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Biomedical subjects

Alim-Louis Benabid

Publications and source records attributed to Alim-Louis Benabid.

15 recordsLinked to original sources

Acute psychotropic effects of bilateral subthalamic nucleus stimulation and levodopa in Parkinson's disease.

High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves the motor symptoms of Parkinson's disease (PD). Opposite changes in mood, such as mania or depression, have been reported after surgery, but it is not known whether these side effects are specifically related to STN DBS. To learn whether STN DBS also influences the limbic loop, we investigated acute subjective psychotropic effects related to levodopa or bilateral STN DBS. After a median postoperative follow-up of 12 months, 50 PD patients completed the Addiction Research Center Inventory (ARCI), assessing subjective psychotropic effects in four conditions: off-drug/on-stimulation; off-drug/off-stimulation; on-drug/off-stimulation; and on-drug/on-stimulation. Both levodopa and STN DBS improved all the ARCI subscales, indicating subjective feelings of well being, euphoria, increase in motivation, and decrease in fatigue, anxiety, and tension. A suprathreshold dose of levodopa was significantly more effective than STN DBS, using the same electrical parameters as for chronic stimulation, on four of the five ARCI subscales. We concluded that 1) both STN DBS and levodopa have synergistic acute beneficial psychotropic effects in PD, 2) the psychotropic effects of both treatments need to be considered in the long-term management of chronic STN DBS, and 3) the results indicate an involvement of the limbic STN in mood disorders of PD.

Activities of Daily Living↗

Bilateral subthalamic stimulation effects on oral force control in Parkinson's disease.

Dysarthria in Parkinson's disease (PD) consists of articulatory, phonatory and respiratory impairment. Bilateral subthalamic nucleus (STN) stimulation greatly improves motor disability, but its long-term effect on speech within a large group of patients has not been precisely evaluated. The aim of this study was to determine the effect of bilateral STN stimulation on oral force control in PD. We measured forces of the upper lip, lower lip and tongue in twenty-six PD patients treated with bilateral STN stimulation. Measurements of the articulatory organ force, as well as a motor evaluation using the Unified Parkinson's Disease Rating Scale (UPDRS), were made with and without STN stimulation. Maximal voluntary force (MVF), reaction time (RT), movement time (MT), imprecision of the peak force (PF) and the hold phase (HP) were all improved with STN stimulation during the articulatory force task, as well as the motor examination scores of the UPDRS. It seems that the beneficial STN stimulation-induced effect on articulatory forces persisted whatever the duration of post-surgical follow-up. However, dysarthria evaluated by the UPDRS was worse in two subgroups of patients with a one to two year and three to five year post-surgical follow-up, in comparison with a subgroup of patients with a three month follow-up. STN stimulation has a beneficial long-term effect on the articulatory organs involved in speech production, and this indicates that parkinsonian dysarthria is associated, at least in part, with an alteration in STN neuronal activity. Nevertheless, to confirm the persistence of the beneficial effect of STN stimulation on parkinsonian dysarthria, a longitudinal evaluation is still needed.

Adult↗

Effect of bilateral stimulation of the subthalamic nucleus on parkinsonian dysarthria.

Never was the effect of bilateral stimulation of the subthalamic nucleus (STN) evaluated quantitatively on all the components of speech production, that is articulation, respiration and phonation, at the same time. It is the purpose of this study which uses force measurements of the articulatory organs and acoustic analysis in 16 parkinsonian patients. With STN stimulation, reaction and movement time of the articulatory organs decreased and their maximal strength, as well as their precision increased. We also noted a large beneficial effect on voice with a significant improvement in respiratory and phonatory functions.

Adolescent↗

An unsupervised automatic method for sorting neuronal spike waveforms in awake and freely moving animals.

The present study introduces an approach to automatic classification of extracellularly recorded action potentials of neurons. The classification of spike waveform is considered a pattern recognition problem of special segments of signal that correspond to the appearance of spikes. The spikes generated by one neuron should be recognized as members of the same class. The spike waveforms are described by the nonlinear oscillating model as an ordinary differential equation with perturbation, thus characterizing the signal distortions in both amplitude and phase. It is shown that the use of local variables reduces the problem of spike recognition to the separation of a mixture of normal distributions in the transformed feature space. We have developed an unsupervised iteration-learning algorithm that estimates the number of classes and their centers according to the distance between spike trajectories in phase space. This algorithm scans the learning set to evaluate spike trajectories with maximal probability density in their neighborhood. Following the learning, the procedure of minimal distance is used to perform spike recognition. Estimation of trajectories in phase space requires calculation of the first- and second-order derivatives, and integral operators with piecewise polynomial kernels were used. This provided the computational efficiency of the developed approach for real-time application as required by recordings in behaving animals and in human neurosurgical operations. The new method of spike sorting was tested on simulated and real data and performed better than other approaches currently used in neurophysiology.

Action Potentials↗

Treatment results: Parkinson's disease.

Deep brain stimulation (DBS) is a neurosurgical treatment of Parkinson's disease that is applied to three targets: the ventral intermediate nucleus of the thalamus (Vim), the globus pallidus internas (GPi) and the subthalamic nucleus (STN). Vim DBS mainly improves contralateral tremor and, therefore, is being supplanted by DBS of the two other targets, even in patients with tremor dominant disease. STN and GPi DBS improve off-motor phases and dyskinesias. There is little comparative data between these procedures. The magnitude of the motor improvement seems more constant with STN than GPi DBS. STN DBS allows a decrease in antiparkinsonian drug doses and consumes moderate current. These advantages of STN over GPi DBS are offset by the need for more intensive postoperative management. The DBS procedure has the unique advantage of reversibility and adjustability over time. Patients with young-onset Parkinson's disease suffering from levodopa-induced motor complications but still responding well to levodopa and who exhibit no behavioral, mood, or cognitive impairment benefit the most from STN DBS. Adverse effects more specific of the DBS procedure are infection, cutaneous erosion, and lead breaking or disconnection. Intracranial electrode implantation can induce a hematoma or contusion. Most authors agree that the benefit to risk ratio of DBS is favorable.

Electric Stimulation Therapy↗

Intraoperative microrecordings of the subthalamic nucleus in Parkinson's disease.

Microelectrode recordings of single unit neuronal activity were used during stereotactic surgery to define the subthalamic nucleus for chronic deep brain stimulation in the treatment of Parkinson's disease. By using five parallel trajectories, often two to three microelectrodes allow us to recognize subthalamic nucleus (STN) neuronal activity. STN neurons were easily distinguished from cells of the overlying zona incerta and the underlying substantia nigra. During a typical exploratory track, we can observe a very low background noise in the zona incerta and almost complete absence of single cell recording. Penetration of the electrode tip into the STN is characterized by a sudden increase in background activity and single cell activity of spontaneously active neurons. The exit of electrode tip out of the STN corresponds to a decrease in background noise and a loss of single cell activity. Spontaneous neuronal activity increases again when the electrode tips enters the substantia nigra pars reticulata (SNr); however, the activity is less rich than in the STN, indicating a more cell-sparse nucleus. STN neurons are characterized by a mean firing rate of 42.30 +/- 22.00 spikes/sec (mean +/- SD). The STN cells exhibited irregular or bursty discharge pattern. The pattern of single cell activity in the SNr is a more regular tonic activity that can easily be distinguished from the bursting pattern in the STN. The most useful criteria to select a trajectory are (1) the length of an individual trajectory displaying typical STN activity, (2) the bursting pattern of activity, and (3) motor responses typical of the sensorimotor part of the nucleus. In conclusion, microelectrode recording of the subthalamic area improves the accuracy of targeting the STN.

Brain Mapping↗

Intraoperative micro- and macrostimulation of the subthalamic nucleus in Parkinson's disease.

Studying the clinical effects induced by electrical stimulation of the subthalamic nucleus (STN) area in a parkinsonian patient under local anesthesia is a mandatory step to determine the precise location of the final chronic electrode. Using multiple microelectrodes, preferably in a concentric parallel array allows a precise mapping of the STN region. The most reliable features to determine the suitable target are stimulation-induced dyskinesias and rigidity decrease at a low intensity without adverse effects or only at far higher intensities. New skills are needed to assess all stimulation-induced effects and interpret them in anatomo-functional terms.

Brain Mapping↗

Postoperative management of subthalamic nucleus stimulation for Parkinson's disease.

The postoperative neurologic management of patients with deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson' s disease is a complex dynamic process that involves a progressive increase in stimulation intensity and a parallel decrease in antiparkinsonian medication while assessing the interactions of both treatments. Neurologists responsible for postoperative management of patients receiving STN DBS must have expert knowledge of the electroanatomy of the subthalamic area and be familiar with the medical treatment of motor and nonmotor symptoms, including the management of long-term complications of levodopa treatment. Neurosurgeons who perform DBS need to understand the principles that guide the postoperative adaptation of treatment. This article defines guidelines for setting stimulation parameters, adapting drugs and managing adverse effects.

Antiparkinson Agents↗

Effects of subthalamic nucleus stimulation on actual and imagined movement in Parkinson's disease : a PET study.

BACKGROUND: PET studies in moderately affected Parkinson's disease (PD) patients reveal abnormal cerebral activation during motor execution and imagery, but the effects of subthalamic nucleus (STN) stimulation are not well established. OBJECTIVES: to assess the effect of STN stimulation on cerebral activation during actual and imagined movement in patients with advanced PD. METHODS: seven severely affected PD patients treated with bilateral STN stimulation were studied with PET and H(2)(15)O. The following conditions were investigated: (1). rest; (2). motor execution of a sequential predefined joystick movement with the right hand and (3). motor imagery of the same task. Patients were studied with and without left STN stimulation while right stimulator remained off. RESULTS: Without STN stimulation, the primary motor cortex was activated only during motor execution whereas the dorsolateral prefrontal cortex (DLPFC) was activated only during motor imagery. An activation of the supplementary motor area (SMA) was seen during both motor execution and motor imagery. Left STN stimulation during motor execution increased the regional cerebral blood flow (rCBF) bilaterally in the prefrontal cortex including DLPFC, in the left thalamus and putamen. In addition, a reduction of rCBF was noted in the right primary motor cortex, inferior parietal lobe and SMA. Under left STN stimulation, during motor imagery, rCBF increased bilaterally in the DLPFC and in the left thalamus and putamen and decreased in the left SMA and primary motor cortex. CONCLUSION: STN stimulation during both motor execution and imagery tends to improve the functioning of the frontal-striatal-thalamic pathway and to reduce the recruitment of compensatory motor circuits notably in motor, premotor and parietal cortical areas.

Aged↗

A community-centric internet portal for stereotactic and functional neurosurgery with a probabilistic functional atlas.

OBJECTIVE: This paper describes an Internet portal for stereotactic and functional neurosurgery with a probabilistic functional atlas (PFA) calculated from electrophysiological and neuroimaging data. This portal enables (1) data sharing among neurosurgeons; (2) the calculation of probabilistic functional maps of stereotactic target structures from a neurosurgeon's own data, optionally combined with data from other neurosurgeons, and (3) the construction and development of a PFA of the human brain by the neurosurgical community via the Internet. METHOD: The overall approach is done in three steps: (1) development and validation of the algorithm for PFA generation; (2) design and development of the portal for stereotactic and functional neurosurgery with tools for the rapid calculation, presentation, and use of the PFA, and (3) portal testing with the initial data acquired for 274 Parkinson's disease patients, 487 hemispheres, and 500 best contacts. This paper covers step 2 and some results from step 3. RESULTS: The Internet portal has been developed in Java and tested with the available data. Functions have been developed for: (1) data input, transfer, and editing; (2) data selection for PFA generation; (3) PFA generation; (4) PFA display and interactive manipulation, and (5) target planning. The portal has been put on the Internet for public use and so far more than 100 users downloaded it. CONCLUSION: The Internet portal for stereotactic and functional neurosurgery with a PFA potentially increases both the accuracy of targeting and the neurosurgeon's confidence. The portal may be useful for both experienced functional neurosurgeons who have studied numerous cases and novices in the field. The use of the PFA through this portal, and sharing and expanding its content by neurosurgeons represents a paradigm shift from manufacturer centric to community centric.

Anatomy, Artistic↗

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↗