22.2 &mgr;V smaller than the SEPs. These differences may be accounted for by the characteristics and the sizes of the different peripheral fibers (A&dgr; vs. A&bgr;) activated by the two types of stimuli. The stereotactic Talairach coordinates of the SEP and LEP sources covered the pre‐ and post‐rolandic upper bank of the sylvian fissure, and were not significantly different for noxious and non‐noxious stimuli. The spatial distribution of these contralateral responses fits with that of the modeled sources of scalp CO2 LEPs, magneto‐encephalographic studies, and PET data from pain and vibrotactile activation studies. These results permit us to define the SII cortex as a cortical integration area of non‐nociceptive and nociceptive inputs. This is supported by: (i) anatomical data reporting that the SII area receives inputs from both posterior columns and spino‐thalamic pathways conveying the non‐noxious and noxious information, respectively, and (ii) single cell recordings in monkeys, demonstrating that the SII area contains both nociceptive‐specific neurons and wide‐dynamic‐range neurons receiving convergent input from nociceptive and non‐nociceptive somatosensory afferents.

Thalamic thermo-algesic transmission: ventral posterior (VP) complex versus VMpo in the light of a thalamic infarct with central pain

&NA; The respective roles of the ventral posterior complex (VP) and of the more recently described VMpo (posterior part of the ventral medial nucleus) as thalamic relays for pain and temperature pathways have recently been the subject of controversy. Data we obtained in one patient after a limited left thalamic infarct bring some new insights into this debate. This patient presented sudden right‐sided hypesthesia for both lemniscal (touch, vibration, joint position) and spinothalamic (pain and temperature) modalities. He subsequently developed right‐sided central pain with allodynia. Projection of 3D magnetic resonance images onto a human thalamic atlas revealed a lesion involving the anterior two thirds of the ventral posterior lateral nucleus (VPL) and, to a lesser extent, the ventral posterior medial (VPM) and inferior (VPI) nuclei. Conversely, the lesion did not extend posterior and ventral enough to concern the putative location of the spinothalamic‐afferented nucleus VMpo. Neurophysiological studies showed a marked reduction (67%) of cortical responses depending on dorsal column‐lemniscal transmission, while spinothalamic‐specific, CO2‐laser induced cortical responses were only moderately attenuated (33%). Our results show that the VP is definitely involved in thermo‐algesic transmission in man, and that its selective lesion can lead to central pain. However, results also suggest that much of the spino‐thalamo‐cortical volley elicited by painful heat stimuli does not transit through VP, supporting the hypothesis that a non‐VP locus lying more posteriorly in the human thalamus is important for thermo‐algesic transmission.

Cortical representation of pain in primary sensory-motor areas (S1/M1)—a study using intracortical recordings in humans

Intracortical evoked potentials to nonnoxious Aβ (electrical) and noxious Aδ (laser) stimuli within the human primary somatosensory (S1) and motor (M1) areas were recorded from 71 electrode sites in 9 epileptic patients. All cortical sites responding to specific noxious inputs also responded to nonnoxious stimuli, while the reverse was not always true. Evoked responses in S1 area 3b were systematic for nonnoxious inputs, but seen in only half of cases after nociceptive stimulation. Nociceptive responses were systematically recorded when electrode tracks reached the crown of the postcentral gyrus, consistent with an origin in somatosensory areas 1–2. Sites in the precentral cortex also exhibited noxious and nonnoxious responses with phase reversals indicating a local origin in area 4 (M1). We conclude that a representation of thermal nociceptive information does exist in human S1, although to a much lesser extent than the nonnociceptive one. Notably, area 3b, which responds massively to nonnoxious Aβ activation was less involved in the processing of noxious heat. S1 and M1 responses to noxious heat occurred at latencies comparable to those observed in the supra‐sylvian opercular region of the same patients, suggesting a parallel, rather than hierarchical, processing of noxious inputs in S1, M1 and opercular cortex. This study provides the first direct evidence for a spinothalamic related input to the motor cortex in humans. Hum Brain Mapp 34:2655–2668, 2013.

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.

Evoked potentials to nociceptive stimuli delivered by CO2 or Nd:YAP lasers

OBJECTIVE This study compares the amplitude, latency, morphology, scalp topography and intracranial generators of laser-evoked potentials (LEPs) to CO(2) and Nd:YAP laser stimuli. METHODS LEPs were assessed in 11 healthy subjects (6 men, mean age 39+/-10 years) using a 32-channel acquisition system. Laser stimuli were delivered on the dorsum of both hands (intensity slightly above pain threshold), and permitted to obtain lateralised (N1) and vertex components (N2-P2) with similar scalp distribution for both types of lasers. RESULTS The N1-YAP had similar latencies but significantly higher amplitudes relative to N1-CO(2). The N2-P2 complex showed earlier latencies, higher amplitudes (N2) and more synchronised responses when using Nd:YAP stimulation. The distribution of intracranial generators assessed with source localization analyses (sLORETA) was similar for Nd:YAP and CO(2) lasers. The insular, opercular, and primary sensorimotor cortices were active during the N1 time-window, whereas the anterior midcingulate, supplementary motor areas and mid-anterior insulae were active concomitant to the N2-P2 complex. CONCLUSIONS Earlier latencies and larger amplitudes recorded when using Nd:YAP pulses suggest a more synchronized nociceptive afferent volley with this type of laser. SIGNIFICANCE This, together with its handy utilization due to optic fibre transmission, may favour the use of Nd:YAP lasers in clinical settings.

Processing of Nociceptive Input From Posterior to Anterior Insula in Humans

Previous brain imaging studies have shown robust activations in the insula during nociceptive stimulation. Most activations involve the posterior insular cortex but they can cover all insular gyri in some fMRI studies. However, little is known about the timing of activations across the different insular sub‐regions. We report on the distribution of intracerebrally recorded nociceptive laser evoked potentials (LEPs) acquired from the full extent of the insula in 44 epileptic patients. Our study shows that both posterior and anterior subdivisions of the insular cortex respond to a nociceptive heat stimulus within a 200–400 ms latency range. This nociceptive cortical potential occurs firstly, and is larger, in the posterior granular insular cortex. The presence of phase reversals in LEP components in both posterior and anterior insular regions suggests activation of distinct, presumably functionally separate, sources in the posterior and anterior parts of the insula. Our results suggest that nociceptive input is first processed in the posterior insula, where it is known to be coded in terms of intensity and anatomical location, and then conveyed to the anterior insula, where the emotional reaction to pain is elaborated. Hum Brain Mapp 35:5486–5499, 2014.

Do we activate specifically somatosensory thin fibres with the concentric planar electrode? A scalp and intracranial EEG study.

Summary We compare CE‐SEPs, Aβ SEPs, and Aδ LEPs in healthy subjects and patients and conclude that there is a lack of nociceptive specificity of the concentric planar electrode. ABSTRACT Laser‐evoked potentials (LEPs) are acknowledged as the most reliable laboratory tool for assessing thermal and pain pathways. Electrical stimulation with a newly developed planar concentric electrode, delivering stimuli limited to the superficial skin layers, has been suggested to provide selective activation of Aδ fibres without the inconveniences linked to laser stimulation. The aim of our study was to compare the scalp and intracranial responses to planar concentric electrode stimulation (CE‐SEPs) with those of LEPs and standard somatosensory‐evoked potentials (SEPs). Sixteen healthy subjects, 6 patients with intracortical electrodes, and 2 patients with selective lesions of the spinothalamic pathway were submitted to Neodymium:Yttrium‐Aluminium‐Perovskite laser stimulations, and electrical stimulations using standard electrodes or planar concentric electrodes (CE). In both healthy controls and epileptic implanted patients, CE‐ and standard SEPs showed significantly shorter latencies than LEPs. This is consistent with Aβ‐fibre activation, peripheral activation time being unable to account for longer LEP latencies. In the patients with spinothalamic lesions, LEPs were absent after stimulation of the affected territory, while CE‐SEPs were still present. For these 2 reasons, we conclude that the planar CE does not selectively activate the Aδ and C fibers, but coexcites a significant proportion of large myelinated Aβ fibres that dominate the ensuing cortical response. The use of CE‐SEPs for the detection of spinothalamic system lesions is therefore not warranted; the planar electrode can, however, represent a useful tool to study nociceptive reflexes, which can be reliably elicited even in the presence of Aβ coactivation.

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.