François Mauguière

Electrical stimulation of motor cortex for pain control: a combined PET-scan and electrophysiological study☆

Although electrical stimulation of the precentral gyrus (MCS) is emerging as a promising technique for pain control, its mechanisms of action remain obscure, and its application largely empirical. Using positron emission tomography (PET) we studied regional changes in cerebral flood flow (rCBF) in 10 patients undergoing motor cortex stimulation for pain control, seven of whom also underwent somatosensory evoked potentials and nociceptive spinal reflex recordings. The most significant MCS-related increase in rCBF concerned the ventral-lateral thalamus, probably reflecting cortico-thalamic connections from motor areas. CBF increases were also observed in medial thalamus, anterior cingulate/orbitofrontal cortex, anterior insula and upper brainstem; conversely, no significant CBF changes appeared in motor areas beneath the stimulating electrode. Somatosensory evoked potentials from SI remained stable during MCS, and no rCBF changes were observed in somatosensory cortex during the procedure. Our results suggest that descending axons, rather than apical dendrites, are primarily activated by MCS, and highlight the thalamus as the key structure mediating functional MCS effects. A model of MCS action is proposed, whereby activation of thalamic nuclei directly connected with motor and premotor cortices would entail a cascade of synaptic events in pain-related structures receiving afferents from these nuclei, including the medial thalamus, anterior cingulate and upper brainstem. MCS could influence the affective-emotional component of chronic pain by way of cingulate/orbitofrontal activation, and lead to descending inhibition of pain impulses by activation of the brainstem, also suggested by attenuation of spinal flexion reflexes. In contrast, the hypothesis of somatosensory cortex activation by MCS could not be confirmed by our results.

Clinical manifestations of insular lobe seizures: a stereo-electroencephalographic study.

Summary:  Purpose: In this study, we report the clinical features of insular lobe seizures based on data from video and stereo‐electroencephalographic (SEEG) ictal recordings and direct electric insular stimulation of the insular cortex performed in patients referred for presurgical evaluation of temporal lobe epilepsy (TLE).

Recommendations for the clinical use of somatosensory-evoked potentials.

The International Federation of Clinical Neurophysiology (IFCN) is in the process of updating its Recommendations for clinical practice published in 1999. These new recommendations dedicated to somatosensory-evoked potentials (SEPs) update the methodological aspects and general clinical applications of standard SEPs, and introduce new sections dedicated to the anatomical-functional organization of the somatosensory system and to special clinical applications, such as intraoperative monitoring, recordings in the intensive care unit, pain-related evoked potentials, and trigeminal and pudendal SEPs. Standard SEPs have gained an established role in the health system, and the special clinical applications we describe here are drawing increasing interest. However, to prove clinically useful each of them requires a dedicated knowledge, both technical and pathophysiological. In this article we give technical advice, report normative values, and discuss clinical applications.

The role of the insular cortex in temporal lobe epilepsy

The role of the insular cortex in the genesis of temporal lobe epileptic (TLE) seizures has been investigated in 21 patients with drug‐refractory TLE using chronic depth stereotactic recordings of the insular cortex activity and video recordings of ictal symptoms during 81 spontaneous electroclinical seizures. All of the recorded seizures were found to invade the insula, most often after a relay in the ipsilateral hippocampus (19/21 patients). However, 2 patients had seizures that originated in the insular cortex itself. Ictal symptoms associated with the insular discharges were similar to those usually attributed to mesial temporal lobe seizures, so that scalp video‐electroencephalographic monitoring does not permit making any difference between ictal symptoms of temporo‐mesial and insular discharges. A favorable outcome was obtained after a temporal cortectomy sparing the insular cortex in 15 of 17 operated patients. Seizures propagating to the insular cortex were found to be fully controlled by surgery, whereas those originating in the insular cortex persisted after temporal cortectomy. The fact that seizures originating in the insular cortex are not influenced by temporal lobectomy is likely to explain some of the failures of this surgical procedure in TLE. Ann Neurol 2000;48:614–623

Association and dissociation between laser-evoked potentials and pain perception

WE investigated the relation between the subjective sensation of pain and two different components of the laser evoked potential, namely the vertex response (N220-P350) and an earlier lateralized response (middle-latency NP160). Brain responses to laser stimuli were obtained in 15 subjects under attentive and distractive conditions. Although stimulus intensity was kept constant, it was perceived as significantly higher when subjects attended the stimulation. There was a positive correlation between subjective intensity perception and the amplitude of the vertex potential, but no correlation existed with the middle-latency component. While laser vertex potentials may reflect attentional/perceptual mechanisms that determine subjective experience, the NP160 behaves as a pre-perceptual sensory response that should be advantageous in the assessment of early cortical pain processing.

Activation of a distributed somatosensory cortical network in the human brain. A dipole modelling study of magnetic fields evoked by median nerve stimulation. Part I: location and activation timing of SEF sources

Cortical areas responsive to somatosensory inputs were assessed by recording somatosensory evoked magnetic fields (SEF) to electrical stimulation of the left median nerve at wrist, using a 122-SQUID neuromagnetometer in various conditions of stimulus rate, attentional demand and detection task. Source modelling combined with magnetic resonance imaging (MRI) allowed localisation of six SEF sources on the outer aspect of the hemispheres located respectively: (1) in the posterior bank of the rolandic fissure (area SI), the upper bank of the sylvian fissure (parietal opercular area SII) and the banks of the intraparietal fissure contralateral to stimulation, (2) in the SII area ipsilateral to stimulation and (3) in the mid-frontal or inferior frontal gyri on both sides. All source areas were found to be simultaneously active at 70-140 ms after the stimulus, the SI source was the only one active already at 20-60 ms. The observed activation timing suggests that somatosensory input from SI is processed to higher-order areas through serial feedforward projections. However the long-lasting activations of all sources and their overlap in time is also compatible with a top-down control mediated via backward projections.

Early Amygdala Reaction to Fear Spreading in Occipital, Temporal, and Frontal Cortex: A Depth Electrode ERP Study in Human

The amygdala involvement in fear processing has been reported in behavioral, electrophysiological, and functional imaging studies. However, the literature does not provide precise data on the temporal course of facial emotional processing. Intracranial event-related potentials to facial expressions were recorded in epileptic patients implanted with depth electrodes during a presurgical evaluation. Specific potentials to fear beginning 200 ms poststimulus were observed in amygdala, both individually in two patients and in a ten patient population study. These potentials occurred 100 ms earlier than potentials to disgust recorded in insula in a previous study. Potentials to fear were confined in amygdala during a first transient period and then, during a second period of sustained activity, spread to occipito-temporal, anterior temporal, and orbitofrontal cortex in two patients. This study clarifies the temporal course of the involvement of these structures known to be part of a neural network recruited to process emotional information.

Electrical stimulation of precentral cortical area in the treatment of central pain: electrophysiological and PET study

&NA; The clinical, electrophysiological and haemodynamic effects of precentral gyrus stimulation (PGS) as a treatment of refractory post‐stroke pain were studied in 2 patients. The first patient had a right hemibody pain secondary to a left parietal infarct sparing the thalamus, while the second patient had left lower limb pain developed after a right mesencephalic infarct. In both cases, spontaneous pain was associated with hyperpathia, allodynia and hypoaesthesia in the painful territory involving both lemniscal and extra‐lemniscal sensory modalities in patient 1, extra‐lemniscal sensory modality only in patient 2. Both patients were treated with electrical PGS by means of a 4‐pole electrode, the central sulcus being per‐operatively located using the phase‐reversal of the N20 wave of somatosensory evoked potentials. No sensory side effect, abnormal movement or epileptic seizure were observed during PGS. The analgesic effects were somatotopically distributed according to the localization of electrode on motor cortex. A satisfactory long‐lasting pain control (60–70% on visual analog scale) as well as attenuation of nociceptive reflexes were obtained during PGS in the first patient. Pain relief was less marked and only transient (2 months) in patient 2, in spite of a similar operative procedure. In this patient, in whom PGS eventually evoked painful dysesthesiae, no attenuation of nociceptive RIII reflex could be evidenced during PGS. Cerebral blood flow (CBF) was studied using positron emission tomography (PET) with 15O‐labeled water. The sites of CBF increase during PGS were the same in both patients, namely the thalamus ipsilateral to PGS, cingulate gyrus, orbito‐frontal cortex and brainstem. CBF increase in brainstem structures was greater and lasted longer in patient 1 while patient 2 showed a greater CBF increase in orbito‐frontal and cingular regions. Our results suggest that PGS‐induced analgesia is somatotopically mediated and does not require the integrity of somatosensory cortex and lemniscal system. PGS analgesic efficacy may be mainly related to increased synaptic activity in the thalamus and brainstem while changes in cingulate gyrus and orbito‐frontal cortex may be rather related to attentional and/or emotional processes. The inhibitory control on pain would involve thalamic and/or brainstem relays on descending pathways down to the spinal cord segments, leading to a depression of nociceptive reflexes. Painful dysesthesiae during stimulation have to be distinguished from other innocuous sensory side effects, since they may compromise PGS efficacy.

Scalp topography and dipolar source modelling of potentials evoked by CO2 laser stimulation of the hand.

CO2 laser evoked potentials to hand stimulation recorded using a scalp 19-channel montage in 11 normal subjects consistently showed early N1/P1 dipolar field distribution peaking at a mean latency of 159 ms. The N1 negativity was distributed in the temporoparietal region contralateral to stimulation and the P1 positivity in the frontal region. The N1/P1 response was followed by 3 distinct components: (1) N2a reaching its maximal amplitude at the vertex and ipsilaterally to the stimulated hand, (2) N2b mostly distributed in the frontal region, and (3) P2 with a mid-central topography. Brain electrical source analysis showed that this sequence was explained, with a residual variance below 5%, by a model including two dipoles in the upper bank of the Sylvian fissure of each hemisphere, a frontal dipole close to the midline, and two anterior medial temporal dipoles, thus suggesting a sequential activation of the two second somatosensory areas, anterior cingulate gyrus and the amygdalar nuclei or the hippocampal formations, respectively. This model fitted well with the scalp field topography of grand average responses to stimulation of left and right hand obtained across all subjects as well as when applied to individual data. Our findings suggest that the second somatosensory area contralateral to the stimulation is the first involved in the building of pain-related responses, followed by ipsilateral second somatosensory area and limbic areas receiving noxious inputs from the periphery.

Functional Mapping of the Insular Cortex: Clinical Implication in Temporal Lobe Epilepsy

Summary: Purpose: We report the results of 75 intracortical electrical stimulations of the insular cortex performed in 14 patients during stereo‐electroencephalography (SEEG) investigation of drug‐resistant partial epilepsy. The insular cortex was investigated on electroclinical arguments suggesting the possibility of a perisylvian spread or a rapid multilobar diffusion of the discharges during video EEG.