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Biomedical subjects

M F Levesque

Publications and source records attributed to M F Levesque.

At least 19 recordsLinked to original sources
PubMed2000

Fetal and adult human CNS stem cells have similar molecular characteristics and developmental potential.

The mammalian central nervous system (CNS) contains multipotent stem cells that develop into neurons, astrocytes and oligodendrocytes. Our current data show that fetal and adult human CNS stem cell isolates display similar proliferation kinetics, differentiate into three major cell types of the nervous system and express similar sets of regulatory genes. However, each individual CNS stem cell isolate could be distinguished by its specific gene expression and developmental potential.

Astrocytes↗
PubMed1999

Presurgical contribution of quantitative stereotactic positron emission tomography in temporo limbic epilepsy.

BACKGROUND: We quantified the interictal metabolic changes associated with temporal lobe epilepsy by using an accurate stereotactic method. METHODS: We selected 16 patients who had proven unilateral focal or regional temporal onset defined by SEEG criteria. Each patient underwent stereotactic MRI and stereotactic [18 fluoro] fluorodeoxyglucose positron emission tomography (PET). RESULTS: Asymmetries (mean, +/- SD) were found in mesio-temporal structures: amygdala (-0.033+/-0.027, p = 0.0002), hippocampus (-0.035+/-0.032, p = 0.0006), and superior temporal gyrus (-0.036+/-0.032, p = 0.0004). Four of the sixteen patients had previously had unlocalized qualitative nonstereotactic PET analysis. CONCLUSIONS: The quantitative stereotactical PET method allows a higher resolution study of mesio-temporal structures.

Adolescent↗
PubMed1994

Comparisons of MEG, EEG, and ECoG source localization in neocortical partial epilepsy in humans.

In order to delineate the characteristics of epileptic spikes, 1946 different spikes were studied in 6 patients with complex partial epilepsy. Non-invasive MEG and EEG source analysis of interictal spikes were contrasted to ECoG localization, surgical outcome and presence of lesions on MRI. Results indicated that: (1) using the most frequent occurring spike topography patterns from a large sample of spikes improved goodness-of-fit values for both MEG and EEG localization, (2) when spike patterns could be appropriately matched on several successive MEG measurements to provide an adequate matrix (3 of 6 subjects), there was excellent agreement between MEG dipole sources and ECoG sources as well as surgical outcome and presence of MRI lesions, (3) EEG source analyses also gave good results but not as consistently as MEG.

Adult↗
PubMed1993

Single mossy fiber axonal systems of human dentate granule cells studied in hippocampal slices from patients with temporal lobe epilepsy.

Previous histological and immunocytochemical studies suggest that reorganization of the dentate granule cell axons, the mossy fibers, can occur in epileptic human hippocampus (Sutula et al., 1989; Houser et al., 1990; Babb et al., 1991) and in animal models of epilepsy (Tauck and Nadler, 1985; Sutula et al., 1988; Cronin et al., 1992). However, neuroanatomical analyses of the trajectory and morphology of reorganized axons are not yet available. The present study was conducted to investigate single dentate granule cell axonal systems in human epileptic hippocampus. Individual mossy fibers were directly visualized by injecting a tracer (biocytin or Lucifer yellow) intracellularly in hippocampal slices prepared from temporal lobes that were surgically removed from patients for treatment of intractable epilepsy. Two major arborization patterns were identified: (1) the parent axons extended to and coursed through the hilus toward CA3, leaving collaterals along their paths in the hilus (N = 19 neurons); (2) in addition to the aforementioned axonal system, collateral(s) branched from the parent axon near the soma and projected to the granule cell layer and molecular layer, forming an aberrant axonal pathway (N = 9 neurons). These aberrant collaterals bore large boutons similar to those of the hilar axons and formed extensive plexuses in the granule cell layer and/or in the molecular layer. The summed length of collaterals in the granular/molecular layers was 1110.8 microns on average, which was one-fourth of the total summed length of the mossy fibers (3698.5 microns on average). The size of the somata in neurons that had aberrant collaterals was significantly larger than that of neurons without such collaterals (p < 0.025). In four cases, filopodium-like fine processes were present near the axon hillock and proximal parts of the parent axon, suggesting that the aberrant collateral formation might be an ongoing process in these tissues. The lack of control slices from normal living human hippocampus makes it difficult to assess to what extent the present findings are epilepsy associated. However, the presence of aberrant mossy fiber collaterals in the hippocampi used in the present study has been confirmed by Timm's staining and/or dynorphin immunohistochemistry in comparison with nonepileptic autopsy material, indicating its relation to epilepsy (Babb et al., 1991, 1992). At present, there seems to be a consensus that the projection of mossy fiber collaterals to the supragranular layer is a rare occurrence in normal rats (Lorento de Nó, 1934; Claiborne et al., 1986; Seress et al., 1991; present study), normal monkeys (Seress et al., 1991), and normal humans (Houser et al., 1990).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Topographic mapping of somatosensory evoked potentials helps identify motor cortex more quickly in the operating room.

Median nerve somatosensory evoked potentials were recorded from exposed cerebral cortex during craniotomies. This technique is valuable when knowledge of the motor cortex location can influence surgical decisions about resection limits or biopsy sites. Two different recording techniques were compared: strips of electrodes and arrays of electrodes. The arrays recorded electrical potentials suitable for topographic mapping. We found that motor cortex could be identified more quickly when using the topographic mapping of SEPs from arrays. We conclude that topographic mapping of SEP from sensorimotor regions during craniotomies works well in general and can be done more quickly than the traditional electrode strip technique.

Adolescent↗
PubMed1992

Surgery of central sensory motor and dorsolateral frontal lobe seizures.

Ten patients who presented with dorsolateral or frontocentral seizures were studied with chronic subdural grid electrodes. Cortical mapping, sensory-evoked potentials and chronic electrocorticography were obtained for each patient. Seizures were classified as focal, regional or dipolar. At the time of explanation, a selective functional corticectomy was performed. Surgical outcome is presented at a mean follow-up of 36 months. Two patients are seizure-free and 7 patients had a significant reduction in seizure frequency. One patient had no change in seizure pattern. Dorsolateral frontal lobe seizures have a focal functional anatomy and can be surgically treated by selective cortectomy.

Adult↗
PubMed1992

Cortical sensory representation of the human hand: size of finger regions and nonoverlapping digit somatotopy.

Findings differ on cortical representation of fingers between human and animal studies, and on digit somatotopy among human studies. To resolve these differences, we mapped cortical sensory representation of each of the five digits and of median and ulnar nerves in three patients, using focal peripheral electrical shock stimuli. We compared locations and sizes of cortical regions among digits and nerves, using the model of a current dipole in a sphere applied to electrocorticography from subdural grids. Cortical representation was larger for the index finger than for the little finger and for the middle finger than for the ring finger, which are similar to findings in the monkey but different from Penfield's classic sensory homunculus. The thumb was larger than the middle finger, as in the homunculus. There was nonoverlapping somatotopy of all digits in each patient. These findings demonstrate a previously unrecognized similarity of cortical sensory organization of the fingers between humans and other primates.

Brain Mapping↗
PubMed1991

Increased NMDA responses and dendritic degeneration in human epileptic hippocampal neurons in slices.

To investigate physiological properties of epileptogenic neurons in relation to epileptic pathology, intracellular recording and intracellular dye injection after the recording were obtained in dentate granule cells in slices prepared from excised human epileptic hippocampus in which selective cell degeneration has been documented. Markedly prolonged excitatory postsynaptic potentials (EPSPs) were recorded in 67% of the total neurons sampled during perforant path stimulation. Such EPSPs were voltage dependent and sensitive to the NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid. Neurons that generated the increased N-methyl-D-aspartate (NMDA) responses were accompanied by abnormal dendritic morphology, i.e. loss of dendritic spines and development of beaded shafts. These findings suggest that an NMDA receptor-mediated toxic process that impinges specifically on dendritic components might take place in intractable epilepsy.

Adolescent↗
PubMed1991

Functional connections in the human temporal lobe. II. Evidence for a loss of functional linkage between contralateral limbic structures.

In a previous investigation of functional limbic pathways in the human mesial temporal lobe, we found evidence for strong connections between ipsilateral mesial temporal structures, but none for contralateral functional connections (Wilson et al. 1990). In the present study, we focused specifically upon the question of functional commissural linkages between these structures by systematic stimulation of a total of 390 electrode placements in 74 epileptic patients with temporal lobe depth electrodes implanted for surgical diagnosis. Eight standard electrode placement regions were targeted: amygdala, entorhinal cortex, anterior, middle and posterior hippocampus, subicular cortex, middle parahippocampal gyrus, and posterior parahippocampal gyrus. Three to six electrodes were implanted bilaterally in each patient, and each electrode was individually stimulated while recording from all the other sites. Out of the 390 electrodes stimulated, 78% were effective in evoking clear responses in adjacent ipsilateral structures, and 75% of 581 ipsilateral recording sites were responsive to stimulation. Only one of the stimulated electrode sites was effective in evoking responses in contralateral recording sites, and only two of 511 contralateral recording sites were responsive to that stimulation. The effective stimulation site was in presubicular cortex, and the responsive contralateral recording sites were in entorhinal and presubicular cortices. Response to this stimulation site was intermittent and variable in latency. The relative ease of obtaining functional verification of significant ipsilateral anatomical pathways in the human limbic system, and the sharply contrasting difficulty of functionally activating commissural pathways to contralateral limbic sites are discussed in the context of decreases in hippocampal contribution to commissural pathways in the primate brain compared to sub-primate mammals, and the significance of this change to normal limbic system function as well as to mechanisms of seizure spread in epilepsy.

Amygdala↗
PubMed1991

Functional anatomy of human hand sensorimotor cortex from spatiotemporal analysis of electrocorticography.

We measured chronic electrocorticography (ECoG) of sensorimotor cortex during contralateral median nerve stimulation in 6 patients with partial seizures evaluated for surgery. We analyzed the spatiotemporal structure of the somatosensory evoked response (SER) using multiple source modeling to investigate functional anatomy of its neuronal sources. Two dipole sources in postcentral gyrus explained the large majority of the first 60 msec of the SER, indicating a subregion of hand somatosensory cortex generating this activity. The source locations agreed with normal functional anatomy from cortical stimulations, intraoperative photographs, and postoperative neurological examinations after focal excisions. The time patterns of both sources were biphasic like the previously described N20-P30 and P25-N35 peaks. The spatiotemporal patterns of both sources overlapped. Spatiotemporal analysis with multiple dipole sources appears useful to determine the number, locations, and spatiotemporal field patterns of cortical regions active during peripheral somatosensory stimulation and reveals simplicity in the macroscopic functional anatomy of dynamic human sensorimotor cortex.

Adolescent↗
PubMed1991

Synaptic reorganization by mossy fibers in human epileptic fascia dentata.

This study was designed to identify whether synaptic reorganizations occur in epileptic human hippocampus which might contribute to feedback excitation. In epileptic hippocampi, (n = 21) reactive synaptogenesis of mossy fibers into the inner molecular layer of the granule cell dendrites was demonstrated at the light microscopic and electron microscopic levels. There was no inner molecular layer staining for mossy fibers in autopsy controls (n = 4) or in controls with neocortex epilepsy having no hippocampal sclerosis (n = 2). Comparing epileptics to controls, there were statistically significant correlations between Timm stain density and hilar cell loss. Since hilar neurons are the origin of ipsilateral projections to the inner molecular layer, this suggests that hilar deafferentation of this dendritic zone precedes mossy fiber reafferentation. Quantitative Timm-stained electron microscopy revealed large, zinc-labelled vesicles in terminals with asymmetric synapses on dendrites in the inner molecular and granule cell layers. Terminals in the middle and outer molecular layers did not contain zinc, were smaller and had smaller vesicles. These histochemical and ultrastructural data suggest that in damaged human epileptic hippocampus, mossy fiber reactive synaptogenesis may result in monosynaptic recurrent excitation of granule cells that could contribute to focal seizure onsets.

Animals↗
PubMed1991

Physiologic properties of human dentate granule cells in slices prepared from epileptic patients.

The neurophysiological properties of human dentate granule cells were studied in hippocampal slices prepared from patients undergoing surgical treatment for medically intractable temporal lobe epilepsy. In 24 neurons which were morphologically identified as dentate granule cells by intracellular staining with biocytin, there were 2 types of synaptic responses to perforant path stimulation: one showed an EPSP-IPSP sequence (n = 10) and the other showed prolonged EPSPs without accompanying hyperpolarizing IPSPs (n = 14). The prolonged EPSPs were markedly retarded by the application of an NMDA receptor antagonist, APV. Membrane properties of neurons showing the different classes of synaptic responses were similar in resting membrane potential (pooled average: -56.2 mV +/- 0.94 SEM) and spike amplitude (pooled average: 65.2 mV +/- 1.69 SEM). However, membrane resistance tended to be lower in neurons with prolonged EPSPs (31.8 M omega +/- 2.63 SEM) than in neurons that showed EPSP-IPSP responses (40.2 +/- 4.33) (P less than 0.05, Fisher). No spontaneous and/or evoked burst firing was observed. These data provide fuller information on the neurophysiological properties of human dentate granule cells in surgically resected epileptogenic hippocampus, implicating a role of NMDA receptor activation in human temporal lobe epilepsy.

Action Potentials↗
PubMed1991

Localization of partial epilepsy using magnetic and electric measurements.

Dipole methods applied to brain electric and magnetic fields have made several significant advances in investigation of epilepsy and sensorimotor cortex. The magnetoencephalogram (MEG) and the MEG-electroencephalogram (EEG) combination have contributed substantially. The MEG-EEG combination has shown a mean accuracy of somatosensory evoked response (SER) localization of the central fissure similar to electrocorticography (ECoG), resolution of ambiguity in ECoG of alternative configurations of hand sensorimotor cortex, and resolution of ambiguity of the causes of the difference between EEG and ECoG map patterns. MEG has shown simple dipolar maps of the temporal lobe interictal spike, localization estimates with about 6 mm error, and spatial separation of propagating multiple sources. MEG and EEG have shown a new neocortical propagation pathway in the temporal lobe, noninvasive estimates of the area of the spike focus, and complementary detection sensitivity. Application of spatiotemporal multiple dipole modeling in the simplest field using MEG has given a realistic quantification of spike zones. MEG and EEG have shown simple dipolar patterns for seizure origin, suggesting focality of some frontal seizures, and appears to increase EEG utility. Improved accuracy may result from a combined methodology including MEG and EEG. Dipole methods have potential utility as a noninvasive diagnostic procedure in epilepsy.

Brain Mapping↗
PubMed1990

Multimodality imaging of brain structures for stereotactic surgery.

An image analysis system was developed for stereotactic neurosurgery that allows the simultaneous display of brain images from different imaging devices obtained in different orientations. The system is based on a stereotactic frame and a microcomputer and features an easy user interface together with point registration and region of interest analysis in three-dimensional space. A dynamic multi-image environment allows for simultaneous display of magnetic resonance, computed tomography, digital subtraction angiography, and positron emission tomography images in multiple windows, adjusted for common coordinates with reference to stereotactic frame fiducial markers. Linkages between images allow information interchange between different modalities and different views: Points and regions defined in one image can be transferred to others, and cursor coordinates in one image can be calculated and dynamically projected in other images. Phantom studies show that the system distortions are minor and that the system is suitable for clinical use. The system provides exceptional advantages over previous imaging procedures for stereotactic surgery.

Angiography, Digital Subtraction↗