Biomedical subjects

L Garcia-Larrea

Publications and source records attributed to L Garcia-Larrea.

At least 19 recordsLinked to original sources

PubMed2006

Subthalamic nucleus stimulation in Parkinson's disease : anatomical and electrophysiological localization of active contacts.

OBJECTIVES: 1 - To assess the anatomical localization of the active contacts of deep brain stimulation targeted to the subthalamic nucleus (STN) in Parkinson's disease patients. 2 - To analyze the stereotactic spatial distribution of the active contacts in relation to the dorsal and the ventral electrophysiologically-defined borders of the STN and the stereotactic theoretical target. METHODS: Twenty-eight patients underwent bilateral high-frequency stimulation of the STN (HFS-STN). An indirect anatomical method based on ventriculography coupled to electrophysiological techniques were used to localize the STN. Clinical improvement was evaluated by Unified Parkinson's Disease Rating Scale motor score (UPDRS III). The normalized stereotactic coordinates of the active contact centres, dorsal and ventral electrophysiologically-defined borders of the STN were obtained from intraoperative X-rays images. These coordinates were represented in a three-dimensional stereotactic space and in the digitalized atlas of the human basal ganglia. RESULTS: HFS-STN resulted in significant improvement of motor function (62.8%) in off-medication state and levodopa-equivalent dose reduction of 68.7% (p < 0.05). Most of the active contacts (78.6%) were situated close to (+/- 1.6 mm) the dorsal border of the STN (STN-DB), while 16% were dorsal and 5.4% were ventral to it. Similar distribution was observed in the atlas. The euclidean distance between the STN-DB distribution center and the active contacts distribution center was 0.31 mm, while the distance between the active contacts distribution center and the stereotactic theoretical target was 2.15 mm. Most of the space defined by the active contacts distribution (53%) was inside that defined by the STN-DB distribution. CONCLUSION: In our series, most of the active electrodes were situated near the STN-DB. This suggests that HFS-STN could influence not only STN but also the dorsal adjacent structures (zona incerta and/or Fields of Forel).

Action Potentials↗

PubMed2005

Learning to react: anticipatory mechanisms in children and adults during a visuospatial attention task.

OBJECTIVE: To investigate the mechanisms underlying age-related improvement in response times during forewarned motor tasks, using reaction times (RTs) and event-related potentials (ERPs) during a variant of the Posner paradigm. METHODS: Children and adults reacted to visual targets preceded by a spatial cue. RESULTS: As expected, adults responded faster than children whatever the cue-target combination, but this advantage could not be explained by differences in attentional orienting to, or detection of, target stimuli. ERP differences between children and adults corresponded almost exclusively to the period preceding target stimuli, where adults, but not children, exhibited a slow negative wave that extended from the delivery of the cue to slightly beyond the presentation of the target. CONCLUSIONS AND SIGNIFICANCE: The timing, morphology and topography of this slow negativity corresponded to those of 'Contingent Negative Variation' and 'Readiness Potential' processes. We argue that the relative slowness of motor reactions in children during this task was not due to a deficit in spatial orienting or target evaluation, but rather to a failure in developing anticipatory and preparatory reactions in response to cues, i.e. a deficit in executive functions.

Adolescent↗

PubMed2004

An fMRI study of cortical representation of mechanical allodynia in patients with neuropathic pain.

OBJECTIVE: To investigate cerebral activity associated with allodynia in patients with neuropathic pain. METHODS: The brain responses of 27 patients with peripheral (5), spinal (3), brainstem (4), thalamic (5), lenticular (5), or cortical (5) lesions were studied with fMRI as innocuous mechanical stimuli were addressed to either the allodynic territory or the homologous contralateral region. RESULTS: When applied to the normal side, brush and cold rubbing stimuli did not evoke pain and activated a somatosensory "control" network including contralateral primary (SI) and secondary (SII) somatosensory cortices and insular regions. The same stimuli became severely painful when applied to the allodynic side and activated regions in the contralateral hemisphere that mirrored the "control" network, with, however, lesser activation of the SII and insular cortices. Increased activation volumes were found in contralateral SI and primary motor cortex (MI). Whereas ipsilateral responses appeared very small and restricted after control stimuli, they represented the most salient effect of allodynia and were observed mainly in the ipsilateral parietal operculum (SII), SI, and insula. Allodynic stimuli also recruited additional responses in motor/premotor areas (MI, supplementary motor area), in regions involved in spatial attention (posterior parietal cortices), and in regions linking attention and motor control (mid-anterior cingulate cortex). CONCLUSION: On a background of deafferentation in the hemisphere contralateral to stimuli, enhanced or additional responses to innocuous stimuli in the ipsilateral hemisphere may contribute to the shift of perception from innocuous toward painful and ill-defined sensations.

Basal Ganglia↗

PubMed2004

EFNS guidelines on neuropathic pain assessment.

In September 2001, a Task Force was set up under the auspices of the European Federation of Neurological Societies with the aim of evaluating the existing evidence about the methods of assessing neuropathic pain and its treatments. This review led to the development of guidelines to be used in the management of patients with neuropathic pain. In the clinical setting a neurological examination that includes an accurate sensory examination is often sufficient to reach a diagnosis. Nerve conduction studies and somatosensory-evoked potentials, which do not assess small fibre function, may demonstrate and localize a peripheral or central nervous lesion. A quantitative assessment of the nociceptive pathways is provided by quantitative sensory testing and laser-evoked potentials. To evaluate treatment efficacy in a patient and in controlled trials, the simplest psychometric scales and quality of life measures are probably the best methods. A laboratory measure of pain that by-passes the subjective report, and thus cognitive influences, is a hopeful aim for the future.

Europe↗

PubMed2003

Brain generators of laser-evoked potentials: from dipoles to functional significance.

In this work we review data on cortical generators of laser-evoked potentials (LEPs) in humans, as inferred from dipolar modelling of scalp EEG/MEG results, as well as from intracranial data recorded with subdural grids or intracortical electrodes. The cortical regions most consistently tagged as sources of scalp LERs are the suprasylvian region (parietal operculum, SII) and the anterior cingulate cortex (ACC). Variability in opercular sources across studies appear mainly in the anterior-posterior direction, where sources tend to follow the axis of the Sylvian fissure. As compared with parasylvian activation described in functional pain imaging studies, LEP opercular sources tended to cluster at more superior sites and not to involve the insula. The existence of suprasylvian opercular LEPs has been confirmed by both epicortical (subdural) and intracortical recordings. In dipole-modelling studies, these sources appear to become active less than 150 ms post-stimulus, and remain in action for longer than opercular responses recorded intracortically, thus suggesting that modelled opercular dipoles reflect a "lumped" activation of several sources in the suprasylvian region, including both the operculum and the insula. Participation of SI sources to explain LEP scalp distribution remains controversial, but evidence is emerging that both SI and opercular sources may be concomitantly activated by laser pulses, with very similar time courses. Should these data be confirmed, it would suggest that a parallel processing in SI and SII has remained functional in humans for noxious inputs, whereas hierarchical processing from SI toward SII has emerged for other somatosensory sub-modalities. The ACC has been described as a source of LEPs by virtually all EEG studies so far, with activation times roughly corresponding to scalp P2. Activation is generally confined to area 24 in the caudal ACC, and has been confirmed by subdural and intracortical recordings. The inability of most MEG studies to disclose such ACC activity may be due to the radial orientation of ACC currents relative to scalp. ACC dipole sources have been consistently located between the VAC and VPC lines of Talairach's space, near to the cingulate subsections activated by motor tasks involving control of the hand. Together with the fact that scalp activities at this latency are very sensitive to arousal and attention, this supports the hypothesis that laser-evoked ACC activity may underlie orienting reactions tightly coupled with limb withdrawal (or control of withdrawal). With much less consistency than the above-mentioned areas, posterior parietal, medial temporal and anterior insular regions have been occasionally tagged as possible contributors to LEPs. Dipoles ascribed to medial temporal lobe may be in some cases re-interpreted as being located at or near the insular cortex. This would make sense as the insular region has been shown to respond to thermal pain stimuli in both functional imaging and intracranial EEG studies.

Animals↗

PubMed2002

Role of operculoinsular cortices in human pain processing: converging evidence from PET, fMRI, dipole modeling, and intracerebral recordings of evoked potentials.

Insular and SII cortices have been consistently shown by PET, fMRI, EPs, and MEG techniques to be activated bilaterally by a nociceptive stimulation. The aim of the present study was to refer to, and to compare within a common stereotactic space, the nociceptive responses obtained in humans by (i) PET, (ii) fMRI, (iii) dipole modeling of scalp LEPs, and (iv) intracerebral recordings of LEPs. PET, fMRI, and scalp LEPs were obtained from normal subjects during thermal pain. Operculoinsular LEPs were obtained from 13 patients using deep brain electrodes implanted for presurgical evaluation of drug-resistant epilepsy. Whatever the technique, we obtained responses which were located bilaterally in the insular and SII cortices. In electrophysiological responses (LEPs) the SII insular contribution peaked between 150 and 250 ms poststimulus and corresponded to the earliest portions of the whole cerebral response. Group analysis of PET and fMRI data showed highly consistent responses contralateral to stimulation. On single-subject analysis, LEPs and fMRI activations were concentrated in relatively restricted volumes even though spatial sampling was quite different for both techniques. Despite our multimodal approach, however, it was not possible to separate insular from SII activities. Individual variations in the anatomy and function of SII and insular cortices may explain this limitation. This multimodal study provides, however, cross-validated spatial and temporal information on the pain-related processes occurring in the operculoinsular region, which thus appears as a major site for the early cortical pain encoding in the human brain.

Adult↗

PubMed2002

Cognitive effects of precentral cortical stimulation for pain control: an ERP study.

Electrical stimulation of the motor cortex (MCS) is a promising and increasingly used neurosurgical technique for the control of refractory neuropathic pain. Although its mechanisms of action remain unknown, recent functional imaging data suggest involvement of the thalamus, brainstem and anterior cingulate/orbitofrontal cortex. Since some of these areas are also implicated in higher cognitive functions, notably attentional processes, we analysed cognitive ERPs and behavioural performance during an "oddball" auditory detection task in patients submitted to this procedure. Eleven consecutive patients undergoing MCS because of neuropathic refractory pain, ranging in age from 25 to 71 years, were included in the study. ERPs were obtained in all cases both during the application ("MCS-on") and within the 10 min that followed discontinuation of the procedure ("MCS-off"). In five patients, ERPs could also be obtained just before the start of MCS. When the patients' sample was taken as a whole, there were no consistent effects of MCS on the ERPs. There was, however, a significant interaction of MCS action with the patients' age, reflecting a significant delay during MCS of the cognitive responses N2 and P3 (N200 and P300) in the group of patients older than 50 years exclusively. This effect was rapidly reversible after MCS discontinuation. No MCS-related changes were observed in the N1 component. At the individual level, the effect of MCS on the endogenous ERPs was highly variable, ranging from a total stability of ERPs (mostly in younger subjects) to latency differences of tens of milliseconds in the older group. These results, together with recent experiments showing P300 alteration during repetitive transcranial stimulation, suggest that motor cortex stimulation may interfere with relatively simple cognitive processes such as those underlying target detection, and that the risk of abnormal cognitive effects related to cortical stimulation may increase with age. Although the procedure appears on the whole remarkably safe, complementary neuropsychological studies in this category of patients are advised, as well as caution to possible adverse cognitive effects when using MCS in the elderly, notably in the presence of pre-existent cerebral lesions.

Adult↗

PubMed2001

Attention shifts and anticipatory mechanisms in hyperactive children: an ERP study using the Posner paradigm.

BACKGROUND: The aim of this study was to assess attentional, decisional, and motor processing stages during the performance of an attention shifting paradigm, both in normal children and children with attention-deficit/hyperactivity disorder (ADHD). METHODS: We recorded event-related potentials (ERPs) and performance measures during a variant of the Posner paradigm in 13 control subjects and 24 ADHD children. Subjects responded with a spatially concordant motor response to left or right visual targets, which could be either preceded by a spatial cue ("valid" = same side; "invalid" = opposite side) or presented uncued. RESULTS: Patients made significantly more errors than control subjects, with predominance of the anticipatory type. As compared to control subjects, ADHD children had faster reaction times, as well as a shortened interval between the N2 and P3 ERPs and the motor response. Patients also showed a decreased attentional priming effect on early sensory responses (P1). Finally, the slow negativity (contingent negative variation/readiness potential) that preceded the target in the "no cue" condition was absent in ADHD patients. CONCLUSIONS: The combined analysis of electrophysiological and behavioral data suggest a characteristic mode of response of ADHD in attention shifting tasks, characterized by "motor impulsivity" with release of motor responses before stimulus processing is adequately completed, as well as a lack of strategic planning/anticipatory mechanisms in the absence of warning stimulus. These deficits may be partly attributed to dysmaturation of executive frontal functions. In addition, a minor deficit in early attentional priming was also observed in ERPs, with no apparent behavioral counterparts.

Attention Deficit Disorder with Hyperactivity↗

PubMed2000

Dissociable ERP profiles for processing rules vs instances in a cognitive sequencing task.

A hotly debated question in cognitive neuroscience is whether individual instances of perceptual sequences, and the rules that describe them, are processed by the same brain mechanisms. We tested the hypothesis that such rules and instances are processed by dissociable brain mechanisms. We analyzed event-related brain potentials (ERPs) evoked during cognitive sequencing tasks that assessed surface (instance) vs abstract (rule) structure learning. Sequence instances ABCBAC and DEFEDF have different serial order or surface structure, but share the same rule or abstract structure, 123213. Nine healthy subjects were first trained to learn a set of surface and abstract structures in sequences of visually presented stimuli. During the subsequent ERP recording, for surface and abstract structures, they then discriminated between acceptable and unacceptable sequences, based on the pre-learned regularities. Abstract structure processing evoked a late positivity around 500 ms, which was not seen in the surface structure processing, supporting our hypothesis of dissociable processes. We discuss implications for the rule vs instance debate, and similarities between this late positivity and the P600 observed in previous studies of syntactic processing.

Adult↗

PubMed1999

The relation of putamen and caudate nucleus 18F-Dopa uptake to motor and cognitive performances in Parkinson's disease.

The contribution of striatal (caudate nucleus-putamen) dopaminergic deficiency to the severity of motor signs is well established in Parkinson's disease (PD), while its role in the occurrence of cognitive and mood changes remains unresolved. We therefore measured in 27 non-demented PD patients and 10 age-matched controls striatal uptake of [18F]-6-fluoro-L-Dopa (F-Dopa) with PET, and mood (Beck depression), memory (Grober-Buschke), frontal executive functions (verbal fluency and Wisconsin card sorting), and attentional processing of sensory stimuli (N2-P3 auditory event-related potentials--ERPs). Locomotor disability of patients was assessed by Hoehn and Yahr score and Unified Parkinson's Disease Rating Scale (UPDRS). ANOVA showed that memory, but neither frontal lobe functions nor ERPs, was significantly altered in PD patients, whereas indices of depression were found only in advanced PD. The F-Dopa rate constant Ki was significantly reduced in the striatum, more in putamen than caudate nucleus, and inversely correlated with disease duration. A significant inverse correlation was found between both putamen and caudate nucleus Ki and Hoehn and Yahr score, and between putamen--but not caudate nucleus Ki --and UPDRS motor score. Principal components analysis (PCA) of PD patients Ki values and mood, cognitive and ERP parameters gave a three-factor solution. Variables contributing to factor 1 were memory score and N2-P3 ERP latencies, those to factor 2 were striatal Ki values, and those to factor 3 frontal executive performances. Depression did not segregate with any variable. Our findings suggest that unlike locomotor disability, cognitive abilities and mood state of non-demented PD patients are for the most part unrelated to striatal dopaminergic depletion and may result from dysfunction of extra-striatal dopaminergic or from non-dopaminergic systems.

Adult↗

PubMed1999

Timing and characteristics of perceptual attenuation by transcranial stimulation: a study using magnetic cortical stimulation and somatosensory-evoked potentials.

Transcranial cortical magnetic stimulation (CMS) is a noninvasive, non-noxious procedure to induce perceptual attenuation when applied concomitant to sensory stimuli. To investigate the perceptual timing of simple stimulus features in the somatosensory modality, we applied right hemisphere CMS at different intervals following a stimulus delivered to the left hand. Different intervals between peripheral stimuli and CMS were defined according to the components of the somatosensory-evoked potentials (SEP), previously obtained in response to the same stimulus. Perceptual attenuation was maximal when CMS coincided with the primary cortical response (parietal N20 potential); conversely, perception of stimulus intensity was not modified when CMS was concomitant with the N200 and P300 potentials. Using small CMS intensities, a "perceptual dip" was observed when CMS arrived in coincidence with the N120 potential, a SEP response thought to be originated in part in the second somatic area. Our results support the view that both N200 and P300 are post-perceptual responses. The results also suggest that the cortical processes active during the N20 and N120 potentials may be essential for the conscious perception of somatosensory stimuli delivered to the hand.

Adult↗

PubMed1999

Precentral cortex stimulation for the treatment of central neuropathic pain: results of a prospective study in a 20-patient series.

The authors report a series of 23 patients with central neuropathic pain who were treated with the recently developed technique of precentral cortex stimulation (PCS). Of the 20 patients with a follow-up of more than 1 year (mean of 23 months) 25% had an excellent, 35% a good and 15% a fair relief of pain. In 25% the method failed. On the basis of these findings and the literature data (127 reported cases), the authors advocate PCS in patients with severe and medically refractory poststroke pain.

Adult↗

PubMed1998

Topographical reliability of mesio-temporal sources of interictal spikes in temporal lobe epilepsy.

PURPOSE: Localization of hippocampal paroxysmal activities in temporal lobe epilepsy (TLE) by means of dipole modeling has often been criticized because of the supposed inaccuracy of this technique in localizing deep sources of EEG signals. This study aimed at assessing the relevance of mesio-temporal dipoles, as identified by modeling of scalp recorded spikes in TLE. METHODS: Surface and depth EEG activities were simultaneously recorded using scalp and intracranial electrodes implanted through the foramen ovale (FO) in 3 patients with refractory TLE seizures. Intracranial FO spikes were used as triggers for scalp EEG averaging. The averaged signals were modeled by current dipoles, the localization of which were fused with patients' 3D-MRI. RESULTS: Individual FO spikes were undetectable on visual analysis of raw scalp EEG but were reflected by low-amplitude scalp EEG transients on averaged signal. Dipole modeling of this EEG deflection consistently identified a mesio-limbic source in a position close to that of the FO pole recording the intracranial spike with its maximal amplitude. CONCLUSION: This result suggests that mesio-temporal sources can be accurately localized by modeling the signals recorded on the scalp, thus validating the anatomical and clinical relevance of hippocampal sources identified by modeling scalp interictal averaged spikes in TLE.

Adult↗

PubMed1996

Source propagation of interictal spikes in temporal lobe epilepsy. Correlations between spike dipole modelling and [18F]fluorodeoxyglucose PET data.

Source localization methods were applied to interictal spikes from scalp EEGs and correlated with metabolic (PET scan) data in eight patients suffering from drug-resistant temporal lobe epilepsy (TLE). Dipolar sources, [18F]fluorodeoxyglucose (18FDG)-PET data and anatomical images (MRI) were projected into the same three-dimensional coordinates system. Averaged spikes were adequately modelled by two or three dipolar sources with different onset time of activation but overlapping activity (mean residual variance 3.4 +/- 2.1%). Although, in all patients, spike modelling demonstrated dipolar sources in both mesial and lateral temporal cortex, dipole propagation was consistent with the early involvement of only one of these two areas (mesio-temporal, five patients; lateral and polar neocortex, three patients). Six patients showed a unilateral interictal decrease in glucose uptake, as measured with 18FDG-PET, in the temporal lobe ipsilateral to the EEG spike focus. Temporal hypometabolism was bilateral in one patient and absent in the remaining case. When projected onto PET-scan slices, the dipolar sources of these patients were always included within the hypometabolic area. However, within the hypometabolic zone, the decrease in glucose uptake was not found to be more pronounced in regions containing dipoles. Therefore the spatio-temporal spread of neuronal hyperactivity underlying interictal spiking suggests the presence of preferential epileptogenic networks inside the hypometabolic temporal lobe. Fusion of bioelectric, metabolic and anatomical data proves to be a convenient way of summarizing multimodal information from non-invasive investigations in TLE patients entering an epilepsy surgery programme, and suggests that both interictal spike dipole modelling and 18FDG-PET data might be useful, as a complement to ictal electro-clinical data, in the presurgical evaluation of such patients.

Adult↗

PubMed1995

Long-term clinical, electrophysiological and urodynamic effects of chronic intrathecal baclofen infusion for treatment of spinal spasticity.

Seventeen patients with severe disabling spinal spasticity were selected and treated by chronic intrathecal baclofen infusion using an implanted programmable pump. Nine patients were tetraparetic, seven were paraplegic and one paraparetic. Patients were regularly followed for 5 to 69 months (mean 37.5 months). The clinical efficacy of baclofen was estimated by means of evaluation of: hypertonia, spasms, pain and functional disability. All patients experienced significant amelioration of quality of life secondary to reduction of hypertonia, spasms and pain related to contractures. Neurogenic pain improved in 3 cases and remained unchanged in 3 others. In patients whose motor functions were partially preserved, various degrees of motor improvement were detected. Electrophysiological recordings of Polysynaptic flexion reflexes (FR) were obtained to control conditions, and under intrathecal baclofen, in order to quantify the spinal excitability responsible for spontaneous or induced spasms. Flexion reflex threshold was increased and amplitude proved to be very significantly reduced by chronic baclofen infusion in all our patients. Twelve patients with neurogenic bladder dysfunction were also evaluated by a clinically oriented questionnaire and by quantitative urodynamic recordings, before and after pump implantation. In patients with normal micturition, this was not changed by intrathecal baclofen. In patients with spastic bladder, intrathecal baclofen produced a decrease of detrusor hypertonia and hyperactivity in 50% of cases, with reduction of leakage and increase in functional bladder capacity.

Adolescent↗

PubMed1995

Electrical stimulation of precentral cortical area in the treatment of central pain: electrophysiological and PET study.

The clinical, electrophysiological and haemodynamic effects of precentral gyrus stimulation (PGS) as a treatment of refractory post-stroke pain were studied in 2 patients. The first patient had a right hemibody pain secondary to a left parietal infarct sparing the thalamus, while the second patient had left lower limb pain developed after a right mesencephalic infarct. In both cases, spontaneous pain was associated with hyperpathia, allodynia and hypoaesthesia in the painful territory involving both lemniscal and extra-lemniscal sensory modalities in patient 1, extra-lemniscal sensory modality only in patient 2. Both patients were treated with electrical PGS by means of a 4-pole electrode, the central sulcus being per-operatively located using the phase-reversal of the N20 wave of somatosensory evoked potentials. No sensory side effect, abnormal movement or epileptic seizure were observed during PGS. The analgesic effects were somatotopically distributed according to the localization of electrode on motor cortex. A satisfactory long-lasting pain control (60-70% on visual analog scale) as well as attenuation of nociceptive reflexes were obtained during PGS in the first patient. Pain relief was less marked and only transient (2 months) in patient 2, in spite of a similar operative procedure. In this patient, in whom PGS eventually evoked painful dysethesiae, no attenuation of nociceptive RIII reflex could be evidenced during PGS. Cerebral blood flow (CBF) was studied using emission tomography (PET) with O-labeled water. The sites of CBF increase during PGS were the same in both patients, namely the thalamus ipsilateral to PGS, cingulate gyrus, orbito-frontal cortex and brainstem. CBF increase in brainstem structures was greater and lasted longer in patient 1 while patient 2 showed a greater CBF increase in orbito-frontal and cingular regions. Our results suggest that PGS-induced analgesia is somatotopically mediated and does not require the integrity of somatosensory cortex and lemniscal system. PGS analgesic efficacy may be mainly related to increased synaptic activity in the thalamus and brainstem while changes in cingulate gyrus and orbito-frontal cortex may be rather related to attentional and/or emotional processes. The inhibitory control on pain would involve thalamic and/or brainstem relays on descending pathways down to the spinal cord segments, leading to a depression of nociceptive reflexes. Painful dysesthesiae during stimulation have to be distinguished from other innocuous sensory side effects, since they may compromise PGS efficacy.

Aged↗

PubMed1994

Effects of GABAA receptors activation on brain glucose metabolism in normal subjects and temporal lobe epilepsy (TLE) patients. A positron emission tomography (PET) study. Part I: Brain glucose metabolism is increased after GABAA receptors activation.

Though gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the human central nervous system, the metabolic response to GABA system activation remains imperfectly known. We studied in vivo with positron emission tomography (PET) the variations of glucose metabolism in the human brain after stimulation of the GABAA receptors by systemic administration of the specific GABAA agonist, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP). These investigations were performed in three normal volunteers and as part of presurgical evaluation for temporal lobe epilepsy in six patients. While clinical and electroencephalographic (EEG) monitoring showed a sedative effect and sleepiness after THIP administration, glucose metabolism was paradoxically increased in grey matter structures, which are known to have a high density of GABAA receptors. These findings suggest that the pharmacological activation of GABA pathways, although inhibitory and producing a decrease of vigilance, increases the energetic demand at least during a phase of GABA agonist action, probably at the synaptic or at the glial cell level.

Adult↗

PubMed1994

Effects of GABAA receptors activation on brain glucose metabolism in normal subjects and temporal lobe epilepsy (TLE) patients. A positron emission tomography (PET) study. Part II: The focal hypometabolism is reactive to GABAA agonist administration in TLE.

Positron emission tomography (PET) using [18F]fluorodeoxyglucose (FDG) was used to study the metabolic response of focal hypometabolism to the administration of a specific GABAA agonist (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol), THIP, in six temporal lobe epilepsy (TLE) patients. After THIP injection, the increase of glucose metabolism in the hypometabolic focus was larger than the mean increase reported in the whole brain (Part I; Epilepsy Res., 19 (1994) 45-54). Within the hypometabolic focus, this increase was significantly higher in regions with the lowest basal metabolic level. This metabolic response in the hypometabolic focus, observed in the absence of any epileptic discharge during FDG accumulation and PET data acquisition, suggests that GABAA receptors are up-regulated or, at least, preserved in TLE.

Adult↗