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Biomedical subjects

Philippe Kahane

Publications and source records attributed to Philippe Kahane.

At least 19 recordsLinked to original sources

Neural correlates of consolidation in working memory.

Many of our daily activities rely on a brain system called working memory, which implements our ability to encode information for short-term maintenance, possible manipulation, and retrieval. A recent intracranial study of patients performing a paradigmatic working memory task revealed that the maintenance of information involves a distributed network of oscillations in the gamma band (>40 Hz). Using a similar task, we focused on the encoding stage and targeted a process referred to as short-term consolidation, which corresponds to the encoding of novel items in working memory. The paradigm was designed to manipulate the subjects' intention to encode: series of 10 letters were presented, among which only five had to be remembered, as indicated by visual cues preceding or following each letter. During this task we recorded the intracerebral EEG of nine epileptic patients implanted in mesiotemporal structures, perisylvian regions, and prefrontal areas and used time-frequency analysis to search for neural activities simultaneous with the encoding of the letters into working memory. We found such activities in the form of increases of gamma band activity in a set of regions associated with the phonological loop, including the Broca area and the auditory cortex, and in the prefrontal cortex, the pre- and postcentral gyri, the hippocampus, and the fusiform gyrus.

Adult↗

Intracerebral dynamics of saccade generation in the human frontal eye field and supplementary eye field.

Recent functional imaging and electrical stimulation studies have localized in humans two frontal regions critical for the production of saccadic and anti-saccadic eye movements: the frontal and supplementary eye fields (FEF and SEF, respectively). We investigated the time course of their activations during the generation of pro- and anti-saccades from direct intracranial EEG recordings of three human epileptic patients. We found the preparation and the production of the saccades to be coincident with focal and transient increases of EEG power above 60 Hz. Those were produced in very specific brain sites distributed in the FEF and the SEF (as identified by previous human studies at a coarser time resolution). Furthermore, the spatio-temporal resolution of those recordings turned out to be sufficient to discriminate anatomically between several types of neural responses, determined either by the visual or by the motor components of the saccade tasks, and within this second category of responses, between some associated with the preparation of the saccades and others associated with their execution. Altogether, this study provides the first evidence of high-frequency neural responses in the generation of saccades in humans, and provides a firm basis for other studies detailing further the functional organization of the human oculomotor system at this level of spatial and temporal resolution.

Brain Mapping↗

Sudden unexpected death in epilepsy: from mechanisms to prevention.

PURPOSE OF REVIEW: To discuss the pathophysiology and potential prevention of sudden unexpected death in epilepsy. RECENT FINDINGS: Long-term electrocardiogram monitoring over several months has detected ictal asystole in three out of 20 (15%) patients with refractory epilepsy, suggesting that high-risk ictal arrhythmias occur in a greater proportion of patients with refractory epilepsy than previously thought. In case-control studies, sudden unexpected death in epilepsy was found to be associated with frequent generalized tonic-clonic seizures and greater ictal maximal heart rate, especially during nocturnal attacks. Conversely, supervision at night was associated with a lower risk of occurrence. The impact of epilepsy surgery on the risk of death and sudden unexpected death in epilepsy remains unclear, with comparable long-term survival in an epilepsy surgery cohort compared with a matched population of patients with refractory epilepsy who did not undergo surgery. Previous results may have been partly confounded by the association observed between preoperative decreased heart rate variability and poor postoperative seizure outcome. SUMMARY: Ictal arrhythmias may represent a more prevalent cause of sudden unexpected death in epilepsy than previously thought. No clear recommendations have emerged from the literature regarding the most appropriate therapeutic strategies to prevent the event, apart from the supervision at night of patients with refractory epilepsy.

Cause of Death↗

Relationship between intracerebral gamma oscillations and slow potentials in the human sensorimotor cortex.

Changes in sensorimotor rhythms (mu, beta and gamma) and movement-related cortical potentials (MRCPs) are both generated principally by the contralateral sensorimotor areas during the execution of self-paced movement. They appear to reflect movement control mechanisms, which remain partially unclear. With the aim of better understanding their sources and significance, we recorded MRCPs and sensorimotor rhythms during and after self-paced movement using intracerebral electrodes in eight epileptic subjects investigated by stereoelectroencephalography. The results showed that: (i) there is a strong spatial relationship between the late components of movement--the so-called motor potential (MP) and post-movement complex (PMc)--and gamma event-related synchronization (ERS) within the 40-60 Hz band, as the MP/PMc always occurred in contacts displaying gamma ERS (the primary sensorimotor areas), whereas mu and beta reactivities were more diffuse; and (ii) MPs and PMc are both generated by the primary motor and somatosensory areas, but with distinct sources. Hence, this could mean that kinesthesic sensory afferences project to neurons other than those firing during the pyramidal tract volley. The PMc and low gamma ERS represent two electrophysiological facets of kinesthesic feedback from the joints and muscles involved in the movement to the sensorimotor cortex. It could be suggested that gamma oscillations within the 40-60 Hz band could serve to synchronize the activities of the various neuronal populations involved in control of the ongoing movement.

Action Potentials↗

Nocturnal hypermotor seizures, suggesting frontal lobe epilepsy, can originate in the insula.

PURPOSE: To report three patients with drug-resistant nocturnal hypermotor seizures (NHSs), no detectable brain lesion, and clinically defined nocturnal frontal lobe epilepsy (NFLE) or autosomal dominant NLFE (ADNFLE), whose intracerebral EEG ictal onset primarily involved the insula, rather than the mesial or orbital frontal cortex. METHODS: Fourteen to 15 intracerebral electrodes were implanted in each patient, primarily sampling the frontal lobes with 80 to 91 recording leads covering the most likely side of seizure onset, and two to six leads placed within the ipsilateral insula. Electrical stimulation was used to test the epileptic threshold of frontal and insular brain regions at the various recording sites. RESULTS: In all three patients, a low-voltage fast activity was recorded within the anterosuperior aspect of the insula at ictal onset, either in isolation, or extending to the nearby frontal operculum in the ADNFLE patient. The role of the insula was further supported in all three patients either by the presence of high-amplitude spikes that clearly predominated over that region (n = 2) or by triggering the patient's typical aura or seizure when applying an electrical stimulation at that site, selectively (n = 2). CONCLUSIONS: The anterosuperior portion of the insula might play a pivotal role in generating nocturnal hypermotor seizures in some patients with nonlesional drug-resistant epilepsy suggesting NFLE or ADNFLE. Whether these patients are amenable to successful surgery remain an open issue.

Adolescent↗

The Bancaud and Talairach view on the epileptogenic zone: a working hypothesis.

The definition of the epileptogenic zone, as proposed by Talairach and Bancaud, is an ictal electro-clinical definition based on the results of stereotactic intracerebral EEG (SEEG) recordings. It takes into account not only the anatomical location of the "site of the beginning and of the primary organization" of the epileptic discharge, but also how this discharge gives rise to the accompanying clinical symptoms. This definition is different from the North American view since, for the French authors, the epileptogenic zone is not synonymous with what can be called the "what-to-remove area". In fact, it is above all a conceptual definition which emphazises the importance of studying the spatio-temporal dynamics of seizure discharges, and not only their starting point.

Cerebral Cortex↗

Towards a definition of the "practical" epileptogenic zone: a case of epilepsy with dual pathology.

Presurgical evaluation for patients with drug-resistant epilepsy requires the definition of various zones that have a variable spatial relationship with the epileptogenic zone. All the available methods to directly measure the actual seizure-onset zone and to define "the minimum amount of cortical tissue that must be resected to produce seizure-freedom" have significant limitations. We report on the case of a patient with dual pathology (hippocampal sclerosis and a post-traumatic scar) and discuss the contribution of the various presurgical investigations that led to surgery and seizure-freedom.

Adult↗

High gamma frequency oscillatory activity dissociates attention from intention in the human premotor cortex.

The premotor cortex is well known for its role in motor planning. In addition, recent studies have shown that it is also involved in nonmotor functions such as attention and memory, a notion derived from both animal neurophysiology and human functional imaging. The present study is an attempt to bridge the gap between these experimental techniques in the human brain, using a task initially designed to dissociate attention from intention in the monkey, and recently adapted for a functional magnetic resonance imaging (fMRI) study [Simon, S.R., Meunier, M., Piettre, L., Berardi, A.M., Segebarth, C.M., Boussaoud, D. (2002). Spatial attention and memory versus motor preparation: premotor cortex involvement as revealed by fMRI. J. Neurophysiol., 88, 2047-57]. Intracranial EEG was recorded from the cortical regions preferentially active in the spatial attention and/or working memory task and those involved in motor intention. The results show that, among the different intracranial EEG responses, only the high gamma frequency (60-200 Hz) oscillatory activity both dissociates attention/memory from motor intention and spatially colocalizes with the fMRI-identified premotor substrates of these two functions. This finding provides electrophysiological confirmation that the human premotor cortex is involved in spatial attention and/or working memory. Additionally, it provides timely support to the idea that high gamma frequency oscillations are involved in the cascade of neural processes underlying the hemodynamic responses measured with fMRI [Logothetis, N.K., Pauls, J., Augath, M., Trinath, T. and Oeltermann, A. (2001). Neurophysiological investigation of the basis of the fMRI signal. Nature, 412, 150-7], and suggests a functional selectivity of the gamma oscillations that could be critical for future EEG investigations, whether experimental or clinical.

Adult↗

The temporopolar cortex plays a pivotal role in temporal lobe seizures.

We investigated the role of the temporal pole (TP) in 48 consecutive patients with drug-refractory temporal lobe epilepsy (TLE). Chronic depth recordings of TP cortex activity were used in association with video recording of ictal symptoms during 48 spontaneous seizures. In 23 cases (48%, group 1) the TP was involved at the onset of the seizure, before or concurrently with the hippocampus. In the remaining 25 patients (52%, group 2) the TP was involved 16.4 +/- 13.8 s after the hippocampus. A past history of febrile seizures was found in both groups, with no statistical difference. Ictal symptoms did not differentiate TP seizures from seizures originating in the hippocampus but the first clinical sign occurred sooner in group 1 compared with group 2 (respectively 10.56 +/- 9 and 25.7 +/- 19 s, respectively, P = 0.005). Loss of awareness also occurred sooner in the case of TP seizures compared with mesiotemporal lobe (MTL) seizures (22.9 +/- 22.6 versus 42.2 +/- 18.6 s, P = 0.0002). MRI data analysis showed that hippocampal sclerosis was present in both groups of patients, although it was more frequent in patients with MTL onset. Anterior temporal white matter changes were found ipsilateral to the epileptogenic area and tended to be more frequent in patients with TP seizures. All the patients underwent tailored anterior temporal lobectomy that included the TP, the hippocampus, the parahippocampal gyrus and the anterior part of the lateral temporal cortex. A better postoperative outcome was achieved in group 1 compared with group 2 (Engel class 1, 95 and 72% respectively, P = 0.04). We conclude that the frequent TP involvement at the onset of seizures could be a supplementary explanation for some failures of selective amygdalohippocampectomy, which should be addressed preferentially to well-selected patients. Moreover, the involvement of the TP cortex at the onset of the seizures is a good predicting factor for postoperative seizure outcome.

Adolescent↗

The many faces of the gamma band response to complex visual stimuli.

While much is known about the functional architecture of the visual system, little is known about its large-scale dynamics during perception. This study describes this dynamics with a high spatial, temporal and spectral resolution. We recorded depth EEG of epileptic patients performing a face detection task and found that the stimuli induced strong modulations in the gamma band (40 Hz to 200 Hz) in selective occipital, parietal and temporal sites, in particular the fusiform gyrus, the lateral occipital gyrus and the intra-parietal sulcus. Occipito-temporal sites were the first to be activated, closely followed by the parietal sites, while portions of the primary visual cortex seemed to deactivate temporarily. Some of those effects were found to be correlated across distant sites, suggesting that a coordinated balance between regional gamma activations and deactivations could be involved during visual perception.

Adult↗

Intracerebral study of gamma rhythm reactivity in the sensorimotor cortex.

The generators and functional correlates of gamma oscillations within the sensorimotor cortex remain unclear. With the goal of locating the oscillations' sources precisely and then studying the relationship between oscillatory reactivity and ongoing movement, we recorded stereoelectroencephalograms with intracerebral electrodes in eight epileptic subjects awaiting surgical treatment. The sensorimotor cortex was free of lesions and was exhaustively explored with the electrodes. Subjects were asked to perform various self-paced movements contralateral to the exploration zone, brief and sustained, distal movements and a pointing movement. We used the event-related desynchronization method to quantify the reactivity of the 40-60-Hz band before, during and after the performance of movement. A very focused, event-related synchronization of gamma rhythms was found in all subjects. It was predominantly observed in the primary sensorimotor area and its distribution was consistent with the functional map established using electrical stimulations. Two different temporal patterns were observed, the event-related synchronization of gamma rhythms was related either to movement onset or to movement offset but was never recorded before movement. This observation suggests that gamma oscillations are more probably related to movement execution than to motor planning. The different patterns argue in favour of multiple functional roles; it has been shown that gamma oscillations may support the efferent drive to the muscles and here we show that they are also likely to be related to somatosensory integration. We therefore suggest that gamma oscillations in the 40-60-Hz band may support afferent sensory feedback to the sensorimotor cortex during the performance of movement.

Adolescent↗

The impact of epilepsy surgery on mortality.

Patients with refractory epilepsy suffer from an increased risk of death, primarily due to seizure-related fatalities including sudden unexpected death (SUDEP), which could be conceivably avoided by surgical cure of the epilepsy. Several series have addressed this issue by comparing the mortality rate between medically and surgically treated drug resistant populations, as well as between patients, seizure free and non seizure free post-operatively. Results from some studies suggest that successful temporal lobe surgery reduced the risk of death to that observed in the normal population, whereas patients who continue to suffer recurrent seizures still present an increased standardized mortality ratio (SMR). However, other series have failed to replicate this finding, or found no difference in the overall mortality and SUDEP rates between operated and medically treated patients. All the above studies suffer various types of methodological limitations, hampering any definite conclusion regarding the impact of epilepsy surgery on mortality. However, part of the apparently discordant reported findings might be reconciled through the following framework. Patients who will eventually respond favourably or unfavourably to an anterior temporal lobectomy might already differ in the risk of seizure-related death, pre-operatively. Specifically, patients whose temporal lobe epileptogenic network extends to the perisylvian region (temporal plus epilepsy) appear to be at higher risk of failed TLE surgery, secondary generalised tonic-clonic seizures, ictal apnoea or insula-driven severe cardiac arrhytmias. This population might carry most of the SUDEP burden, both pre- and post-operatively, accounting for the lack of an obvious net reduction of seizure related deaths after temporal lobe surgery. A multicentric study has recently been launched in order to test this hypothesis, and will hopefully help to conclude on the impact of epilepsy surgery on mortality outcome.

Cause of Death↗

Criticality and synchrony of fluctuations in rhythmical brain activity: pretransitional effects in epileptic patients.

In extending our previous results demonstrating critical fluctuations in electropathophysiological brain activity prior to onset of partial epileptic seizures, we used once again Haken's approach to self-organized complex systems, which resorts to identifying an order parameter. A renormalized density in phase space and a renormalized differential density were defined and substituted for the Lerner density, which we used previously. Fluctuations in electropathophysiological activity, consisting of periods of high activity recorded from both depth and scalp electrodes in six presurgical patients, were characterized on different time scales. Extension in space of the fluctuations was characterized by observing their synchronous occurrence in different areas of the brain. By simultaneously establishing the fluctuations' criticality, we were observing "synchronous instabilities". Criticality followed from characterizing the time course of the synchronously arising fluctuations, when approaching seizure onset (i). by their slowing, for the longer-lasting ones (up to about 2 min), and (ii). by their increase in rate of production, for those of shorter duration (up to 20-30 s). Critical behavior may be displayed in favorable cases over more than 1 h prior to seizure onset. Other effects are also described that in some cases may interfere with the simple time course of fluctuations and must be given further consideration, particularly with a view to application to seizure anticipation. Because periods of high activity are involved, any marker of increased electropathophysiological activity in the brain may, in principle, play the role of an order parameter or of an approximate order parameter, e.g., a signal's root-mean-square amplitude, or its excess energy content. Such markers may be put to use for the fluctuations they display or merely for their average time evolution prior to seizure onset. We compared the time evolution, prior to onset, of the excess production rate of synchronies and of the signals' excess energy content, both averaged over signal sections of a chosen duration. In view of potential noninvasive applications, those scalp electrodes showing effects similar to the observations we made at the epileptogenic focus were identified, and the time course of their order parameters prior to seizure onset was analyzed.

Brain↗

Late onset hyperekplexia.

We report on the case of an 86-year-old woman who rapidly became unable to stand and walk because of jerky movements, suggesting a clinical diagnosis of myoclonus. It was observed that both unexpected and expected stimuli (audiogenic, tactile, or visual) triggered the myoclonic jerks. Electrophysiological exploration, including a coupled EEG-EMG study, showed the occurrence of a patterned motor response to each stimulation (whatever the modality), consisting of eye blinking, head flexion, abduction of the upper arms, movement of the trunk, and bending of the knees. Given the absence of any relevant past history and lack of biological or neurological abnormalities including on CT scan brain imaging, the diagnosis of late-onset hyperekplexia was suggested. Substantial abatement of the clinical symptomatology was obtained after introduction of low-dose clonazepam.

Aged↗

Reappraisal of the human vestibular cortex by cortical electrical stimulation study.

The cortical areas with vestibular input in humans were assessed by electrical stimulation in 260 patients with partial epilepsy who had undergone stereotactic intracerebral electroencephalogram recordings before surgery. Vestibular symptoms were electrically induced on 44 anatomical sites in 28 patients. The patients experienced illusions of rotation (yaw plane: 18, pitch plane: 6, roll plane: 6), translations (n = 6), or indefinable feelings of body motion (n = 8). Almost all vestibular sites were located in the cortex (41/44): in the temporal (n = 19), parietal (n = 14), frontal (n = 5), occipital (n = 2), and insular (n = 1) lobes. Among these sites, we identified a lateral cortical temporoparietal area we called the temporo-peri-Sylvian vestibular cortex (TPSVC), from which vestibular symptoms, and above all rotatory sensations, were particularly easily elicited (24/41 cortical sites, 58.5%). This area extended above and below the Sylvian fissure, mainly inside Brodmann areas 40, 21, and 22. It included the parietal operculum (9/24 TPSVC sites) which was particularly sensitive for eliciting pitch plane illusions, and the mid and posterior part of the first and second temporal gyri (15/24 TPSVC sites) which preferentially caused yaw plane illusions. We suggest that the TPSVC could be homologous with the monkey's parietoinsular vestibular cortex.

Adolescent↗