Functional mapping of the human insula: Data from electrical stimulations.

Electrical stimulations of the insula performed during stereo-electro-encephalography (SEEG) reproduce the ictal symptoms observed during the development of insular seizures and are also a unique opportunity to provide a functional mapping of the insular cortex. We provide here a functional mapping of the insular cortex obtained by electrical stimulation, based on our previous work and a review of literature. The most frequent responses to insula stimulation were somatosensory sensations followed by visceral responses. Then, in decreasing order of frequency, auditory sensations, vestibular illusions, speech impairment, gustato-olfactory sensations and motor reactions were evoked. A bipolar organization could be evidenced with a posterior part assigned to somatosensory functions and notably to pain perception; and an anterior part assigned to visceral functions. Although some degree of spatial segregation could be evidenced, there was a clear spatial overlap between the representations of the different types of responses. These data provide a better understanding of physiological insular functions, insula seizures semiology and a prediction of post-surgical deficits. Insula is the only cortical region where stimulations demonstrate such a multi-modal representation, perhaps supporting its integrative functions of polymodal inputs.

Can you guess the colour of this moving object? A dissociation between colour and motion in blindsight.

Blindsight has been primarily and extensively studied by Lawrence Weiskrantz. Residual visual abilities following a hemispheric lesion leading to homonymous hemianopia encompass a variety of visual-perceptual and visuo-motor functions. Attention blindsight produces the more salient subjective experiences, especially for motion (Riddoch phenomenon). Action blindsight illustrates visuo-motor abilities despite the patients' feeling that they produce random movements. Perception blindsight seems to be the weakest residual function observed in blindsight, e.g. for wavelength sensitivity. Discriminating motion produced by isoluminant colours does not give rise to blindsight for motion but the outcome of the reciprocal test is not known. Here we tested whether moving stimuli could give rise to colour discrimination in a patient with homonymous hemianopia. It was found that even though the patient exhibited nearly perfect performances for motion direction discrimination his colour discrimination for the same moving stimulus remained at chance level. It is concluded that easily discriminated moving stimuli do not give rise to colour discrimination and implications for the 3 levels of blindsight taxonomy are discussed.

[Electrophysiological testing in spinal cord tumors]. / Les explorations neurophysiologiques dans les tumeurs médullaires.

Evoked potentials (EPs) are useful to evaluate the functional impairment of motor and somatosensory pathways in spinal cord tumors. Conduction through pyramidal tracts is evaluated by motor EPs (MEPs) elicited by transcranial stimulation, magnetic for awake patients or electric in the operating room. Somatosensory EPs (SEPs) and laser EPs (LEPs) are complementary procedures to explore conduction in dorsal columns and spinothalamic tracts, respectively. MEPs as well as SEPs show conduction abnormalities in about 60% of cases with a sensitivity that increases up to 70% when both procedures are carried out. Abnormalities are observed in the absence of any clinical sign in respectively 7% and 15% of cases for MEPs and SEPs. Multilevel stimulations for SEPs recordings permit to detect segmental dysfunction in 70% in case of cervical TIM, even in the absence of clinical signs. LEPs are useful in specific clinical situations: they allow a dermatomal stimulation and are correlated to segmental thermoalgic anaesthesia. Electrophysiological testing plays an important role in the diagnostic and therapeutic strategy: before surgery, MEPs and SEPs objectively evaluate the functional impairment directly related to the lesion. They also help by permitting a follow-up, either before surgery when the surgical decision is delayed because of a good clinical tolerance of the lesion, or after operation to evaluate the functional evolution. Intraoperative monitoring of MEPs and SEPs allows informing the surgeon about the impact on each surgical manipulation. No prospective randomized study has been performed to date to compare clinical evolution after surgery with or without monitoring. Nevertheless, a wide consensus became established in favor of monitoring to limit the risk of postoperative definite deficit and to permit an optimal surgical resection without risk when responses are preserved.

Epileptic networks in patients with bitemporal epilepsy: the role of SEEG for the selection of good surgical candidates.

OBJECTIVE: In this study we investigated the electrical characteristics of seizures recorded by stereo-EEG (SEEG) in a cohort of patients with bitemporal lobe epilepsy (BTLE), in the attempt to verify the presence/absence of different seizure patterns and to identify good surgical candidates. METHODS: We retrospectively reviewed 14 consecutive patients with medically refractory BTLE confirmed by scalp video-EEG (VEEG) recording of bitemporal independent or non-lateralizing seizure onset. All patients had a comprehensive evaluation including history and neurologic examination, MRI, scalp VEEG and SEEG monitoring. Neuropsychological, Wada testing and FDG-PET were performed in most patients. When temporal lobe resection was performed (7 cases), the postoperative follow-up was of at least 1year. RESULTS: Intracranial EEG (SEEG) revealed that only 4/14 (29%) patients were suffering of unilateral TLE. Two groups of patients with distinct SEEG patterns of seizures were identified: a temporo-mesial origin of seizures was the only SEEG pattern observed in 8 patients (Group 1); in 6 patients seizures originated from multiple onset zones in mesial and lateral temporal cortex or from extra-temporal cortex (Group 2). All patients of group 1 (except one who refused surgery) underwent surgery and had a favorable outcome (6 Engel class I; one Engel's class II). The side of surgery was not necessarily the one responsible for the majority of recorded seizures. It was chosen on the basis of MRI findings and consistency of data from presurgical functional investigations, mostly memory assessment and Wada test. SIGNIFICANCE: In patients with suspected BTLE, SEEG proved to be useful in identifying the origin of seizures. Good surgical outcome can be obtained after unilateral resection in patients with bilateral independent seizure onsets or sequential mesial temporal involvement on SEEG if the side of surgery is chosen considering multimodal data.

Somatosensory evoked potentials in the assessment of peripheral neuropathies: Commented results of a survey among French-speaking practitioners and recommendations for practice.

BACKGROUND: Somatosensory evoked potentials (SSEPs) are increasingly performed for the assessment of peripheral neuropathies, but no practical guidelines have yet been established in this specific application. STUDY AIM: To determine the relevant indication criteria and optimal technical parameters for SSEP recording in peripheral neuropathy investigation. METHODS: A survey was conducted among the French-speaking practitioners with experience of SSEP recording in the context of peripheral neuropathies. The results of the survey were analyzed and discussed to provide recommendations for practice. RESULTS: SSEPs appear to be a second-line test when electroneuromyographic investigation is not sufficiently conclusive, providing complementary and valuable information on central and proximal peripheral conduction in the somatosensory pathways. CONCLUSIONS: Guidelines for a standardized recording protocol, including the various parameters to be measured, are proposed. CLINICAL RELEVANCE: We hope that these proposals will help to recognize the value of this technique in peripheral neuropathy assessment in clinical practice.

H.M. never again! An analysis of H.M.'s epilepsy and treatment.

On August 25, 1953, the patient H.M., aged 27, underwent a bilateral surgical destruction of the inner aspect of his temporal lobes performed by William Beecher Scoville with the aim to control H.M.'s drug refractory epileptic seizures and alleviate their impact on his quality of life. Postoperatively, H.M. presented for 55 years a "striking and totally unexpected grave loss of recent memories". This paper reports what we know about H.M.'s epilepsy before and after surgery and puts forward arguments supporting the syndromic classification of his epilepsy. We attempted to elucidate what could have been the rationale, in 1953, of Scoville's decision to carry out a bilateral ablation of H.M.'s medial temporal lobe structures, and we examined whether there was any convincing argument published before 1953 suggesting that bilateral hippocampal ablation could result in a permanent and severe amnesia. Our a posteriori analysis of H.M.'s medical history suggested that he was most probably suffering from idiopathic generalized epilepsy with absences and generalized convulsive seizures worsened by high dosage phenytoin treatment, or less probably from cryptogenic frontal lobe epilepsy. Importantly, he did not have temporal lobe epilepsy. Scoville based his proposal of bilateral mesial temporal lobe ablation on his experience as a psychosurgeon and on the assumption that the threshold of generalized epileptic activity could be lowered by some kind of hippocampal dysfunction potentially epileptic in nature. Given the scanty information on the link between amnesia and medial temporal lobe lesions that was available in humans in 1953, one can understand why Scoville was so surprised by the "striking and totally unexpected" memory loss he observed in H.M. after the bilateral ablation of his mesial temporal lobe structures.

Advanced [(18)F]FDG and [(11)C]flumazenil PET analysis for individual outcome prediction after temporal lobe epilepsy surgery for hippocampal sclerosis.

PURPOSE: We have previously shown that an imaging marker, increased periventricular [(11)C]flumazenil ([(11)C]FMZ) binding, is associated with failure to become seizure free (SF) after surgery for temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS). Here, we investigated whether increased preoperative periventricular white matter (WM) signal can be detected on clinical [(18)F]FDG-PET images. We then explored the potential of periventricular FDG WM increases, as well as whole-brain [(11)C]FMZ and [(18)F]FDG images analysed with random forest classifiers, for predicting surgery outcome. METHODS: Sixteen patients with MRI-defined HS had preoperative [(18)F]FDG and [(11)C]FMZ-PET. Fifty controls had [(18)F]FDG-PET (30), [(11)C]FMZ-PET (41), or both (21). Periventricular WM signal was analysed using Statistical Parametric Mapping (SPM8), and whole-brain image classification was performed using random forests implemented in R (http://www.r-project.org). Surgery outcome was predicted at the group and individual levels. RESULTS: At the group level, non-seizure free (NSF) versus SF patients had periventricular increases with both tracers. Against controls, NSF patients showed more prominent periventricular [(11)C]FMZ and [(18)F]FDG signal increases than SF patients. All differences were more marked for [(11)C]FMZ. For individuals, periventricular WM signal increases were seen at optimized thresholds in 5/8 NSF patients for both tracers. For SF patients, 1/8 showed periventricular signal increases for [(11)C]FMZ, and 4/8 for [(18)F]FDG. Hence, [(18)F]FDG had relatively poor sensitivity and specificity. Random forest classification accurately identified 7/8 SF and 7/8 NSF patients using [(11)C]FMZ images, but only 4/8 SF and 6/8 NSF patients with [(18)F]FDG. CONCLUSION: This study extends the association between periventricular WM increases and NSF outcome to clinical [(18)F]FDG-PET, but only at the group level. Whole-brain random forest classification increases [(11)C]FMZ-PET's performance for predicting surgery outcome.

Optimal parameters of transcranial electrical stimulation for intraoperative monitoring of motor evoked potentials of the tibialis anterior muscle during pediatric scoliosis surgery.

OBJECTIVE: Transcranial electric stimulation elicited muscle motor evoked potentials (TESmMEPs) is one of the best methods for corticospinal tract's function monitoring during spine and spinal cord surgeries. A train of multipulse electric stimulation is required for eliciting TESmMEPs under general anaesthesia. Here, we investigated the best stimulation parameters for eliciting and recording tibialis anterior's TESmMEPs during paediatric scoliosis surgery. PATIENTS AND METHODS: Numbers of pulses (NOP), inter-stimulus intervals (ISI) and current intensities allowing the best size tibialis anterior muscle's TESmMEPs under general anaesthesia, were tested and collected during 77 paediatric scoliosis surgery monitoring procedures in our hospital. Individual pulse duration was kept at 0.5 ms and stimulating electrodes were positioned at C1 and C2 (International 10-20-EEG-System) during all the tests. RESULTS: The NOP used for eliciting the best tibialis anterior TESmMEPs response was 5, 6, and 7 respectively in 21 (27%), 47 (61%) and 9 (12%) out of the 77 patients. The ISI was 2, 3 and 4 ms respectively in 13 (17%), 55 (71%) and 9 (12%) of them. The current intensity used varied from 300 to 700 V (mean: 448±136 V). CONCLUSION: Most patients had 6 as best NOP (61%) and 3 ms as best ISI (71%). These findings support that a NOP of 6 and an ISI of 3 ms should be preferentially used as optimal stimulation settings for intraoperative tibialis anterior muscle's TESmMEPs eliciting and recording during paediatric scoliosis surgery.

[Neurophysiological evaluation of cortical excitability in migraine: a review of the literature]. / Évaluation électrophysiologique de l'excitabilité corticale dans la migraine.

INTRODUCTION: Neurophysiological studies point to altered cortical neuronal excitability in migraine patients. STATE OF ART: Between attacks, migraine brain seems to be "hyperresponsive" to repetitive stimuli, as suggested by evoked potential studies that show a lack of habituation to sensory stimuli. Transcranial magnetic stimulation suggests an impairment of intracortical inhibitory circuits in migraine, especially in migraine with aura. Controversial results are obtained in migraineurs without aura. Repetitive transcranial magnetic stimulation also shows in migraine with aura a paradoxical enhancement of intracortical facilitation by low frequency stimulation and greater increased facilitatory mechanisms by high-frequency stimulation. Importantly, cortical excitability level fluctuates over time in relation to the migraine cycle. The interictal lack of habituation to sensory stimuli normalizes before and during a migraine attack. Changes of cortical excitability consistent with the theory of cortical spreading depression are also observed during migraine aura with magnetoencephalography. PERSPECTIVES: The exact role of cortical excitability changes in migraine pathophysiology and possibly in chronic migraine is still unknown. Further studies are also necessary to clarify the role of migraine preventive drugs on brain excitability. CONCLUSIONS: In this review, the results of neurophysiological studies conducted in migraine patients will be described and the associated pathophysiological hypotheses will be discussed.

Bond breaking in a Morse chain under tension: fragmentation patterns, higher index saddles, and bond healing.

We investigate the fragmentation dynamics of an atomic chain under tensile stress. We have classified the location, stability type (indices), and energy of all equilibria for the general n-particle chain, and have highlighted the importance of saddle points with index >1. We show that for an n = 2-particle chain under tensile stress the index 2 saddle plays a central role in organizing the dynamics. We apply normal form theory to analyze phase space structure and dynamics in a neighborhood of the index 2 saddle. We define a phase dividing surface (DS) that enables us to classify trajectories passing through a neighborhood of the saddle point using the values of the integrals associated with the normal form. We also generalize our definition of the dividing surface and define an extended dividing surface (EDS), which is used to sample and classify all trajectories that pass through a phase space neighborhood of the index 2 saddle at total energies less than that of the saddle. Classical trajectory simulations are used to study fragmentation patterns for the n = 2 chain under tension. That is, we investigate the relative probability for breaking one bond versus concerted fission of several (two, in this case) bonds. Initial conditions for trajectories are obtained by sampling the EDS at constant energy. We sample trajectories at fixed energies both above and below the energy of the saddle. The fate of trajectories (single versus multiple bond breakage) is explored as a function of the location of the initial condition on the EDS, and a connection made to the work of Chesnavich on collision-induced dissociation. A significant finding is that we can readily identify trajectories that exhibit bond healing. Such trajectories pass outside the nominal (index 1) transition state for single bond dissociation, but return to the potential well region, possibly several times, before ultimately dissociating.

[Natural history of adult-onset eIF2B-related disorders: a multicentric survey of 24 cases]. / Histoire naturelle des leucodystrophies avec mutation EIF2B: étude rétrospective multicentrique de 24 cas adultes.

INTRODUCTION: The childhood ataxia with central nervous system hypomyelination-vanishing white matter syndrome (CACH-VWM) was first characterized in children (2-5 years) on clinical and MRI criteria: cerebellospastic signs associated with episodes of rapid deterioration following stress and extensive cavitatingleucoencephalopathy. Causative mutations were found in the five genes encoding the subunits of the eukaryotic initiation factor 2B (eIF2B), involved in protein synthesis and its regulation under cellular stresses. A broad clinical spectrum has been subsequently described from congenital to adult-onset forms leading to the concept of eIF2B-related disorders. Our aim was to describe clinical and brain magnetic resonance imaging characteristics, genetic findings and natural history of patients with adult-onset eIF2B-related disorders. METHODS: The inclusion criteria were based on the presence of EIF2B mutations and a disease onset after the age of 16 years. One patient with an asymptomatic diagnosis was also included. Clinical and MRI findings were retrospectively recorded in all patients. This multicentric study included 24 patients from 22 families. RESULTS: A sex-ratio imbalance was noted (male/female=5/19). The mean age of onset was 30 years (range 12-62). Initial symptoms were neurologic (n=20), psychiatric (n=3) and ovarian failure (n=6). During follow-up (mean: 11 years, range 2-35 years), two patients died. Of the 22 survivors, 67% showed a decline in their cognitive functions and mean EDSS was 5.6 (range=0-9.5). One case remained asymptomatic. Stress worsened clinical symptoms in 33% of the patients. Magnetic resonance imaging findings consisted of cerebral atrophy (92%), extensive cystic leucoencephalopathy (83%), corpus callosum involvement (92%) and cerebellar (37%) T2-weighted hyperintensities. Most patients (83%) showed mutations in the EIF2B5 gene. The recurrent p.Arg113His-eIF2Be mutation was found at a homozygous state in 58% of the 24 eIF2B-mutated patients. CONCLUSION: eIF2B-related disorder is probably underestimated as an adult-onset inherited leucoencephalopathy. Cerebral atrophy is constant, whereas the typical vanishing of the white matter can be absent. Functional and cognitive prognosis remains severe. Molecular diagnosis is facilitated for these forms by screening for the recurrent p.Arg113His-eIF2Be mutation.

Evoked potential study of hippocampal efferent projections in the human brain.

OBJECTIVE: To explore in human potential hippocampal projections within and outside the temporal lobe. METHODS: We performed intra-cerebral electrical stimulations in seven patients investigated by depth electrodes for refractory epilepsy and analyzed the presence of evoked potentials (EPs) in all brain regions explored. Bipolar electrical stimulations, consisting of two series of 25 pulses of 1 ms duration, 0.2 Hz frequency, and 3 mA intensity, were delivered in a total of 36 hippocampal stimulations sites. RESULTS: Reproducible EPs were recorded in several brain regions with variable latencies, amplitudes and morphologies. Within the temporal lobe, EPs were present in the amygdala, entorhinal cortex, temporal pole and temporal neocortex. EPs were also observed in the frontal lobe, anterior cingulate gyrus and orbito-frontal cortex, midcingulate and posterior cingulate gyrus, insula and thalamic pulvinar nucleus. CONCLUSION: Our results demonstrate a large distribution of direct or indirect hippocampal projections. SIGNIFICANCE: This widespread connectivity supports the previous definition of different networks involved mainly in memory and behavioral processes, implicating the temporal lobe, the cingulate gyrus or the prefrontal region. Our data provide some clues to further evaluate potential pathways of propagation of mesial temporal lobe seizure, via the insula or the pulvinar nucleus.

SEEG-guided RF-thermocoagulation of epileptic foci: a therapeutic alternative for drug-resistant non-operable partial epilepsies.

BACKGROUND: Previous literature includes numerous reports of acute stereotactic ablation for epilepsy. Most reports focus on amygdalotomies or amygdalohippocampotomies, some others focus on various extra-limbic targets. These stereotactic techniques proved to have a less favourable outcome than that of standard surgery, so that their rather disappointing benefit/risk ratio explains why they have been largely abandoned. However, depth electrode recordings may be required in some cases of epilepsy surgery to delineate the best region of cortical resection. We usually implant depth electrodes according to Talairach's stereo electroencephalography (SEEG) methodology. Using these chronically implanted depth electrodes, we are able to perform radiofrequency (RF)-thermolesions of the epileptic foci. This paper reports the technical data required to perform such multiple cortical thermolesions, as well as the results in terms of seizure outcome in a group of 41 patients. TECHNICAL DATA: Lesions are placed in the cortex areas showing either a low amplitude fast pattern or spike-wave discharges at the onset of the seizures. Interictal paroxysmal activities are not considered for planning thermocoagulation sites. All targets are first functionally evaluated using electrical stimulation. Only those showing no clinical response to stimulation are selected for thermolesion, including sites located inside or near primary functional area. Lesions are performed using 120mA bipolar current (50 V), applied for 10-30 sec. Each thermocoagulation produces a 5-7mm diameter cortical lesion. A total of 2-31 lesions were performed in each of the 41 patients. Lesions are placed without anaesthesia. RESULTS: 20 patients (48.7%) experienced a seizure frequency decrease of at least 50% that was more than 80% in eight of them. One patient was seizure free after RF thermocoagulation. In 21 patients, no significant reduction of the seizure frequency was observed. Amongst the characteristics of the disease (age and sex of the patient, lobar localization of the EZ) and the characteristics of the thermocoagulations (topography, lateralization, number, morphology of the lesions on MRI) no factor was significantly linked to the outcome. However, the best results were clearly observed in epilepsies symptomatic of a cortical development malformation (CDM), with 67% of responders in this group of 20 patients (p = 0.052). Three transient post-procedure side-effects, consisting of paraesthetic sensations in the mouth (2 cases), and mild apraxia of the hand, were observed. CONCLUSION: SEEG-guided-RF-thermolesioning is a safe technique. Our results indicate that such lesions can lead to a significant reduction of seizure frequency. Our experience suggests that SEEG-guided RF thermocoagulation should be dedicated to drug-resistant epileptic patients for whom conventional resection surgery is risky or contra-indicated on the basis of invasive pre-surgical evaluation, particularly those suffering from epilepsy symptomatic of cortical development malformation.

Multiple sclerosis and epileptic seizures.

BACKGROUND: The association between epilepsy and multiple sclerosis (MS) is not a coincidence. OBJECTIVE: Our objective was to compare MS patients with or without history of seizures. METHODS: In a population of 5041 MS patients, we identified 102 (2%) patients with epileptic seizures. In 67 patients (1.3%), epileptic seizure could not be explained by any cause other than MS. RESULTS: In these 67 patients, the median age at occurrence of the first epileptic seizure was 33 years. Epilepsy was the initial clinical manifestation of MS in seven patients. In total, 62 patients (92.5%) presented only one or a few seizures, and 18 patients (27%) presented at least one episode of status epilepticus, fatal in two. Compared with MS patients without epilepsy, there was no difference in gender, type of MS course and time from onset of MS to the progressive phase. Conversely, the median age at MS onset was earlier (25.0 years vs. 30, p < 0.0001) and there was a trend for a shorter time from MS onset to non-reversible disability. CONCLUSIONS: Our study confirms an increased risk of epileptic seizures in MS patients. It underlines that seizures may be the first observable symptom in MS and the frequency and seriousness of status epilepticus.

Brainstem changes in 5-HT1A receptor availability during migraine attack.

BACKGROUND: Among serotonin receptors, 5-HT(1A) receptors are implicated in the regulation of central serotoninergic tone and could be involved in the abnormal brain 5-HT turnover suspected in migraineurs. The aim of this study was to investigate 5-HT(1A) receptors' availability during migraine attacks. METHODS: Ten patients suffering from odor-triggered migraine attacks and 10 control subjects were investigated using positron emission tomography (PET) and [(18)F]MPPF PET tracer, a selective 5-HT(1A) antagonist. All subjects underwent calibrated olfactory stimulations prior to the PET study. RESULTS: Four patients developed a migraine attack during the PET study. In these patients, statistical parametrical mapping and region of interest analyses showed an increased [(18)F]MPPF binding potential (BP(ND)) in the pontine raphe when compared to headache-free migraineurs and control subjects. This ictal change was confirmed at the individual level in each of the four affected patients. In comparison with the headache-free migraineurs, patients with a migraine attack also showed significantly increased [(18)F]MPPF BP(ND) in the left orbitofrontal cortex, precentral gyrus and temporal pole. No significant change in [(18)F]MPPF BP(ND) was observed between headache-free migraineurs and controls. CONCLUSIONS: Our results emphasize the role of 5HT(1A) receptors in the pontine raphe nuclei during the early stage of migraine attacks.

Stenting of a cerebral venous thrombosis.

Cerebral venous and sinus thrombosis (CVT) is a rare but potentially alarming condition, which remains a diagnostic and therapeutic challenge. Endovascular procedure may be a therapeutic option when evolution is unfavourable despite medical treatment, but the use of stenting is rarely reported in CVT treatment. We report the case of a man who presented a jugular vein thrombosis responsible for severe intracranial hypertension. Because of clinical worsening despite intravenous heparin and symptomatic treatment, endovascular procedure including the placement of five venous stents, thrombolysis and balloon angioplasty, was performed and led to venous recanalization with successful clinical outcome. The patient is still asymptomatic 3 years later. Our report shows that venous stenting could represent an efficient alternative in the management of decoagulation refractory CVT.

Somatotopic organization of pain responses to direct electrical stimulation of the human insular cortex.

The question whether pain encoding in the human insula shows some somatotopic organization is still pending. We studied 142 patients undergoing depth stereotactic EEG (SEEG) exploration of the insular cortex for pre-surgical evaluation of epilepsy. 472 insular electrical stimulations were delivered, of which only 49 (10.5%) elicited a painful sensation in 38 patients (27%). Most sites where low intensity electric stimulation produced pain, without after-discharge or concomitant visually detectable change in EEG activity outside the insula, were located in the posterior two thirds of the insula. Pain was located in a body area restricted to face, upper limb or lower limb for 27 stimulations (55%) and affected more than one of these regions for all others. The insular cortex being oriented parallel to the medial sagittal plane we found no significant difference between body segment representations in the medio-lateral axis. Conversely a somatotopic organization of sites where stimulation produced pain was observed along the rostro-caudal and vertical axis of the insula, showing a face representation rostral to those of upper and lower limbs, with an upper limb representation located above that of the lower limb. These data suggest that, in spite of large and often bilateral receptive fields, pain representation shows some degree of somatotopic organization in the human insula.

Reciprocal thalamocortical connectivity of the medial pulvinar: a depth stimulation and evoked potential study in human brain.

The thalamic medial pulvinar nucleus (PuM) is fully developed only in primates and reaches its greatest extent in humans. To assess the reciprocal functional connectivity between PuM and cortex, we studied intracerebral-evoked responses obtained after PuM and cortical electrical stimulation in 7 epileptic patients undergoing depth electroencephalographic recordings. Cortical-evoked potentials (CEPs) to PuM stimulation were recorded from all explored cortical regions, except striate cortex, anterior cingulated, and postcentral gyrus. Percentages of cortical contacts pairs responding to PuM stimulation (CEPs response rate) ranged from 80% in temporal neocortex, temporoparietal (TP) junction, insula, and frontoparietal opercular cortex to 34% in mesial temporal regions. Reciprocally, PuM-evoked potentials (PEPs) response rates were 14% after cortical stimulation in insula and frontoparietal opercular cortex, 67% in the TP junction, 76% in temporal neocortex, and 80% in mesial temporal regions. Overall, our study of functional PuM connectivity in the human brain converges with most of the data from anatomical studies in monkeys, except for a strong amygdalohippocampal functional projection to PuM and an unexpected imbalance between some of the reciprocal pathways explored. This functional quantitative approach helps to clarify the functional role of PuM as well as its implication in temporal lobe epileptic seizures.

SEEG-guided thermocoagulations: a palliative treatment of nonoperable partial epilepsies.

OBJECTIVE: Intracranial stereotactic EEG recordings (SEEG) in presurgical epilepsy assessment are currently carried out in our department. The SEEG method generally used for exploration can also be used to perform radiofrequency thermocoagulations (RFTC) of the epileptic foci. To assess the indications of the RFTC procedure in the therapeutic arsenal of drug-resistant epilepsies, we report the results obtained in 41 patients to whom RFTC was proposed as a first therapeutic step before surgery or as a palliative treatment when surgery was not possible. METHODS: RFTC were produced by applying a 50-volt, 110 mA current, during 10-30 seconds within the epileptogenic zone, as identified by the SEEG investigation. Two to 31 RFTC (mean, 12) were performed per patient. The median follow-up was 19 months (range: 4 to 72). RESULTS: Twenty patients (48.7%) experienced a seizure frequency decrease of at least 50%, which was over 80% in eight of them. One patient was seizure-free. The tolerance was excellent. A total of 67% of the 21 patients presenting a cortical development malformation benefited from RFTC (p = 0.052). In the group of noneligible patients for resective surgery (n = 13), six were responders to SEEG-guided RFTC and one of them was seizure-free. CONCLUSIONS: This study suggests that stereotactic EEG-guided radiofrequency thermocoagulations can be proposed only as a palliative procedure, able to bring a substantial improvement of seizure frequency, to drug-resistant patients with epilepsy for whom conventional resection surgery is risky or contraindicated on the basis of invasive presurgical evaluation.

Interictal brain 5-HT1A receptors binding in migraine without aura: a 18F-MPPF-PET study.

In this study we aimed to assess the brain distribution of 5-HT(1A) receptors in migraine patients without aura. Ten female migraine patients and 24 female healthy volunteers underwent magnetic resonance imaging and positron emission tomography using a radioligand antagonist of 5-HT(1A) receptors [4-(2'-methoxyphenyl)-1-[2'-(N-2-pirydynyl)-p-fluorobenzamido]-ethylpiperazine ((18)F-MPPF)]. A simplified reference tissue model was used to generate parametric images of 5-HT(1A) receptor binding potential (BP) values. Statistical Parametrical Mapping (SPM) analysis showed increased MPPF BP in posterior cortical areas and hippocampi bilaterally in patients compared with controls. Region of interest (ROI) analysis showed a non-significant trend in favour of a BP increase patients in cortical regions identified by the SPM analysis except in hippocampi, left parietal areas and raphe nuclei. During the interictal period of migraine patients without aura, the increase of MPPF BP in posterior cortical and limbic areas could reflect an increase in receptor density or a decrease of endogenous serotonin, which could explain their altered cortical excitability.