A machine learning approach to explore cognitive signatures in patients with temporo-mesial epilepsy.

We aimed to identify cognitive signatures (phenotypes) of patients suffering from mesial temporal lobe epilepsy (mTLE) with respect to their epilepsy lateralization (left or right), through the use of SVM (Support Vector Machine) and XGBoost (eXtreme Gradient Boosting) machine learning (ML) algorithms. Specifically, we explored the ability of the two algorithms to identify the most significant scores (features, in ML terms) that segregate the left from the right mTLE patients. We had two versions of our dataset which consisted of neuropsychological test scores: a "reduced and working" version (n = 46 patients) without any missing data, and another one "original" (n = 57) with missing data but useful for testing the robustness of results obtained with the working dataset. The emphasis was placed on a precautionary machine learning (ML) approach for classification, with reproducible and generalizable results. The effects of several clinical medical variables were also studied. We obtained excellent predictive classification performances (>75%) of left and right mTLE with both versions of the dataset. The most segregating features were four language and memory tests, with a remarkable stability close to 100%. Thus, these cognitive tests appear to be highly relevant for neuropsychological assessment of patients. Moreover, clinical variables such as structural asymmetry between hippocampal gyri, the age of patients and the number of anti-epileptic drugs, influenced the cognitive phenotype. This exploratory study represents an in-depth analysis of cognitive scores and allows observing interesting interactions between language and memory performance. We discuss implications of these findings in terms of clinical and theoretical applications and perspectives in the field of neuropsychology.

A real-time marker of object-based attention in the human brain. A possible component of a "gate-keeping mechanism" performing late attentional selection in the Ventro-Lateral Prefrontal Cortex.

The decision to process an incoming stimulus attentively - and to trigger a follow-up cascade of high-level processes - is strategic for the human brain as it becomes transiently unavailable to subsequent stimulus processing. In this study, we set to identify brain networks that carry out such evaluations. We therefore assessed the time-course of neural responses with intracerebral EEG in human patients during an attentional reading task, contrasting to-be-attended vs. to-be-ignored items. We measured High-Frequency Activity [50-150 â€‹Hz] as a proxy of population-level spiking activity and we identified a crucial component of a Gate-Keeping Mechanism bilateral in the mid-Ventro-Lateral Prefrontal Cortex (VLPFC), at the interplay of the Ventral and Dorsal Attention Networks, that selectively reacts before domain specialized cortical regions that engage in full stimulus analysis according to task demands.

The concept of temporal 'plus' epilepsy.

The concept of temporal 'plus' epilepsy (T+E) is not new, and a number of observations made by means of intracerebral electrodes have illustrated the complexity of neuronal circuits that involve the temporal lobe. The term T+E was used to unify and better individualize these specific forms of multilobar epilepsies, which are characterized by electroclinical features primarily suggestive of temporal lobe epilepsy, MRI findings that are either unremarkable or show signs of hippocampal sclerosis, and intracranial recordings which demonstrate that seizures arise from a complex epileptogenic network including a combination of brain regions located within the temporal lobe and over closed neighbouring structures such as the orbitofrontal cortex, the insulo-opercular region, and the temporo-parieto-occipital junction. We will review here how the term of T+E has emerged, what it means, and which practical consideration it raises.

Rehabilitation of verbal memory by means of preserved nonverbal memory abilities after epilepsy surgery.

We present a patient with epilepsy who underwent left anterior temporal cortex resection, sparing the hippocampus, to stop drug-refractory seizures. Given that one year after surgery the patient showed verbal memory difficulties, we proposed a short (twelve weeks) and intensive (two times a week) training based on visual imagery strategies as the nonverbal memory abilities were preserved. Neuropsychological and fMRI assessments were performed before and after rehabilitation to evaluate the cognitive progress and cerebral modifications induced by this rehabilitation program. Our results showed that the rehabilitation program improved both scores for verbal memory and the everyday quality of life. Changes in cerebral activity highlighted by fMRI suggest that the program might have facilitated the development of compensatory strategies, as reflected by the shift of activation from the anterior to the posterior cerebral network during a verbal memory task. One year after the rehabilitation program, the patient reported using mental imagery in everyday life for routine and professional activities. Although supplementary evidence is necessary to increase the robustness of these findings, this case report suggests that an efficient rehabilitation program is feasible and (a) should be based on the individual cognitive profile and on the preserved cognitive abilities, (b) can be short but intensive, (c) can be applied even months after the lesion occurrence, and (d) can induce a positive effect which may be sustainable over time.

Turning visual shapes into sounds: early stages of reading acquisition revealed in the ventral occipitotemporal cortex.

The exact role of the left ventral occipitotemporal cortex (VOTC) during the initial stages of reading acquisition is a hotly debated issue, especially regarding the comparative effect of learning on early stimulus-dependent vs. later task-dependent processes. We show that this controversy can be solved with high-temporal resolution intracerebral EEG recordings of the VOTC. We measured High-Frequency Activity (50-150 Hz) as a proxy of population-level spiking activity while participants learned Japanese Katakana symbols, and found that learning primarily affects top-down/task-dependent neural processing, after a few minutes only. In contrast, adaptation of early bottom-up/stimulus-dependent processing takes several days to adapt and provides the basis for fluent reading. Such evidence that two consecutive stages of neural processing, stimulus- and task-dependent are differentially affected by learning, can reconcile seemingly opposite hypotheses on the role of the VOTC during reading acquisition.

Directed differential connectivity graph of interictal epileptiform discharges.

In this paper, we study temporal couplings between interictal events of spatially remote regions in order to localize the leading epileptic regions from intracerebral EEG (iEEG). We aim to assess whether quantitative epileptic graph analysis during interictal period may be helpful to predict the seizure onset zone of ictal iEEG. Using wavelet transform, cross-correlation coefficient, and multiple hypothesis test, we propose a differential connectivity graph (DCG) to represent the connections that change significantly between epileptic and nonepileptic states as defined by the interictal events. Postprocessings based on mutual information and multiobjective optimization are proposed to localize the leading epileptic regions through DCG. The suggested approach is applied on iEEG recordings of five patients suffering from focal epilepsy. Quantitative comparisons of the proposed epileptic regions within ictal onset zones detected by visual inspection and using electrically stimulated seizures, reveal good performance of the present method.

Comparison of five directed graph measures for identification of leading interictal epileptic regions.

Directed graphs (digraphs) derived from interictal periods of intracerebral EEG (iEEG) recordings can be used to estimate the leading interictal epileptic regions for presurgery evaluations. For this purpose, quantification of the emittance contribution of each node to the rest of digraph is important. However, the usual digraph measures are not very well suited for this quantification. Here, we compare the efficiency of recently introduced local information (LI) measure and a new measure called total global efficiency with classical measures like global efficiency, local efficiency and node degree. For evaluation, the estimated leading interictal epileptic regions based on five measures are compared with seizure onset zones obtained by visual inspection of epileptologists for five patients. The comparison revealed the superior performance of the LI measure. We showed efficiency of different digraph measures for the purpose of source and sink node identification.

[Basal ganglia deep-brain stimulation for treatment of drug-resistant epilepsy: review and current data]. / La stimulation cérébrale profonde des ganglions de la base comme traitement des épilepsies pharmacorésistantes: revue et données actuelles.

The surgical treatment of intractable epilepsies involving eloquent areas of the cortex is still challenging. Deep-brain stimulation could be an alternative to resective surgery because it can modulate the remote control systems of epilepsy, such as the thalamus and basal ganglia. The surgical experience acquired in the field of movement disorder surgery and the low morbidity of this technic could allow one to apply DBS to intractable epilepsies, such as generalized, motor and bitemporal epilepsies. Here we discuss the main experimental and clinical data reported so far in the literature and taken from our own experience.

[Epileptic seizure and migraine visual aura: revisiting migralepsy]. / Aura visuelle migraineuse et crise épileptique: la migralepsie revisitée.

INTRODUCTION: The term of "migralepsy" has been proposed to define migraine-triggered epileptic seizures. Although already reported in the literature for more than fifty years, a number of observations remain debatable because of possible confusion between migraine and epileptic seizure clinical manifestations, including hemifield visual hallucinations, digestive signs and severe headache. OBSERVATION: We report on the case of a young patient suffering from both diseases, in whom a visual aura preceded either migraine attacks or epileptic generalized tonic-clonic seizure. Subtle modification in the primitive visual hallucination, which suddenly contained colored figures and was accompanied by fear before a prolonged loss of contact, suggested a continuum between migraine aura and epileptic seizure in this patient. Brain MRI was normal and EEG showed some sharp waves in the right posterior area. CONCLUSION: The presence of a neurophysiological continuum between migrainous aura and epileptic seizure is supported by this observation of "migralepsy". Recent findings from genetic and epidemiological studies further support this link.

[Temporal disconnection as an alternative treatment for intractable temporal lobe epilepsy: techniques, complications and results]. / Déconnexion du lobe temporal dans les épilepsies temporales pharmacorésistantes: techniques, complications et résultats.

Temporal lobe epilepsy (TLE) is the most common form of intractable partial epilepsy in adults. Surgery (lobectomy or amygdalohippocampectomy) is effective in most patients. However, some complications can occur and brain shift, hematoma into the post operative cavity and occulomotor nerve palsy have been reported due to the surgical technic. We report the technique, safety and efficacy of temporal disconnection in nonlesional TLE. Forty-seven patients (18 males, 29 females; handedness: 12 left, 33 right; aged 35 years+/-10; mean duration of epilepsy: 24+/-10 years) underwent temporal disconnection (20 left, 27 right) guided by neuronavigation. Sixteen patients (35 %) underwent additional presurgical evaluation with SEEG. The outcome was assessed using Engel's classification. At the two-year follow-up, 85 % of the patients were seizure-free (Engel I), 26 (58 %) of whom were Ia. Postoperative persistent morbidity included mild hemiparesis (n=1), mild facial paresis (n=1), quadranopsia (n=23) and hemianopia (n=1). Verbal memory worsened in 13 % of cases when the disconnection was performed in the dominant lobe. MRI follow-up showed two cases of nonsymptomatic thalamic or pallidal limited ischemias, two cases of temporal horn-cystic dilatation, one requiring surgical reintervention without sequelae. There was one case of postoperative phlebitis. In the seizure-free patient group, postoperative EEG showed interictal temporal spikes at three months, one year and two years located in the anterior temporal region. Temporal disconnection is effective, prevents the occurrence of subdural cyst and hematomas in the temporal cavity, prevents the occurrence of oculomotor palsy, and limits the occurrence of quadranopsia. However, comparative studies are required to evaluate temporal disconnection as an alternative to lobectomy in nonlesional TLE.

Brain mapping of digestive sensations elicited by cortical electrical stimulations.

The aim of the study was to obtain a comprehensive map of cortical areas from where digestive sensations during intracerebral electrical stimulations (ES) in epileptic patients are elicited. Direct cortical ESs were performed in 339 medically intractable epileptic patients selected to presurgical evaluation using chronically stereotaxically implanted intracerebral electrodes and audio-video-EEG monitoring system. Digestive sensations were electrically induced on 723 different anatomical sites in 172 subjects (51%). According to the exclusion criteria, the final analysis includes 174 relevant stimulations evoked in 87 patients. The reported sensations referred predominantly to the upper part of the digestive tract including the epigastria and area over the periumbilical (n = 83; 48%), retrosternal (n = 17; 10%), pharyngeal (n = 31; 18%) and oral (n = 18; 10%) regions. The temporal pole (BA 38), hippocampus, amygdala and anterior cingulate cortex (ACC; BA 24/BA 32) were the typical anatomical locations connected with epigastric sensations. Retrosternal sensations were preferentially related to the ACC, while oro-pharyngeal sensations were most related to the suprasylvian opercular cortex and the insula. Cortical ESs are followed by a great variability of induced digestive and associated symptoms corresponding to a widely distributed cortical network of visceral sensation processing, in which the limbic and paralimbic structures play a critical role.

Silence is golden: transient neural deactivation in the prefrontal cortex during attentive reading.

It is becoming increasingly clear that attention-demanding tasks engage not only activation of specific cortical regions but also deactivation of other regions that could interfere with the task at hand. At the same time, electrophysiological studies in animals and humans have found that the participation of cortical regions to cognitive processes translates into local synchronization of rhythmic neural activity at frequencies above 40 Hz (so-called gamma-band synchronization). Such synchronization is seen as a potential facilitator of neural communication and synaptic plasticity. We found evidence that cognitive processes can also involve the disruption of gamma-band activity in high-order brain regions. Intracerebral electroencephalograms were recorded in 3 epileptic patients during 2 reading tasks. Visual presentation of words induced a strong deactivation in a broad (20-150 Hz) frequency range in the left ventral lateral prefrontal cortex, in parallel with gamma-band activations within the reading network, including Broca's area. The observed energy decrease in neural signals was reproducible across patients. It peaked around 500 ms after stimulus onset and appeared subject to attention-modulated amplification. Our results suggest that cognition might be mediated by a coordinated interaction between regional gamma-band synchronizations and desynchronizations, possibly reflecting enhanced versus reduced local neural communication.

Ictal clinical and scalp-EEG findings differentiating temporal lobe epilepsies from temporal 'plus' epilepsies.

Temporal 'plus' epilepsies are characterized by seizures involving a complex epileptogenic network including the temporal lobe and the closed neighboured structures such as the orbito-frontal cortex, the insula, the frontal and parietal operculum and the temporo-parieto-occipital junction. Temporal 'plus' epilepsies are currently identified by means of intracerebral electrodes but whether their diagnosis can be suspected non-invasively has not been evaluated yet. The aim of this retrospective study was to address this issue in 80 consecutive patients who were thought to suffer from non-lesional temporal lobe seizures which finally proved, on the basis of stereotactic intracerebral EEG (SEEG) recordings, to be 'purely' temporal (TL group, n = 58) or temporal 'plus' (T+ group, n = 22). Our results showed that the two groups of patients were difficult to differentiate on the basis of general clinical features or MRI data. Even the presence of hippocampal sclerosis did not distinguish the two groups. Conversely, both ictal clinical symptoms and scalp-EEG findings significantly differentiated TL from T+ patients. Patients with TL epilepsies more frequently presented an ability to warn at seizure onset (P = 0.003), an abdominal aura (P = 0.05), gestural automatisms (P = 0.04) and a post-ictal amnesia (P = 0.02). Patients suffering from T+ epilepsies more frequently had gustatory hallucinations (P = 0.02), rotatory vertigo (P = 0.02) and auditory illusions (P = 0.02) at seizure onset; they exhibited more frequently contraversive manifestations of the eyes and/or head (P = 0.001), piloerection (P = 0.03) and ipsilateral tonic motor signs (P = 0.05), and they were more often dysphoric in the post-ictal phase (P = 0.0001). Cluster analysis mainly indicated that some associations of symptoms were relevant for differentiating TL cases from T+ cases. Interictal EEG of T+ patients more frequently exhibited bilateral or precentral abnormalities, while ictal EEG more frequently pointed over the anterior frontal, temporo-parietal and precentral regions. Neither TL interictal spikes, nor TL ictal EEG onset, allowed us definitely to rule out the possibility of T+ epilepsies. Our findings may be useful for identifying, among patients suffering from 'atypical' non-lesional TL epilepsies, those who should undergo invasive recordings before surgery.

Intracerebral recordings of nocturnal hyperkinetic seizures: demonstration of a longer duration of the pre-seizure sleep spindle.

OBJECTIVE: Nocturnal frontal lobe epilepsy (NFLE) seizures occur primarily during non-rapid eye movement sleep stage 2. We observed in several patients rhythms of same localization and frequency as sleep spindles, immediately preceding and sometimes continuing at seizure onsets. We aimed to study the link between sleep spindles and seizure onsets. METHODS: We used intracerebral stereo-EEG ictal recordings of two MRI-negative patients with clinically defined NFLE. For each of the six studied seizures, sustained activity in the frontal sleep spindle frequency (12Hz) was observed around seizure onset. The duration of this pre-seizure sleep spindle was compared to that of the 10 preceding sleep spindles. RESULTS: The pre-seizure sleep spindles were clearly of longer duration than the "interictal" sleep spindles for all seizures. This sustained pre-seizure 12Hz activity could be differentiated from normal awakenings, and showed no spatial relation to the ictal onset. CONCLUSIONS: We demonstrated a functional alteration of the sleep spindle-generating thalamocortical loop concomitant with the seizure onsets. This defect may also be involved in seizure generation. SIGNIFICANCE: A thalamic participation in NFLE pathogenesis is likely in our two patients. The study of additional patients will allow to evaluate the role of the thalamocortical circuits in NFLE.

Surgery in severe factor XIII deficiency: report of a case of epilepsy neurosurgery and review.

Factor XIII (FXIII) deficiency is a rare autosomal recessive congenital disorder of haemostasis, associated with a high risk of intracranial haemorrhage. Intracranial haemorrhage can result in neurological sequelae including seizure disorders. In some cases, medically intractable epilepsy led to epilepsy surgery. Little has been reported on the management of FXIII deficiency during surgery, and there is only a few data on the management, safety and efficacy of epilepsy surgery in the patients with haemostatic disorder. We report here an epilepsy neurosurgery in a case of severe FXIII deficiency.

[Focal cortical dysplasia possibly related to a probable prenatal ischemic injury]. / Dysplasie corticale focale liée à un probable accident ischémique anténatal.

Focal cortical dysplasias are a frequent etiology of partial seizure disorders refractory to medical treatment. We report the case of a patient with focal cortical dysplasia, confirmed by surgery, in association with ischemic cerebral lesions that possibly occurred during the intra-uterine development. This observation reinforces the hypothesis of a possible factor of causality between prenatal ischemia and anomalies of cortical development.

Cortical dysplasia: electroclinical, imaging, and neuropathologic study of 13 patients.

PURPOSE: The aim of this study was to correlate the electroclinical and radiologic data with the neuropathologic findings and surgical outcome in epileptic patients with epilepsy and Taylor's focal cortical dysplasia (TFCD) and to characterize further the abnormal intermediate filaments expression in the balloon cell present in the peculiar dysplasia. METHODS: We retrospectively selected 13 TFCD patients who underwent surgery for intractable epilepsy with the aim of removing the magnetic resonance (MR)-detectable lesion and/or the epileptogenic zone defined by stereoelectroencephalographic recordings. The surgical specimens were analyzed by means of routine neuropathologic and immunocytochemical studies. Antisera against different intermediate filaments also were used in serial adjacent sections to evaluate their coexpression in balloon cells. RESULTS: Histopathologic abnormalities typical of TFCD were found not only within the MR-visible lesions but also in most of the epileptogenic zones with no MR signal alterations. Furthermore, the MR-visible lesions contained a high proportion of cells with an abnormal expression of intermediate filament proteins. After a long follow-up, 10 of the patients are now seizure free. CONCLUSIONS: Our findings indicate that highly epileptogenic zones may correspond to tissue alterations not revealed by neuroimaging. Furthermore, the immunocytochemical data show that the dysplastic tissue detected by MR contained high concentrations of cells filled with abnormal intermediate filaments. The detected colocalization of neuronal and glial markers in balloon cells indicates a failure of cellular commitment during development.

Functional MRI assessment of the hemispheric predominance for language in epileptic patients using a simple rhyme detection task.

This study assesses the interest of a simple fMRI rhyme detection paradigm to determine hemispheric predominance for language in epileptic patients. Nineteen patients were examined. The findings derived from the fMRI examinations were compared with those obtained on the same patients using the Wada test, stereotactic intracerebral EEG stimulations and recordings, and/or video-EEG recordings. For the seventeen patients for whom language dominance could be assessed by means of at least one of the latter procedures, the fMRI examination provided concordant results in sixteen. In two patients, the hemispheric predominance for language could only be determined by fMRI. Nine patients underwent surgery subsequent to the fMRI examination. None of them exhibited any aphasic problems following surgery. The rhyme detection task used in the fMRI examination generates robust responses in the language areas, permits easy monitoring of the patient's task performance and can be easily undertaken by the epileptic patients. Thus, this study demonstrates that the fMRI rhyme detection paradigm is particularly well-suited for determining hemispheric language predominance in epileptic candidates for surgery.