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Biomedical subjects

G Franck

Publications and source records attributed to G Franck.

At least 37 records · Page 2Linked to original sources

Medial temporal lobe metabolic impairment in dementia associated with motor neuron disease.

In the course of their disease certain patients with frontotemporal dementia (FTD) develop clinical features compatible with a motor neuron disease (FTD-MND). Previous reports have suggested that the functional pattern is similar in FTD and FTD-MND. However, some neuropathological studies suggest greater involvement of medial temporal regions in FTD-MND than in FTD. Using statistical parametric mapping (SPM96), we compared the metabolic patterns obtained at rest with positron emission tomography in 10 FTD patients and three FTD-MND patients with those obtained from 46 healthy subjects (HS). Mean age, duration of illness and dementia stage did not differ statistically between the FTD and FTD-MND groups. In comparison with HS, both groups showed frontal and anterior temporal hypometabolism at P<0.001. When the FTD-MND group was compared to the FTD group, significant hypometabolism was only observed in bilateral amygdala, bilateral hippocampus, and bilateral enthorinal and parahippocampal regions (Brodmann's areas, BA 28/36) at P<0.005. We found no significant differences in regional glucose uptake when FTD patients were contrasted to FTD-MND patients. Our results suggest statistically comparable frontal and lateral temporal hypometabolism in both conditions but greater impairment of medial temporal lobe activity in FTD-MND. Our results and a review of the literature support the hypothesis that there is a functional continuum between classical motor neuron disease (cMND), FTD-MND, and FTD.

Aged↗

Functional neuroanatomy of hypnotic state.

BACKGROUND: The aim of the present study was to describe the distribution of regional cerebral blood flow during the hypnotic state (HS) in humans, using positron-emission tomography (PET) and statistical parametric mapping. METHODS: The hypnotic state relied on revivification of pleasant autobiographical memories and was compared to imaging autobiographical material in "normal alertness." A group of 9 subjects under polygraphic monitoring received six H215O infusions and was scanned in the following order: alert-HS-HS-HS with color hallucination-HS with color hallucination-alert. PET data were analyzed using statistical parametric mapping (SPM95). RESULTS: The group analysis showed that hypnotic state is related to the activation of a widespread, mainly left-sided, set of cortical areas involving occipital, parietal, precentral, premotor, and ventrolateral prefrontal cortices and a few right-sided regions: occipital and anterior cingulate cortices. CONCLUSIONS: The pattern of activation during hypnotic state differs from those induced in normal subjects by the simple evocation of autobiographical memories. It shares many similarities with mental imagery, from which it differs by the relative deactivation of precuneus.

Adult↗

Impaired effective cortical connectivity in vegetative state: preliminary investigation using PET.

Vegetative state (VS) is a condition of abolished awareness with persistence of arousal. Awareness is part of consciousness, which itself is thought to represent an emergent property of cerebral neural networks. Our hypothesis was that part of the neural correlate underlying VS is an altered connectivity, especially between the associative cortices. We assessed regional cerebral glucose metabolism (rCMRGlu) and effective cortical connectivity in four patients in VS by means of statistical parametric mapping and [18F]fluorodeoxyglucose-positron emission tomography. Our data showed a common pattern of impaired rCMRGlu in the prefrontal, premotor, and parietotemporal association areas and posterior cingulate cortex/precuneus in VS. In a next step, we demonstrated that in VS patients various prefrontal and premotor areas have in common that they are less tightly connected with the posterior cingulate cortex than in normal controls. These results provide a strong argument for an alteration of cortical connectivity in VS patients.

Adult↗

Comparison of impaired subcortico-frontal metabolic networks in normal aging, subcortico-frontal dementia, and cortical frontal dementia.

Normal aging, progressive supranuclear palsy (PSP), and frontotemporal dementia (FTD) are characterized by different degrees of decline in frontal lobe functions. We used (18)FDG-PET and statistical parametric mapping (SPM96) to compare relative subcorticofrontal metabolic impairment at rest in 21 healthy elderly subjects (HES), 20 PSP patients, and 6 FTD patients. When HES were compared to 22 healthy young subjects, widespread decrease in metabolism was observed in bilateral medial prefrontal areas including anterior cingulate cortices, in dorsolateral prefrontal areas, in left lateral premotor area, in Broca's area, and in left insula. In PSP compared to the 43 healthy subjects (HS), we observed subcorticofrontal metabolic impairment including both motor and cognitive neural networks. Impairment of functional connections between midbrain tegmentum and cerebellar, temporal and pallidal regions was demonstrated in PSP as compared to HS. When comparing FTD to HS, glucose uptake was primarily reduced in dorsolateral and ventrolateral prefrontal cortices and in frontopolar and anterior cingulate regions. There was also bilateral anterior temporal, right inferior parietal, and bilateral striatal hypometabolism. Finally, FTD showed more severe striatofrontal metabolic impairment than PSP, while mesencephalothalamic involvement was only observed in PSP. Our data suggest that subcorticofrontal metabolic impairment is distributed in distinct subcorticocortical networks in normal aging, PSP, and FTD. Subcorticofrontal dementia in PSP is related to hypometabolism in discrete frontal areas, which are probably disconnected from certain subcortical structures. The concept of subcortical dementia is reinforced by our data, which show disrupted functional connections between mesencephalon and cerebellar cortex, inferior and medial temporal regions, and pallidum.

Adult↗

Fluorodopa uptake and glucose metabolism in early stages of corticobasal degeneration.

Fluorodopa (FDOPA) and fluorodeoxyglucose (FDG) PET was performed in six patients in early stages of corticobasal degeneration (CBD) and compared to Parkinson's disease (PD) patients with a similar degree of bradykinesia and rigidity and to healthy controls. Statistical parametric mapping analysis comparing CBD to controls showed metabolic decrease in premotor, primary motor, supplementary motor, primary sensory, prefrontal, and parietal associative cortices, and in caudate and thalamus contralateral to the side of clinical signs. Except for the prefrontal regions a similar metabolic pattern was observed when CBD was compared to PD. Putamen FDOPA uptake was decreased in both CBD and PD. Caudate FDOPA uptake in CBD patients was decreased contralateral to clinical signs when compared to controls, but was higher than in PD. In early stages of CBD, FDOPA and FDG PET patterns differed from those observed in PD. In CBD the asymmetry in FDOPA uptake was less pronounced than that of clinical signs or metabolic impairment.

Aged↗

Regional brain activity during tasks devoted to the central executive of working memory.

Most previous PET studies investigating the central executive (CE) component of working memory found activation in the prefrontal cortex. However, the tasks used did not always permit to distinguish precisely the functions of the CE from the storage function of the slave systems. The aim of the present study was to isolate brain areas that subserve manipulation of information by the CE when the influence of storage function was removed. A PET activation study was performed with four cognitive tasks, crossing conditions of temporary storage and manipulation of information. The manipulation of information induced an activation in the right (BA 10/46) and left (BA 9/6) middle frontal gyrus and in the left parietal area (BA7). The interaction between the storage and manipulation conditions did not reveal any significant changes in activation. These results are in agreement with the hypothesis that CE functions are distributed between anterior and posterior brain areas, but could also reflect a simultaneous involvement of controlled (frontal) and automatic (parietal) attentional systems. In the other hand, the absence of interaction between the storage and manipulation conditions demonstrates that the CE is not necessarily related to the presence of a memory load.

Adult↗

Modulating role of glucose on magnesium transport in rat erythrocytes.

Magnesium efflux from rat erythrocytes has been shown to be inhibited by a plasma fraction containing glucose. Therefore, we investigated the effect of D-glucose on erythrocyte magnesium transport. We show the inhibitory activity of this hexose on sodium (Na(+))-independent erythrocyte magnesium (Mg(2+)E) efflux. Inhibitory effects of D-mannose, 2-deoxy-D-glucose, and D-fructose on Mg(2+)E efflux also were demonstrated. Moreover, the suppression of the inhibitory activity of glucose on Mg(2+)E efflux was shown to be associated with the inhibition of glucose transport by cytochalasin B and phloretin. Together these data suggest a possible implication of the glucose carrier GLUT-1 in the regulation of Mg(2+) transport.

Journal Article↗

Methodological issues in a cost-of-dementia study in Belgium: the NAtional Dementia Economic Study (NADES).

The NAtional Dementia Economic Study (NADES) is an on-going prospective, one-year cohort study developed in Belgium to assess the socio-economic consequences of dementia in a group of patients and their caregivers (n = 400). Comparison is made with a group of subjects with cognitive impairment and no dementia (n = 100) and a group of subjects without any cognitive impairment (n = 100). Recruitment of subjects is based on screening of warning signs of dementia by general practitioners, followed by a Cambridge Mental Disorders of the Elderly Examination (CAMDEX) performed at home. This paper presents an overview of the study protocol and the rationale for basic design options, such as the choice of study population, screening strategy, and methods used for the case validation. It also presents preliminary results on the prevalence of dementia in general practice, the sensitivity and specificity of the warning signs as a screening test of dementia, and the validity of a computerised case ascertainment algorithm based on DSM-III-R criteria.

Aged↗

Early thalamic and cortical hypometabolism in adult-onset dementia due to metachromatic leukodystrophy.

A case of early-onset adult dementia with family history of dementia is reported, characterised by neuropsychological deficits, suggesting frontal involvement, with mild non specific white matter abnormalities on CT scan. Familial Alzheimer's disease was suspected but the neuropathological diagnosis on brain biopsy was metachromatic leukodystrophy. 18FDG-PET revealed a very peculiar pattern of metabolic impairment in thalamic areas, in medial and frontopolar regions, and in occipital lobes. Neuropsychological follow-up showed relatively stable difficulties of long-term memory and signs of frontal lobe dysfunction, similar to those observed in subcortical dementias. MRI subsequently showed periventricular leukoencephalopathy. The brain metabolic pattern observed in that case of metachromatic leukodystrophy was quite different from that reported in other types of dementia.

Adult↗

Functional neuroanatomy of human slow wave sleep.

The distribution of regional cerebral blood flow (rCBF) was estimated during sleep and wakefulness by using H215O positron emission tomography (PET) and statistical parametric mapping. A group analysis on 11 good sleepers (8 with steady slow wave sleep, SWS) showed a significant negative correlation between the occurrence of SWS and rCBF in dorsal pons and mesencephalon, thalami, basal ganglia, basal forebrain/hypothalamus, orbitofrontal cortex, anterior cingulate cortex, precuneus, and, on the right side, in a region that follows the medial aspect of the temporal lobe. Given the known decrease in global cerebral blood flow levels during SWS, these negative correlations suggest that rCBF is decreased significantly more in these cerebral areas than in the rest of the brain. The marked rCBF decreases in the pons, mesencephalon, thalamic nuclei, and basal forebrain reflect their close implication in the generation of SWS rhythms. The influence of these rhythms on the telencephalon usually are thought to be global and homogeneous. In contrast, our results show that rCBF is decreased more in some cortical areas (especially in orbitofrontal cortex) than in the rest of the cortex. We hypothesize that cellular processes taking place during SWS might be modulated differently in these regions. Given the functions of the ventromedial frontal areas, we surmise that SWS might be particularly critical for the adaptation of behavior to environmental pressures. This hypothesis is supported indirectly by results of sleep deprivation experiments.

Adult↗

Functional anatomy of verbal and visuospatial span tasks in Alzheimer's disease.

The aim of the study was to emphasize cerebral regions which subserve the performance of short-term memory tasks in patients with Alzheimer's disease. We correlated scores obtained on span tasks with cerebral metabolism measured at rest with positron emission tomography. Scores obtained on the digit span task correlated with glucose metabolism in a brain area centered on the premotor cortex and extending to the adjacent motor and parietal gyri. There exists some evidence suggesting that this area may subserve the sequential organization of material stored in short-term memory. In a secondary analysis, we also observed significant interregional correlations between left-sided brain areas which are part of the neural network subserving verbal working memory processes in healthy controls. These data suggest that individual performance on verbal span tasks in AD patients may essentially depend on the preservation of their ordination processing capacity. The absence of correlation with prefrontal regions suggests that AD patients might not spontaneously engage central executive resources to reach their maximal span score. For simultaneous visuospatial span task, the performance of patients correlated with posterior brain regions, and not with prefrontal cortices.

Aged↗

Anterior cingulate and motor network metabolic impairment in progressive supranuclear palsy.

Progressive supranuclear palsy is the prototype of subcortical dementia. Using positron emission tomography and statistical parametric mapping, we compared the glucose metabolic pattern obtained in this subcortical dementia to that observed in elderly healthy controls and in Alzheimer's disease, the prototype of cortical dementia. Progressive supranuclear palsy was characterized by a relative decrease of metabolism in anterior cingulate, adjacent supplementary motor area, precentral cortex, middle prefrontal cortex, midbrain tegmentum, globus pallidus, and ventrolateral and dorsomedial nuclei of thalamus. The data in progressive supranuclear palsy highlight predominant metabolic impairment in brain structures engaged in response selection, in attention for action, and in motor networks.

Aged↗

Mice selected for low and high blood magnesium levels: a new model for stress studies.

Extra- and intracellular magnesium levels have previously been shown to be genetically controlled in humans and in the mouse. To further study this genetic regulation, mice were selected from a heterogeneous population, for low (MGL mice) and high (MGH mice) red blood cell (RBC) magnesium values. These values diverged rapidly in the two strains, to reach a stable difference between the 14th and 18th generations. MGL mice also exhibited significantly lower plasma, kidney, and skull bone magnesium contents and higher urinary magnesium excretion and total brain weights. Moreover, in stressful conditions, MGL mice displayed a more aggressive behavior that the control MGH strain. Altogether, MGL mice showed a more restless behavior, a higher rectal temperature, and much higher brain (+17%) and urine (+200%) noradrenaline levels than the MGH animals. These strains, thus, constitute a new animal model for the study of magnesium metabolism and its relationships with catecholamines, stress sensitivity, and aggressive behavior.

Aggression↗

Is 11C-flumazenil PET superior to 18FDG PET and 123I-iomazenil SPECT in presurgical evaluation of temporal lobe epilepsy?

OBJECTIVE: To determine the contribution of 18FDG PET, 11C-flumazenil PET, and 123I-iomazenil SPECT to the presurgical evaluation of patients with medically intractable complex partial seizures. METHODS: Presurgical evaluation was performed in 23 patients, who were considered candidates for temporal lobe resective surgery (14 females and nine males with a median age of 34 (range 13 to 50) years). The presurgical diagnosis was based on seizure semiology as demonstrated with ictal video recording, ictal and interictal scalp EEG recordings, and MRI. RESULTS: Eighteen patients had convergent findings in clinical semiology, interictal and ictal EEG with scalp and sphenoidal electrodes, and MRI that warranted surgery without depth EEG (DEEG). In five patients with insufficient precision of localisation, DEEG with intracerebral and subdural electrodes was performed. MRI showed abnormalities in 22 out of 23 patients. Of these 22, 18 had mesial temporal sclerosis. This was limited to the mesial temporal lobe in four and more widespread in the temporal lobe in 14 patients. In one patient only enlargement of the temporal horn was found and in three others only white matter lesions were detected. 18FDG PET showed a large area of glucose hypometabolism in the epileptogenic temporal lobe, with an extension outside the temporal lobe in 10 of 23 patients. Only in one of these patients DEEG showed extratemporal abnormalities that were concordant with a significant extratemporal extension of hypometabolism in 18FDG PET. 18FDG PET was compared with the results of scalp EEG: in none of the patients was an anterior temporal ictal onset in scalp EEG related to a maximum hypometabolism in the mesial temporal area. By contrast, the region of abnormality indicated by 11C-flumazenil PET was much more restricted, also when compared with DEEG findings. Extension of abnormality outside the lobe of surgery was seen in only two patients with 11C-flumazenil and was less pronounced compared with the intratemporal abnormality. Both 18FDG PET and 11C-flumazenil PET reliably indicated the epileptogenic temporal lobe. Thus these techniques provide valuable support for the presurgical diagnosis, especially in patients with non-lesional MRI or non-lateralising or localising scalp EEG recordings. In those patients in whom phase 1 presurgical evaluation on the basis of classic methods does not allow a localisation of the epileptogenic area, PET studies may provide valuable information for the strategy of the implantation of intracranial electrodes for DEEG. Previous studies have suggested that 11C-flumazenil binding has a closer spatial relationship with the zone of ictal onset than the area of glucose hypometabolism, but this study suggests rather that the decrease in the 11C-flumazenil binding simply reflects a loss of neurons expressing the benzodiazepine-GABA receptor. 11C-flumazenil PET did not prove to be superior to 18FDG PET. CONCLUSION: In 21 patients sufficient material was obtained at surgery for a pathological examination. In 17 mesial temporal sclerosis, in one an oligodendroglioma grade B, in another a vascular malformation and in two patients no abnormalities were found. Although all 21 patients with pathological abnormality showed hypometabolic zones with 18FDG PET and a decreased uptake in 11C-flumazenil binding, there was no strong correlation between pathological diagnosis and functional abnormal areas in PET. Grading of medial temporal sclerosis according to the Wyler criteria showed no correlation with the degree of hypometabolism in either 18FDG or 11C-flumazenil PET. The interictal 123I-iomazenil SPECT technique was highly inaccurate in localising the lobe of surgery.

Adolescent↗

Functional neuroanatomy of human rapid-eye-movement sleep and dreaming.

Rapid-eye-movement (REM) sleep is associated with intense neuronal activity, ocular saccades, muscular atonia and dreaming. The function of REM sleep remains elusive and its neural correlates have not been characterized precisely in man. Here we use positron emission tomography and statistical parametric mapping to study the brain state associated with REM sleep in humans. We report a group study of seven subjects who maintained steady REM sleep during brain scanning and recalled dreams upon awakening. The results show that regional cerebral blood flow is positively correlated with REM sleep in pontine tegmentum, left thalamus, both amygdaloid complexes, anterior cingulate cortex and right parietal operculum. Negative correlations between regional cerebral blood flow and REM sleep are observed bilaterally, in a vast area of dorsolateral prefrontal cortex, in parietal cortex (supramarginal gyrus) as well as in posterior cingulate cortex and precuneus. Given the role of the amygdaloid complexes in the acquisition of emotionally influenced memories, the pattern of activation in the amygdala and the cortical areas provides a biological basis for the processing of some types of memory during REM sleep.

Adult↗