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Biomedical subjects

Lorella Minotti

Publications and source records attributed to Lorella Minotti.

17 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↗

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↗

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↗

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↗

Restricted frontomesial epileptogenic focus generating dyskinetic behavior and laughter.

PURPOSE: Substantial data are missing about the anatomic location of frontal regions supporting gelastic seizures. METHODS: We report the results of stereo-electro-encephalographic recordings performed over several distinct functional premotor and executive fields in a patient whose seizures were characterized by dyskinetic behavior and ictal laughter, in the absence of cerebral MRI abnormalities. RESULTS: The epileptogenic zone was circumscribed in the anterior and ventral part of the supplementary motor area and the underlying dorsal cingulate cortex. There were no or little spreading to cortical neighboring areas. The patient is seizure-free (follow-up of 27 months) after a stereotactic electric radiofrequency lesion of the epileptogenic focus. CONCLUSION: The present data suggest that pericingulate premotor areas are involved in the triggering of the motor component of laughter. In this case, the coexistence of paroxysmal dyskinesias during laughter might reflect the involvement of specific compartment(s) of the basal ganglia.

Adult↗

Epilepsy and hypothalamic hamartoma: look at the hand Pallister-Hall syndrome.

We report the case of a 29-year-old patient, who suffered from drug resistant laughing seizures since childhood. The clinical examination was normal, except for sequelae of hand and feet surgery during infancy for post-axial polydactyly. Cerebral MRI showed a hypothalamic hamartoma. The association of complex limb abnormalities with hypothalamic hamartoma lead to the diagnosis of Pallister-Hall syndrome. This syndrome is related to a mutation of gene GLI3, located on chromosome 7p13, and its inheritance is autosomal dominant. In the case of laughing seizures, a cerebral MRI should be performed to look for a hypothalamic hamartoma. The observation of such lesions indicates the necessity of standard radiographies of the hands and feet, to search for associated abnormalities. These findings might help to recognize a Pallister-Hall syndrome, thus allowing genetic counseling.

Adult↗

From hypothalamic hamartoma to cortex: what can be learnt from depth recordings and stimulation?

Patients having a hypothalamic hamartoma (HH) frequently present gelastic or dacrystic seizures, and they often later experience multiple additional seizure types which lead to a severe epileptic encephalopathy. There is now increasing evidence that the HH itself plays a crucial role in this syndrome, but the relationships between the lesion and the different types of seizures remain a questionable issue. Stereotactic intracerebral EEG recordings were performed in 5 patients suffering from a medically intractable epilepsy associated with a HH. The hamartoma was investigated in all cases, and various cortical areas were also evaluated in 4 of the 5 patients. The epileptic discharges arose and remained confined within the hamartoma in 3 of the 4 patients in whom laughing and crying episodes were recorded. In addition, interictal spikes were recorded from the hamartoma in 4 of the 5 patients, whereas the stimulation of the HH could reproduce gelastic or dacrystic episodes in 3. The three patients in whom other types of seizure were recorded showed that the latter were associated with cortical ictal discharges not affecting the HH. Ictal onset appeared either bifrontal, right fronto-central and lateral temporal, or bifrontal with a right side predominance. The cingulate gyrus was involved in all these 3 cases, and the lateralization of the ictal discharges was always ipsilateral to the predominating side of the hamartoma. Interestingly, these seizure types were sometimes immediately preceded by the laughing or crying attacks, as if ictal discharges within the hamartoma triggered those which seemed to originate in the cortex. Therefore, if these findings confirm the intrinsic epileptogenicity of HH, they also demonstrate that epileptic seizures associated with HH can exhibit different types of electroclinical patterns. We propose a speculative pathophysiology in which the mamillo-thalamo-cingulate tract would serve as a relay of HH discharges towards the cortex, the excitability of which would then progressively increase, first leading to cortical interictal epileptiform abnormalities and then to seizures of cortical origin. Whether this proposal of secondary epileptogenesis is valid or not remains a major issue, since it could provide arguments on the moment to discuss surgery.

Adolescent↗

Antiepileptic effect of high-frequency stimulation of the subthalamic nucleus (corpus luysi) in a case of medically intractable epilepsy caused by focal dysplasia: a 30-month follow-up: technical case report.

OBJECTIVE AND IMPORTANCE: Currently, some forms of epilepsy are resistant to both pharmacological and surgical interventions. As a result, there is a need for new therapeutic strategies. Because the nigral system modulates neuronal excitability in animal models of epilepsy, we considered therapeutic high-frequency stimulation of the subthalamic nucleus (STN). We were encouraged by the known relationship between the STN and the nigral system, as well as by our experience with high-frequency stimulation of the STN in Parkinsonian patients. CLINICAL PRESENTATION: A 5-year-old girl with pharmacologically resistant, inoperable epilepsy caused by focal centroparietal dysplasia underwent implantation with a permanent electrode in the left STN and was chronically stimulated. To date, we have followed up this patient for 30 months postoperatively. TECHNIQUE: High-frequency stimulation of the STN induced a significant voltage-dependent reduction (by 80%) in the number and severity of seizures. In addition, consistent improvement in both motor and cognitive functions was noted as a result of reduced postictal states. The effect was more prominent for seizures occurring in clusters (89% reduction) and during the day (88% reduction) than for those that occurred during sleep (53% reduction). CONCLUSION: This is the first report of epilepsy control using chronic high-frequency stimulation of the STN. Preliminary observations in three other operated patients (at 2, 12, and 18 mo) confirm these data. We think that high-frequency stimulation of the STN may hold significant future potential as a treatment for epilepsy, similar to its established role in the treatment of Parkinson's disease. This finding opens completely new experimental and therapeutic avenues for the treatment of surgically and medically intractable epilepsy.

Brain↗

Anatomy of the temporal pole region.

The temporopolar region is not clearly defined from an anatomical point of view. A line going through the rostral area of the inferior temporal, occipito temporal and superior temporal sulci is considered to represent its posterior limit on the lateral and inferior sides. On the internal side, this posterior limit corresponds to the rhinal sulcus, an anterior and internal extention of the collateral sulcus. From a cyto-architectonic point of view, the temporopolar region is caracterized by a dysgranular paralimbic cortex which ensures the transition between allo- and isocortical areas. The temporal pole is mainly connected with the amygadala, the hippocampus, the superior temporal gyrus, and the occipitobasal cortex, but also with the orbitary gyrus and the insula with which it forms the insulo-orbito-polar-temporo-complex. The temporal pole occupies the most rostral part of the temporal lobe and can only be accurately defined once the anatomy of the temporal lobe as a whole has been outlined. The architectonic configuration of this region as well as its connections with the limbic system, and the superior, orbital and insular temporal cortices make it a discrete temporal structure. Understanding the anatomical and functional organization of the temporal pole enables us to hypothesize about the role played by this structure in the pathogenesis of the forms of epilepsy originating in mesial temporal lobe structures.

Basal Ganglia↗

The role of the temporal pole in the genesis of temporal lobe seizures.

Failure of selective amygdalo-hippocampectomy strongly suggests that the so-called mesio-temporal lobe seizures do not always arise from the sole amygado-hippocampo-parahippocampal complex. Studies in temporal lobe epilepsies have shown that even in the presence of hippocampal sclerosis, the temporo-polar region (TP) is often altered, both histologically, anatomically and functionally. These findings are in accordance with our last ten years experience in stereotactic intracerebral EEG recordings (SEEG), during which we frequently observed the simultaneous involvement of both the amygdala (A), the hippocampus (Hc) and the TP at the onset of temporal lobe seizures. Recently, we have reviewed the SEEG findings of 25 patients with a final diagnosis of temporal lobe epilepsy, in whom both mesial, lateral and polar temporal lobe structures were investigated. The analysis of the most representative seizure in each patient showed that a low voltage fast activity was recorded in the TP either initially or within the first 5 seconds in 13/25 patients (TP group, 52%), while in the remaining 12 cases, ictal discharges started in the Hc and/or amygdala with a later involvement of the TP (AH group, 48%). Preliminary results of a further study conducted in 48 patients have confirmed the high frequency of early TP involvement (2/3 of the cases) in temporal lobe seizures, the clinical characteristics of which did not differ from ictal clinical findings usually described in the mesio-temporal lobe epilepsy syndrome. History of prolonged febrile convulsions and diagnosis of Hc sclerosis were more frequent in the AH group, while early consciousness impairment during seizures and anterior temporal white matter changes on MRI were more frequently observed in TP patients. However a clear-cut distinction between the two groups remains rather difficult in the absence of intracerebral recordings.

Amygdala↗

Deep brain stimulation in epilepsy with particular reference to the subthalamic nucleus.

Alternative methods, for the treatment of medically refractory epileptic patients, who cannot be treated by resective surgery, such as chronic deep brain neurostimulation, are under development. Such methods have been used in the cerebellum, various thalamic nuclei, and in the caudate nucleus. In Grenoble, encouraged by the suppressive effects of pharmacological or electrical inhibition of the STN on different types of seizure in animal models of epilepsy, and by our experience with STN high frequency stimulation (HFS) in patients with movement disorders, we have evaluated the high frequency stimulation of the subthalamic nucleus (STN HFS). STN HFS was performed in five patients suffering from medically intractable seizures and considered unsuitable for resective surgery. A 67% to 80% reduction in seizure frequency was observed in three patients, with a partial symptomatic epilepsy of the central region. An additional patient suffering from severe myoclonic epilepsy (Dravet syndrome) also responded to STN HFS, with a weaker reduction of seizure frequency. The fifth patient who suffered from an autosomal dominant frontal lobe epilepsy with insulo-frontal seizures did not show any improvement. These results suggest that stimulation of STN could be a promising treatment for patients with drug-resistant epilepsy who would not benefit from conventional surgery.

Adolescent↗