Papers by Philippe Kahane

Annals of neurology, Jan 23, 2017
We aimed to 1) assess the concordance between various PMG types and the associated epileptogenic ... more We aimed to 1) assess the concordance between various PMG types and the associated epileptogenic zone (EZ), as defined by stereo-electroencephalography (SEEG), and 2) determine the postsurgical seizure outcome in PMG-related drug-resistant epilepsy. We retrospectively analyzed 58 cases: 49 had SEEG and 39 corticectomy or hemispherotomy. Mean age at SEEG or surgery was 28.3 years (range 2-50). PMG was bilateral in 9 (16%) patients and unilateral in 49, including 17 (29%) unilobar, 12 (21%) multilobar, 15 (26%) perisylvian, and only 5 (9%) hemispheric. Twenty-eight (48%) patients additionally had schizencephaly, heterotopia or focal cortical dysplasia. The SEEG-determined EZ was fully concordant with the PMG in only 8 (16%) cases, partially concordant in 74% and discordant in 10%. The EZ included remote cortical areas in 21 (43%) cases and was primarily localized in those in 5 (10%), all related to the mesial temporal structures. All but one PMG patients with corticectomy or hemispher...

Epilepsia, Nov 1, 2016
Many patients with medically refractory epilepsy now undergo successful surgery based on noninvas... more Many patients with medically refractory epilepsy now undergo successful surgery based on noninvasive diagnostic information, but intracranial electroencephalography (IEEG) continues to be used as increasingly complex cases are considered surgical candidates. The indications for IEEG and the modalities employed vary across epilepsy surgical centers; each modality has its advantages and limitations. IEEG can be performed in the same intraoperative setting, that is, intraoperative electrocorticography, or through an independent implantation procedure with chronic extraoperative recordings; the latter are not only resource intensive but also carry risk. A lack of understanding of IEEG limitations predisposes to data misinterpretation that can lead to denying surgery when indicated or, worse yet, incorrect resection with adverse outcomes. Given the lack of class 1 or 2 evidence on IEEG, a consensus-based expert recommendation on the diagnostic utility of IEEG is presented, with emphasis ...

Neurology, 2015
Objective: To identify the clinical determinants of occurrence of postictal generalized EEG suppr... more Objective: To identify the clinical determinants of occurrence of postictal generalized EEG suppression (PGES) after generalized convulsive seizures (GCS). Methods: We reviewed the video-EEG recordings of 417 patients included in the REPO 2 MSE study, a multicenter prospective cohort study of patients with drug-resistant focal epilepsy. According to ictal semiology, we classified GCS into 3 types: tonic-clonic GCS with bilateral and symmetric tonic arm extension (type 1), clonic GCS without tonic arm extension or flexion (type 2), and GCS with unilateral or asymmetric tonic arm extension or flexion (type 3). Association between PGES and person-specific or seizure-specific variables was analyzed after correction for individual effects and the varying number of seizures. Results: A total of 99 GCS in 69 patients were included. Occurrence of PGES was independently associated with GCS type (p , 0.001) and lack of early administration of oxygen (p , 0.001). Odds ratio (OR) for GCS type 1 in comparison with GCS type 2 was 66.0 (95% confidence interval [CI 5.4-801.6]). In GCS type 1, risk of PGES was significantly increased when the seizure occurred during sleep (OR 5.0, 95% CI 1.2-20.9) and when oxygen was not administered early (OR 13.4, 95% CI 3.2-55.9). Conclusion: The risk of PGES dramatically varied as a function of GCS semiologic characteristics. Whatever the type of GCS, occurrence of PGES was prevented by early administration of oxygen.
Epilepsia, 2014
There are at least five types of alterations of consciousness that occur during epileptic seizure... more There are at least five types of alterations of consciousness that occur during epileptic seizures: auras with illusions or hallucinations, dyscognitive seizures, epileptic delirium, dialeptic seizures, and epileptic coma. Each of these types of alterations of consciousness has a specific semiology and a distinct pathophysiologic mechanism. In this proposal we emphasize the need to clearly define each of these alterations/loss of consciousness and to apply this terminology in semiologic descriptions and classifications of epileptic seizures. The proposal is a consensus opinion of experienced epileptologists, and it is hoped that it will lead to systematic studies that will allow a scientific characterization of the different types of alterations/loss of consciousness described in this article.

Annals of neurology, Jan 23, 2017
We aimed to 1) assess the concordance between various PMG types and the associated epileptogenic ... more We aimed to 1) assess the concordance between various PMG types and the associated epileptogenic zone (EZ), as defined by stereo-electroencephalography (SEEG), and 2) determine the postsurgical seizure outcome in PMG-related drug-resistant epilepsy. We retrospectively analyzed 58 cases: 49 had SEEG and 39 corticectomy or hemispherotomy. Mean age at SEEG or surgery was 28.3 years (range 2-50). PMG was bilateral in 9 (16%) patients and unilateral in 49, including 17 (29%) unilobar, 12 (21%) multilobar, 15 (26%) perisylvian, and only 5 (9%) hemispheric. Twenty-eight (48%) patients additionally had schizencephaly, heterotopia or focal cortical dysplasia. The SEEG-determined EZ was fully concordant with the PMG in only 8 (16%) cases, partially concordant in 74% and discordant in 10%. The EZ included remote cortical areas in 21 (43%) cases and was primarily localized in those in 5 (10%), all related to the mesial temporal structures. All but one PMG patients with corticectomy or hemispher...

Epilepsia, Nov 1, 2016
Many patients with medically refractory epilepsy now undergo successful surgery based on noninvas... more Many patients with medically refractory epilepsy now undergo successful surgery based on noninvasive diagnostic information, but intracranial electroencephalography (IEEG) continues to be used as increasingly complex cases are considered surgical candidates. The indications for IEEG and the modalities employed vary across epilepsy surgical centers; each modality has its advantages and limitations. IEEG can be performed in the same intraoperative setting, that is, intraoperative electrocorticography, or through an independent implantation procedure with chronic extraoperative recordings; the latter are not only resource intensive but also carry risk. A lack of understanding of IEEG limitations predisposes to data misinterpretation that can lead to denying surgery when indicated or, worse yet, incorrect resection with adverse outcomes. Given the lack of class 1 or 2 evidence on IEEG, a consensus-based expert recommendation on the diagnostic utility of IEEG is presented, with emphasis ...

Neurology, 2015
Objective: To identify the clinical determinants of occurrence of postictal generalized EEG suppr... more Objective: To identify the clinical determinants of occurrence of postictal generalized EEG suppression (PGES) after generalized convulsive seizures (GCS). Methods: We reviewed the video-EEG recordings of 417 patients included in the REPO 2 MSE study, a multicenter prospective cohort study of patients with drug-resistant focal epilepsy. According to ictal semiology, we classified GCS into 3 types: tonic-clonic GCS with bilateral and symmetric tonic arm extension (type 1), clonic GCS without tonic arm extension or flexion (type 2), and GCS with unilateral or asymmetric tonic arm extension or flexion (type 3). Association between PGES and person-specific or seizure-specific variables was analyzed after correction for individual effects and the varying number of seizures. Results: A total of 99 GCS in 69 patients were included. Occurrence of PGES was independently associated with GCS type (p , 0.001) and lack of early administration of oxygen (p , 0.001). Odds ratio (OR) for GCS type 1 in comparison with GCS type 2 was 66.0 (95% confidence interval [CI 5.4-801.6]). In GCS type 1, risk of PGES was significantly increased when the seizure occurred during sleep (OR 5.0, 95% CI 1.2-20.9) and when oxygen was not administered early (OR 13.4, 95% CI 3.2-55.9). Conclusion: The risk of PGES dramatically varied as a function of GCS semiologic characteristics. Whatever the type of GCS, occurrence of PGES was prevented by early administration of oxygen.

Epileptic disorders : international epilepsy journal with videotape, 2014
A high rate of abnormal social behavioural traits or perceptual deficits is observed in children ... more A high rate of abnormal social behavioural traits or perceptual deficits is observed in children with unilateral temporal lobe epilepsy. In the present study, perception of auditory and visual social signals, carried by faces and voices, was evaluated in children or adolescents with temporal lobe epilepsy. We prospectively investigated a sample of 62 children with focal non-idiopathic epilepsy early in the course of the disorder. The present analysis included 39 children with a confirmed diagnosis of temporal lobe epilepsy. Control participants (72), distributed across 10 age groups, served as a control group. Our socio-perceptual evaluation protocol comprised three socio-visual tasks (face identity, facial emotion and gaze direction recognition), two socio-auditory tasks (voice identity and emotional prosody recognition), and three control tasks (lip reading, geometrical pattern and linguistic intonation recognition). All 39 patients also benefited from a neuropsychological examina...
Epilepsy & Behavior, 2013
Epilepsia, 2010
Purpose: Focal cortical dysplasias (FCD) are localized regions of malformed cerebral cortex and a... more Purpose: Focal cortical dysplasias (FCD) are localized regions of malformed cerebral cortex and are very frequently associated with epilepsy in both children and adults. A broad spectrum of histopathology has been included in the diagnosis of FCD. An ILAE task force proposes an international consensus classification system to better characterize specific clinicopathological FCD entities. 1 All authors were members of the ILAE Task Force of the Diagnostic Methods Commission, with the exception of DDA and FC. 2 Chair of the ILAE Task Force.

Epilepsia, 2013
Cerebral cavernous malformations (CCMs) are well-defined, mostly singular lesions present in 0.4-... more Cerebral cavernous malformations (CCMs) are well-defined, mostly singular lesions present in 0.4-0.9% of the population. Epileptic seizures are the most frequent symptom in patients with CCMs and have a great impact on social function and quality of life. However, patients with CCM-related epilepsy (CRE) who undergo surgical resection achieve postoperative seizure freedom in only about 75% of cases. This is frequently because insufficient efforts are made to adequately define and resect the epileptogenic zone. The Surgical Task Force of the Commission on Therapeutics of the International League Against Epilepsy (ILAE) and invited experts reviewed the pertinent literature on CRE. Definitions of definitive and probable CRE are suggested, and recommendations regarding the diagnostic evaluation and etiology-specific management of patients with CRE are made. Prospective trials are needed to determine when and how surgery should be done and to define the relations of the hemosiderin rim to the epileptogenic zone.

Brain Sciences, 2021
Direct cortical stimulation (DCS) in epilepsy surgery patients has a long history of functional b... more Direct cortical stimulation (DCS) in epilepsy surgery patients has a long history of functional brain mapping and seizure triggering. Here, we review its findings when applied to the insula in order to map the insular functions, evaluate its local and distant connections, and trigger seizures. Clinical responses to insular DCS are frequent and diverse, showing a partial segregation with spatial overlap, including a posterior somatosensory, auditory, and vestibular part, a central olfactory-gustatory region, and an anterior visceral and cognitive-emotional portion. The study of cortico-cortical evoked potentials (CCEPs) has shown that the anterior (resp. posterior) insula has a higher connectivity rate with itself than with the posterior (resp. anterior) insula, and that both the anterior and posterior insula are closely connected, notably between the homologous insular subdivisions. All insular gyri show extensive and complex ipsilateral and contralateral extra-insular connections, ...

Cortex; a journal devoted to the study of the nervous system and behavior, Sep 23, 2017
Ripples are high-frequency bouts of coordinated hippocampal activity believed to be crucial for i... more Ripples are high-frequency bouts of coordinated hippocampal activity believed to be crucial for information transfer and memory formation. We used intracortical macroelectrodes to record neural activity in the human hippocampus of awake subjects undergoing surgical treatment for refractory epilepsy and distinguished two populations of ripple episodes based on their frequency spectrum. The phase-coupling of one population, slow ripples (90-110 Hz), to cortical delta oscillations was differentially modulated by cognitive task; whereas the second population, fast ripples (130-170 Hz), was not seemingly correlated to local neural activity. Furthermore, as cognitive tasks changed, the ongoing coordination of neural activity associated to slow ripples progressively augmented along the parahippocampal axis. Thus, during resting states, slow ripples were coordinated in restricted hippocampal territories; whereas during active states, such as attentionally-demanding tasks, high frequency act...

Epilepsia, Dec 1, 2016
Interictal [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) is used in the presurgi... more Interictal [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) is used in the presurgical evaluation of patients with drug-resistant focal epilepsy. We aimed at clarifying its relationships with ictal high-frequency oscillations (iHFOs) shown to be a relevant marker of the seizure-onset zone. We studied the correlation between FDG-PET and epileptogenicity maps in an unselected series of 37 successive patients having been explored with stereo-electroencephalography (SEEG). At the group level, we found a significant correlation between iHFOs and FDG-PET interictal hypometabolism only in cases of temporal lobe epilepsy. This correlation was found with HFOs, and the same comparison between FDG-PET and ictal SEEG power of lower frequencies during the same epochs did not show the same significance. This finding suggests that interictal FDG-PET and ictal HFOs may share common underlying pathophysiologic mechanisms of ictogenesis in temporal lobe epilepsy, and combining both feat...

NeuroImage, 2017
Goal-directed motor behavior is associated with changes in patterns of rhythmic neuronal activity... more Goal-directed motor behavior is associated with changes in patterns of rhythmic neuronal activity across widely distributed brain areas. In particular, movement initiation and execution are mediated by patterns of synchronization and desynchronization that occur concurrently across distinct frequency bands and across multiple motor cortical areas. To date, motor-related local oscillatory modulations have been predominantly examined by quantifying increases or suppressions in spectral power. However, beyond signal power, spectral properties such as phase and phase-amplitude coupling (PAC) have also been shown to carry information with regards to the oscillatory dynamics underlying motor processes. Yet, the distinct functional roles of phase, amplitude and PAC across the planning and execution of goal-directed motor behavior remain largely elusive. Here, we address this question with unprecedented resolution thanks to multi-site intracerebral EEG recordings in human subjects while they performed a delayed motor task. To compare the roles of phase, amplitude and PAC, we monitored intracranial brain signals from 748 sites across six medically intractable epilepsy patients at movement execution, and during the delay period where motor intention is present but execution is withheld. In particular, we used a machine-learning framework to identify the key contributions of various neuronal responses. We found a high degree of overlap between brain network patterns observed during planning and those present during execution. Prominent amplitude increases in the delta (2-4 Hz) and high gamma (60-200 Hz) bands were observed during both planning and execution. In contrast, motor alpha (8-13 Hz) and beta (13-30 Hz) power were suppressed during execution, but enhanced during the delay period. Interestingly, single-trial classification revealed that low-frequency phase information, rather than spectral power change, was the most discriminant feature in dissociating action from intention. Additionally, despite providing weaker decoding, PAC features led to statistically significant classification of motor states, particularly in anterior cingulate cortex and premotor brain areas. These results advance our understanding of the distinct and partly overlapping involvement of phase, amplitude and the coupling between them, in the neuronal mechanisms underlying motor intentions and executions.

Cerebral Cortex, 2016
The ability to monitor our own errors is mediated by a network that includes dorsomedial prefront... more The ability to monitor our own errors is mediated by a network that includes dorsomedial prefrontal cortex (dmPFC) and anterior insula (AI). However, the dynamics of the underlying neurophysiological processes remain unclear. In particular, whether AI is on the receiving or driving end of the error-monitoring network is unresolved. Here, we recorded intracerebral electroencephalography signals simultaneously from AI and dmPFC in epileptic patients while they performed a stop-signal task. We found that errors selectively modulated broadband neural activity in human AI. Granger causality estimates revealed that errors were immediately followed by a feedforward influence from AI onto anterior cingulate cortex and, subsequently, onto presupplementary motor area. The reverse pattern of information flow was observed on correct responses. Our findings provide the first direct electrophysiological evidence indicating that the anterior insula rapidly detects and conveys error signals to dmPFC, while the latter might use this input to adapt behavior following inappropriate actions.

Cortex; a journal devoted to the study of the nervous system and behavior, 2014
Face processing depends on the orchestrated activity of a large-scale neuronal network. Its activ... more Face processing depends on the orchestrated activity of a large-scale neuronal network. Its activity can be modulated by attention as a function of task demands. However, it remains largely unknown whether voluntary, endogenous attention and reflexive, exogenous attention to facial expressions equally affect all regions of the face-processing network, and whether such effects primarily modify the strength of the neuronal response, the latency, the duration, or the spectral characteristics. We exploited the good temporal and spatial resolution of intracranial electroencephalography (iEEG) and recorded from depth electrodes to uncover the fast dynamics of emotional face processing. We investigated frequency-specific responses and event-related potentials (ERP) in the ventral occipito-temporal cortex (VOTC), ventral temporal cortex (VTC), anterior insula, orbitofrontal cortex (OFC), and amygdala when facial expressions were task-relevant or task-irrelevant. All investigated regions of ...

Frontiers in Psychology, 2015
If conscious perception requires global information integration across active distant brain netwo... more If conscious perception requires global information integration across active distant brain networks, how does the loss of conscious perception affect neural processing in these distant networks? Pioneering studies on perceptual suppression (PS) described specific local neural network responses in primary visual cortex, thalamus and lateral prefrontal cortex of the macaque brain. Yet the neural effects of PS have rarely been studied with intracerebral recordings outside these cortices and simultaneously across distant brain areas. Here, we combined (1) a novel experimental paradigm in which we produced a similar perceptual disappearance and also reappearance by using visual adaptation with transient contrast changes, with (2) electrophysiological observations from human intracranial electrodes sampling wide brain areas. We focused on broadband high-frequency (50-150 Hz, i.e., gamma) and low-frequency (8-24 Hz) neural activity amplitude modulations related to target visibility and invisibility. We report that low-frequency amplitude modulations reflected stimulus visibility in a larger ensemble of recording sites as compared to broadband gamma responses, across distinct brain regions including occipital, temporal and frontal cortices. Moreover, the dynamics of the broadband gamma response distinguished stimulus visibility from stimulus invisibility earlier in anterior insula and inferior frontal gyrus than in temporal regions, suggesting a possible role of fronto-insular cortices in top-down processing for conscious perception. Finally, we report that in primary visual cortex only low-frequency amplitude modulations correlated directly with perceptual status. Interestingly, in this sensory area broadband gamma was not modulated during PS but became positively modulated after 300 ms when stimuli were rendered visible again, suggesting that local networks could be ignited by top-down influences during conscious perception.

Frontiers in human neuroscience, 2011
After intensive practice, unfamiliar letter strings become familiar words and reading speed incre... more After intensive practice, unfamiliar letter strings become familiar words and reading speed increases strikingly from a slow processing to a fast and with more global recognition of words. While this effect has been well documented at the behavioral level, its neural underpinnings are still unclear. The question is how the brain modulates the activity of the reading network according to the novelty of the items. Several models have proposed that familiar and unfamiliar words are not processed by separate networks but rather by common regions operating differently according to familiarity. This hypothesis has proved difficult to test at the neural level because the effects of familiarity and length on reading occur (a) on a millisecond scale, shorter than the resolution of fMRI and (b) in regions which cannot be isolated with non-invasive EEG or MEG. We overcame these limitations by using invasive intra-cerebral EEG recording in epileptic patients. Neural activity (gamma-band respons...
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Papers by Philippe Kahane