Georges Franck

Experience-dependent changes in cerebral activation during human Rem sleep

The function of rapid-eye-movement (REM) sleep is still unknown. One prevailing hypothesis suggests that REM sleep is important in processing memory traces. Here, using positron emission tomography (PET) and regional cerebral blood flow measurements, we show that waking experience influences regional brain activity during subsequent sleep. Several brain areas activated during the execution of a serial reaction time task during wakefulness were significantly more active during REM sleep in subjects previously trained on the task than in non-trained subjects. These results support the hypothesis that memory traces are processed during REM sleep in humans.

Neural mechanisms of antinociceptive effects of hypnosis

BACKGROUND: The neural mechanisms underlying the modulation of pain perception by hypnosis remain obscure. In this study, we used positron emission tomography in 11 healthy volunteers to identify the brain areas in which hypnosis modulates cerebral responses to a noxious stimulus. METHODS: The protocol used a factorial design with two factors: state (hypnotic state, resting state, mental imagery) and stimulation (warm non-noxious vs. hot noxious stimuli applied to right thenar eminence). Two cerebral blood flow scans were obtained with the 15O-water technique during each condition. After each scan, the subject was asked to rate pain sensation and unpleasantness. Statistical parametric mapping was used to determine the main effects of noxious stimulation and hypnotic state as well as state-by-stimulation interactions (i.e., brain areas that would be more or less activated in hypnosis than in control conditions, under noxious stimulation). RESULTS: Hypnosis decreased both pain sensation and the unpleasantness of noxious stimuli. Noxious stimulation caused an increase in regional cerebral blood flow in the thalamic nuclei and anterior cingulate and insular cortices. The hypnotic state induced a significant activation of a right-sided extrastriate area and the anterior cingulate cortex. The interaction analysis showed that the activity in the anterior (mid-)cingulate cortex was related to pain perception and unpleasantness differently in the hypnotic state than in control situations. CONCLUSIONS: Both intensity and unpleasantness of the noxious stimuli are reduced during the hypnotic state. In addition, hypnotic modulation of pain is mediated by the anterior cingulate cortex. Language: en

Restoration of thalamocortical connectivity after recovery from persistent vegetative state

By use of H2(15)O positron emission tomography we have shown that functional connectivity between intralaminar thalamic nuclei and prefrontal and anterior cingulate cortices was altered during vegetative state but not after recovery of consciousness.

Cerebral glucose utilization during sleep-wake cycle in man determined by positron emission tomography and [18F]2-fluoro-2-deoxy-d-glucose method

Using the [18F]fluorodeoxyglucose method and positron emission tomography, we studied cerebral glucose utilization during sleep and wakefulness in 11 young normal subjects. Each of them was studied at least thrice: during wakefulness, slow wave sleep (SWS) and rapid eye movement sleep (REMS), at 1 week intervals. Four stage 3-4 SWS and 4 REMS fulfilled the steady state conditions of the model. The control population consisted of 9 normal age-matched subjects studied twice during wakefulness at, at least, 1 week intervals. Under these conditions, the average difference between the first and the second cerebral glucose metabolic rates (CMRGlu was: -7.91 +/- 15.46%, which does not differ significantly from zero (P = 0.13). During SWS, a significant decrease in CMRGlu was observed as compared to wakefulness (mean difference: -43.80 +/- 14.10%, P less than 0.01). All brain regions were equally affected but thalamic nuclei had significantly lower glucose utilization than the average cortex. During REMS, the CMRGlu were as high as during wakefulness (mean difference: 4.30 +/- 7.40%, P = 0.35). The metabolic pattern during REMS appeared more heterogeneous than at wake. An activation of left temporal and occipital areas is suggested. It is hypothetized that energy requirements for maintaining membrane polarity are reduced during SWS because of a decreased rate of synaptic events. During REMS, cerebral glucose utilization is similar to that of wakefulness, presumably because of reactivated neurotransmission and increased need for ion gradients maintenance.

Landau‐Kleffner Syndrome: A Clinical and EEG Study of Five Cases

Summary: : In five children with normal initial psychomotor development, a Landau‐Kleffner syndrome appeared at age 3–7 years. No neuroanatomy; lesions were noted. Aphasia and hyperkinesia were isolated in three patients and associated with global regression of higher cortical functions in one patient. Massive intellectual deterioration and psychotic behavior were associated with transient aphasia in one patient. The epilepsy (focal motor and generalized tonic‐clonic seizures, subclinical EEG focal seizures during sleep, and atypical absences) always regressed spontaneously or with antiepileptic drug (AED) treatment. The EEG in waking patients snowed focal and generalized spike‐wave discharges on a normal background rhythm. Discharge topography and pattern changed frequently. During sleep, discharges always increased. At some time during syndrome development, all patients had bilateral spike‐waves for 7gt;85% of the sleep period, while at other times the discharges were discontinuous or continuous but focal or unilaterally hemispheric. Discharge topography and abundance changed from night to night. The abnormal EEG and the impaired higher functions developed and regressed together, but not with strict temporal correlation. Our own experience suggests that the Landau‐Kleffner syndrome and epilepsy with continuous spike‐wave activity in slow‐wave sleep cannot be clearly differentiated. They may be different points on the spectrum of a single syndrome.

Cerebral metabolism during vegetative state and after recovery to consciousness

One way to approach the study of consciousness is to explore lesional cases in which impairment of consciousness is the prominent clinical sign. Vegetative state is such a condition wherein awareness is abolished whereas arousal persists. It can be diagnosed clinically soon after a brain injury and may be reversible (as in the following case report) or progress to a persistent vegetative state or death. The distinction between vegetative state and persistent vegetative state is that the second is defined as a vegetative state that has continued or endured for at least 1 month.1 We present a patient who developed a vegetative state after carbon monoxide poisoning and in whom we had the opportunity to measure brain glucose metabolism distribution during the vegetative state and after recovery to consciousness. Using [18F]fluorodeoxyglucose (FDG) PET and statistical parametric mapping (SPM) we compared both patient’s sets to a normal control population. Our findings offer an insight into the neural correlates of “awareness”, pointing to a critical role for posterior associative cortices in consciousness. Localisation of voxels in which cerebral glucose metabolism was impaired during vegetative state (in yellow) and after …

Cerebral Glucose Utilization During Stage 2 Sleep in Man

Using [18F]fluorodeoxyglucose method and positron emission tomography, we performed paired determinations of the cerebral glucose utilization at one week intervals during sleep and wakefulness, in 12 young normal subjects. During 6 of 28 sleep runs, a stable stage 2 SWS was observed that fulfilled the steady-state conditions of the model. The cerebral glucose utilization during stage 2 SWS was lower than during wakefulness, but the variation did not significantly differ from zero (mean variation: -11.5 +/- 25.57%, P = 0.28). The analysis of 89 regions of interest showed that glucose metabolism differed significantly from that observed at wake in 6 brain regions, among them both thalamic nuclei. We conclude that the brain energy metabolism is not homogeneous throughout all the stages of non-REMS but decreases from stage 2 SWS to deep SWS; we suggest that a low thalamic glucose metabolism is a metabolic feature common to both stage 2 and deep SWS, reflecting the inhibitory processes observed in the thalamus during these stages of sleep. Stage 2 SWS might protect the stability of sleep by insulating the subject from the environment and might be a prerequisite to the full development of other phases of sleep, especially deep SWS.

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 Brocas 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.

Effect of K+ ions on kinetic properties of the (Na+, K+)-ATPase (EC 3.6.1.3) of bulk isolated glial cells, perikarya and synaptosomes from rabbit brain cortex

Progress curves of the enzymatic reactions show that ATPases of bulk isolated glial cells, perikarya and synaptosomes exhibit hysteretic change. Initial velocities of enzyme activities were therefore obtained according to the equation valid for the hysteretic model. The (Na+, K+)-ATPase activities of the same brain fractions were measured before or after NaI treatment. Only glial and synaptosomal enzyme could be adequately extracted by using this procedure. Attempts to purify the (Na+, K+)-ATPase from brain perikarya by NaI extraction were unsuccessful. In order to determine the effect of the K+ ions on enzymic physiological efficiency (phys. eff.; i.e., the ratio Vmax/Kmapp) the variation of (Na+, K+)-ATPase activities from each brain fraction was measured as a function of Mg.ATP2- concentration in the presence of 5 and 20 mM K+ ions. High K+ ion concentrations (20 mM) increased the physiological efficiency of glial enzyme and decreased the same kinetic parameter in neuronal (perikaryal as well as synaptosomal) enzyme preparations. Results are discussed in relation to a possible distribution of distinct enzyme in different brain cell populations as well as a possible role of glial cells in an active regulation of K+ ion extracellular fluid in the CNS.

Cerebral Glucose Utilization During Sleep in Landau‐Kleffner Syndrome: A PET Study

Summary: : Three right‐handed male children (aged 5, 6, and 11 years) with signs, symptoms and/or history of the syndrome of acquired aphasia‐epilepsy (Landau‐Kleffner syndrome) were studied during drug‐induced, electroen‐cephalographically (EEG)‐monitored sleep by positron‐emission tomography (PET) and the [18F]fluorode‐oxyglucose (FDG) method. Our data demonstrate that in Landau‐Kleffner syndrome, cerebral glucose utilization is not normal during sleep. The metabolic pattern varied between the children but the metabolic disturbances always predominated over the temporal lobes. They were right‐sided, left‐sided, or bilateral. In the two first patients, EEG recordings showed continuous spike‐and‐wave discharges during sleep and a right‐greater‐than‐left asymmetry was observed in temporal areas. In patient 1, the asymmetry was associated with a relative increase of glucose utilization of the right posterior temporal region. In patient 2, the glucose utilization was relatively decreased in the left anterotemporal and left perisylvian regions. In patient 3, the sleep EEG showed no discharge and no significant asymmetry was observed; however, glucose utilization of both temporal lobes was decreased. Lower metabolic rates in subcortical structures than in cortex were also noted in the three children. This metabolic pattern may be related to the maturation of the central nervous system (CNS).