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Bernard Bioulac

Publications and source records attributed to Bernard Bioulac.

At least 37 records · Page 2Linked to original sources
PubMed2004

High-frequency stimulation of both zona incerta and subthalamic nucleus induces a similar normalization of basal ganglia metabolic activity in experimental parkinsonism.

High-frequency stimulation (HFS) of the subthalamic nucleus (STN) alleviates dramatically motor symptoms in Parkinson's disease, and recently it has been suggested that zona incerta (ZI) stimulation might be as beneficial to patients. We used in situ cytochrome oxidase (CoI) mRNA hybridization to investigate and compare the effects of HFS of the STN and the ZI on metabolic activity of the STN, globus pallidus (GP), and substantia nigra reticulata (SNr) in normal rats as well as in rats with 6-hydroxydopamine (6-OHDA) lesion, an animal model of Parkinson's disease. In normal rats, HFS of the STN, as well as of the ZI, induced a significant decrease in CoI mRNA expression within the STN and SNr but an increase within the GP. In 6-OHDA rats, HFS of the STN reversed dopamine denervation-induced changes in the expression of CoI mRNA in the STN, SNr, and GP. Similar results were obtained with HFS of the ZI except for the STN, which showed only a trend toward normalization. These data suggest that the ZI, as well as the STN, are implicated in the functional mechanism of HFS supporting the involvement of GABA transmission for the reduction of neuronal activity in the basal ganglia output structures.

Animals↗
PubMed2004

Pathophysiology of obsessive-compulsive disorder: a necessary link between phenomenology, neuropsychology, imagery and physiology.

Obsessive-compulsive disorder (OCD) is characterized by repetitive intrusive thoughts and compulsive time-consuming behaviors classified into three to five distinct symptom dimensions including: (1) aggressive/somatic obsessions with checking compulsions; (2) contamination concerns with washing compulsions; (3) symmetry obsessions with counting/ordering compulsions; (4) hoarding obsessions with collecting compulsions; and (5) sexual/religious concerns. Phenomenologically, OCD could be thought of as the irruption of internal signals centered on the erroneous perception that "something is wrong" in a specific situation. This generates severe anxiety, leading to recurrent behaviors aimed at reducing the emotional tension. In this paper, we examine how the abnormalities in brain activity reported in OCD can be interpreted in the light of physiology after consideration of various approaches (phenomenology, neuropsychology, neuroimmunology and neuroimagery) that contribute to proposing the central role of several cortical and subcortical regions, especially the orbitofrontal cortex (OFC), the anterior cingulate cortex (ACC), the dorsolateral prefrontal cortex (DLPC), the head of the caudate nucleus and the thalamus. The OFC is involved in the significance attributed to the consequences of action, thereby subserving decision-making, whereas the ACC is particularly activated in situations in which there are conflicting options and a high likelihood of making an error. The DLPC plays a critical part in the cognitive processing of relevant information. This cortical information is then integrated by the caudate nucleus, which controls behavioral programs. A dysfunction of these networks at one or several stages will result in the emergence and maintenance of repetitive thoughts and characteristic OCD behavior.

Diagnostic Imaging↗
PubMed2004

Age, performance and sleep deprivation.

Young subjects are frequently involved in sleep-related accidents. They could be more affected than older drivers by sleep loss and therefore worsen their driving skills quicker, or have a different perception of their level of impairment. To test these hypotheses we studied variations of reaction time (RT), a fundamental prerequisite for safe performing, as measured by lapses, i.e. responses > or = 500 ms and self-assessment of performance and sleepiness after a night awake and after a night asleep in a balanced crossover design in young versus older healthy subjects. Ten young (20-25 years old) and 10 older volunteers (52-63 years old) were tested with and without 24 h of sleep deprivation. Without sleep deprivation, RTs were slower in older subjects than in the younger ones. However, after sleep deprivation, the RTs of young subjects increased while that of the older subjects remained almost unaffected. Sleepiness and self-perception of performance were equally affected in both age groups showing different perception of performance in the age groups. Our findings are discussed in terms of vulnerability to sleep-related accidents.

Accidents, Traffic↗
PubMed2004

Validation of Horne and Ostberg morningness-eveningness questionnaire in a middle-aged population of French workers.

As suggested by the authors, the Horne and Ostberg morning/evening questionnaire (MEQ) has never been adapted to evaluate a nonstudent population. The purpose of this study was to validate this MEQ in a sample of middle-aged workers by modifying only the cutoffs. It was administered in 566 non-shift-workers aged 51.2 to 3.2 years who presented no sleep disorders. According to the Home and Ostberg classification, the sample consisted of 62.1% morning type, 36.6% neither type, and 2.2% evening type. Multiple correspondence analysis, which determines the principal components, was performed on all MEQ items. Then an ascending hierarchical classification was applied to determine 3 clusters from these principal components. On the basis of these 3 clusters, new cutoffs were determined: evening types were considered as scoring under 53 and morning types above 64, thus giving 28.1% morning type, 51.7% neither type, and 20.2% evening type. As an external validation, eveningness was associated with later bedtime and waking-up time (more pronounced at the weekend), greater need for sleep, larger daily sleep debt, greater morning sleepiness, and ease of returning to sleep in the early morning. A positive correlation between age and morningness was again found. This study confirms that "owls" are not rare in a middle-aged sample. We conclude that this adapted MEQ could be useful when investigating age-related changes in sleep.

Biological Clocks↗
PubMed2004

Deep brain stimulation of the ventral caudate nucleus in the treatment of obsessive-compulsive disorder and major depression. Case report.

Obsessive-compulsive disorder (OCD) is an anxiety disorder associated with recurrent intrusive thoughts and repetitive behaviors. Although conventional pharmacological and/or psychological treatments are well established and effective in treating OCD, symptoms remain unchanged in up to 30% of patients. Deep brain stimulation (DBS) of the anterior limb of the internal capsule has recently been proposed as a possible therapeutic alternative in treatment-resistant OCD. In the present study, the authors tested the hypothesis that DBS of the ventral caudate nucleus might be effective in a patient with intractable severe OCD and concomitant major depression. Psychiatric assessment included the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the Hamilton Depression Rating Scale (HDRS), the Hamilton Anxiety Rating Scale (HARS), and the Global Assessment of Functioning (GAF) Scale for determining the symptom severity of OCD, depression, and anxiety as well as the quality of pychosocial and occupational functioning, respectively. Neuropsychological assessment consisted of a wide range of tests primarily exploring memory and executive functions. Deep brain stimulation of the ventral caudate nucleus markedly improved symptoms of depression and anxiety until their remission, which was achieved at 6 months after the start of stimulation (HDRS < or = 7 and HARS < or = 10). Remission of OCD (Y-BOCS < 16) was also delayed after 12 or 15 months of DBS. The level of functioning pursuant to the GAF scale progressively increased during the 15-month follow-up period. No neuropsychological deterioration was observed, indicating that DBS of the ventral caudate nucleus could be a promising strategy in the treatment of refractory cases of both OCD and major depression.

Caudate Nucleus↗
PubMed2004

Stuttering or reflex seizure? A case report.

Stuttering is characterized by involuntary syllabic repetitions and interruption in the smooth flow of speech. The exact cause of primary stuttering remains a matter of debate but a frontal dysfunction has been evoked. On the other hand, acquired stuttering is uncommon. We report a case of reflex epilepsy in which seizures were triggered by reading aloud or stressful conversation. Each paroxysmal event in left frontal region was associated clinically with a language disorder mimicking stuttering. Our observation suggests that reflex frontal focal epilepsy could be a putative etiology for acquired stuttering.

Aged↗
PubMed2003

Dual effect of high-frequency stimulation on subthalamic neuron activity.

Although it is well known that high-frequency stimulation (HFS) of the subthalamic nucleus (STN) alleviates the cardinal symptoms of Parkinson's disease, the underlying mechanisms are not fully understood. We investigated the effect of stimulation from low to high frequencies on rat STN neurons in naive and dopamine-depleted slices using whole-cell, current-clamp techniques and on-line artifact suppression. Stimulation at 10 Hz evoked 10 Hz single spikes but did not significantly modify ongoing STN activity. In contrast, at therapeutically relevant frequencies (80-185 Hz), stimulation had a dual effect: it fully suppressed STN spontaneous activity and generated a robust pattern of recurrent bursts of spikes, with each spike being time-locked to a stimulus pulse. Neither the suppression of spontaneous activity nor the generation of spikes was prevented by the antagonists of the metabotropic and ionotropic receptors of glutamate and gamma-aminobutyric acid. Tetrodotoxin, the Na+ channel blocker, suppressed all HFS-evoked spikes, whereas nifedipin, an L-type Ca2+-channel blocker, abolished the membrane oscillations underlying bursts. Therefore, we conclude that HFS drives the STN neuronal activity by directly activating the neuronal membrane. We suggest that this pattern may remove the deleterious activity of the basal ganglia network in the parkinsonian state and drive target neurons to a high-frequency state of activity, dependent on the characteristics of STN efferent synapses and resonant properties of target membranes.

Action Potentials↗
PubMed2003

Fatigue, sleep restriction, and performance in automobile drivers: a controlled study in a natural environment.

OBJECTIVES: To test the neurobehavioral consequences of sleep restriction combined with fatigue from long-distance driving (1000 Km/600 miles). DESIGN: Counterbalanced study involving 3 experimental conditions: laboratory after controlled habitual sleep (8.5 hours), driving after controlled habitual sleep (8.5 hours) (Road 1), and driving after reduced sleep (2 hours) (Road 2). SETTING: Sleep laboratory and open French highway. PARTICIPANTS: 10 male participants (mean age 22 years, range 18-24 years, mean driving distance per year 15000 Km/9000 miles) free of sleep disorders. MEASUREMENTS: Simple reaction time, prospective self-assessment of performance, and instantaneous fatigue and sleepiness ratings measured at 2-hour intervals. RESULTS: A two-way repeated ANOVA with time of day and condition indicated a significant main effect for time of day (p < 0.05). The interaction between the two factors (condition * time of day) was also significant (p < 0.05). The effects of time of day were significant only in the condition of driving after sleep restriction, (p < 0.05). Under sleep restriction, some drivers presented an increase of 650 milliseconds compared to the laboratory condition, representing an increase of 23 meters in breaking distance at a speed of 75 miles per hour. Correlation analyses showed a significant linear correlation between self-assessment and reaction time in the laboratory condition (r = -0.58, p < 0.01) but not in the road conditions. Self-ratings during the breaks showed a significant increase in instantaneous self-rated fatigue and sleepiness between Road 1 and Road 2 conditions (Wilcoxon's test, Z = - 6.47, p < 0.0001 and Z = - 6.26, p < 0.0001). CONCLUSIONS: Sleep restriction combined with fatigue significantly affects reaction time. The lack of correspondence between reaction time and prospective self-evaluation of performance suggests that self-monitoring in real conditions is poorly reliable.

Adolescent↗
PubMed2003

D5 (not D1) dopamine receptors potentiate burst-firing in neurons of the subthalamic nucleus by modulating an L-type calcium conductance.

Dopamine is a crucial factor in basal ganglia functioning. In current models of basal ganglia, dopamine is postulated to act on striatal neurons. However, it may also act on the subthalamic nucleus (STN), a key nucleus in the basal ganglia circuit. The data presented here were obtained in brain slices using whole-cell patch clamp. They reveal that D5 dopamine receptors strengthen electrical activity in the subset of subthalamic neurons endowed with burst-firing capacity, resulting in longer discharges of spontaneous or evoked bursts. To distinguish between D1 and D5 subtypes, the action of agonists in the D1/D5 receptor family was first investigated on rat subthalamic neurons. Single-cell reverse transcription-PCR profiling showed that burst-competent neurons only expressed D5 receptors. Accordingly, receptors localized in postsynaptic membranes within the STN were labeled by a D5-specific antibody. Second, agonists in the D1/D5 family were tested in mouse brain slices. It was found that these agonists were active in D1 receptor knock-out mice in a similar way to wild-type mice or rats. This proved that D5 rather than D1 receptors were involved. Pharmacological tools (dihydropyridines, omega-conotoxins, and calciseptine) were used to identify the target of D5 receptors as an L-type channel. This was reached via G-protein and protein kinase A. The action of dopamine on D5 receptors therefore shapes neuronal activity. It contributes to normal information processing in basal ganglia outside striatum. This finding may be useful in drug therapy for various disorders involving changes in STN activity, such as Parkinson's disease and related disorders.

Animals↗
PubMed2003

Compensatory regulation of striatal neuropeptide gene expression occurs before changes in metabolic activity of basal ganglia nuclei.

Compensatory mechanisms delay the appearance of parkinsonian symptoms. However, both the order of appearance and potential interactions of compensatory mechanisms acting within the nigrostriatal pathway as well as inside and outside the basal ganglia are not clear. We hypothesize that, after the striatal dopaminergic homeostasis breakdown, a modification in the expression of several striatal markers (neuropeptide precursors and dopamine receptors) may occur before a change in the activity of both globus pallidus (GP) and substantia nigra pars reticulata (SNr) in response to a partial nigrostriatal lesion. The present data show, in MPTP-treated mice, that preproenkephalin-A and preprotachykinin mRNA expression and D(3) receptor binding are modified without changes in cytochrome oxidase metabolic activity in both GP and SNr, respectively. These changes in neuropeptide expression would compensate for the dopamine depletion-induced changes in inhibitory GABAergic input from the striatum to GP and SNr. It also indicates that nondopaminergic compensatory mechanisms inherent to the basal ganglia are activated before those residing outside the basal ganglia.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2003

The circadian and homeostatic modulation of sleep pressure during wakefulness differs between morning and evening chronotypes.

The purpose of this study was to evaluate homeostatic and circadian sleep process in 'larks' and 'owls' under daily life conditions. Core body temperature, subjective sleepiness and waking electroencephalogram (EEG) theta-alpha activity (6.25-9 Hz) were assessed in 18 healthy men (nine morning and nine evening chronotypes, 21.4 +/- 1.9 years) during a 36-h constant routine that followed a week of a normal 'working' sleep-wake schedule (bedtime: 23.30 h, wake time: 07.30 h). The phase of the circadian rhythm of temperature and sleepiness occurred respectively, 1.5 h (P = 0.01) and 2 h (P = 0.009) later in evening- than in morning-type subjects. Only morning-type subjects showed a bimodal rhythm of sleep-wake propensity. The buildup of subjective sleepiness, as quantified by linear regression, was slower in evening than in morning types (P = 0.04). The time course of EEG theta-alpha activity of both chronotypes could be closely fitted by an exponential curve. The time constant of evening types was longer than that of morning types (P = 0.03), indicating a slower increase in sleep pressure during extended wakefulness. These results suggest that both the circadian signal and the kinetics of sleep pressure buildup differ between the two chronotypes even under prior naturalistic conditions mimicking the usual working day.

Adult↗
PubMed2003

Pattern of levodopa-induced striatal changes is different in normal and MPTP-lesioned mice.

While levodopa-induced neurochemical changes have been studied in animal models of Parkinson's disease, very little is known regarding the effects of levodopa administration in normal animals. The present study investigates the effects normal and MPTP-lesioned mice chronically treated with two different doses of levodopa. We assess changes in striatal dopamine (DA) receptor binding, striatal DA receptor mRNA levels and striatal neuropeptide precursor levels (preproenkephalin-A [PPE-A]; preprotachykinin [PPT]; preproenkephalin-B [PPE-B]). The extent of the lesion was measured by striatal DA transporter binding and stereological estimation of the number of tyrosine hydroxylase immunoreactive neurones in the substantia nigra pars compacta (SNc). In non-lesioned animals, chronic levodopa treatment induced an increase in PPE-A mRNA, whereas both D3R binding and PPE-B mRNA levels were dramatically increased in the lesioned animals in a dose dependent manner. The present results show that chronic levodopa administration may induce pathophysiological changes, even in the absence of a lesion of the nigro-striatal pathway, suggesting that the sensitization process involves predominantly the indirect striatofugal pathway in non-lesioned animals, whereas the direct pathway is primarily involved in lesioned animals.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2003

Electrophysiological and metabolic evidence that high-frequency stimulation of the subthalamic nucleus bridles neuronal activity in the subthalamic nucleus and the substantia nigra reticulata.

High-frequency stimulation (HFS) of the subthalamic nucleus (STN) has been shown to produce a dramatic alleviation of motor symptoms in patients with advanced Parkinson's disease. Its functional mechanism, however, remains obscure. We used extracellular recording and in situ cytochrome oxidase (CoI) mRNA hybridization to investigate the effects of HFS of the STN on neuronal activity of the STN and the substantia nigra reticulata (SNr) in normal rats and rats with 6-hydroxydopamine (6-OHDA) lesion of the substantia nigra compacta (SNc). To allow detection of spikes and analysis of firing activity, artifacts recorded during stimulation were scaled down using a template subtraction method. In both normal and lesioned rats, the activity of a majority of STN neurons was inhibited during stimulation. In the SNr, HFS also induced an inhibition of the activity of a majority of neurons in normal and lesioned rats. In situ hybridization histochemistry confirmed these results in that it showed a significant decrease in levels of CoI mRNA expression in the STN and SNr in both normal and lesioned rats during stimulation. These data afford an interesting insight into the functional mechanism of deep brain stimulation and support the hypothesis that HFS exerts an inhibitory influence on STN neuronal firing.

Animals↗
PubMed2003

[Inhibition and working memory: effect of acute sleep deprivation on a random letter generation task].

The literature contains inconsistent data on the effects of acute sleep deprivation on the superior cognitive functions. The primary purpose of this study is to determine the effectiveness of inhibition, one of the functions of the working memory executive centre (EC), over an extended, 36-hour waking period. Inhibition is a cognitive mechanism whereby individuals ignore non-relevant information recorded in their working memory. We also tested the effects of a 36-hour period of acute sleep deprivation on simple reaction time. Twelve young, healthy volunteers (M = 21.5 years, sigma = 2.3) performed a random generation task involving letters and a simple reaction time psychomotor test over four sessions held at 10-hour intervals. Each participant was assigned a "constant routine." Participants were kept awake in a prone position within a room whose environment was held strictly constant (light, noise, temperature, meals, etc.). This control procedure provided assurance that any variation in participant performance was solely caused by sleep deprivation. The random generation task, nearly two minutes in length, consisted in verbally producing a sequence of 100 letters in a random fashion (i.e. by inhibiting, for example, alphabetical order) and by keeping to a set rhythm. Our assumption was that capacity for inhibition diminished as the number of hours of sleep deprivation increased. The simple reaction test, 10 minutes in length, involved pressing a button as swiftly as possible to cause a black square to disappear from a screen. In this case our assumption was that acute sleep deprivation alters simple reaction time. Analysis of variance (ANOVA) through repeated measures using the "sessions" factor as an intra-subject variable showed no significant changes in randomization indices of the random generation task, contrary to analysis of average simple reaction times. Participants' reaction times deteriorated over the first two minutes of the test during the night they were deprived of sleep. It would seem that the contradictory results of previous studies of the effects of acute sleep deprivation on the inhibition function would be due to errors in factor identification. In conclusion, the inhibition function, as measured during the performance of a brief task, seems to remain intact during an extended, 36-hour waking period. Simple reaction time assessed by means of a brief psychomotor test is affected during a night of sleep deprivation. The working-memory inhibition executive function shows greater resistance to acute sleep deprivation than does psychomotor reaction time for the performance of short tasks.

Adolescent↗
PubMed2002

Disruption of the proprioceptive mapping in the medial wall of parkinsonian monkeys.

Parkinsonian patients present an impairment of proprioceptor-guided movement that could imply abnormal processing in the frontal mesial cortex. To test this hypothesis, we compared neuronal response to joint displacement in the supplementary and presupplementary motor areas of two monkeys, before and after the progressive establishment of an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian syndrome. After MPTP administration, neurons were activated by the passive movement of numerous joints in various directions and no longer simply by one or two joints in one direction. This impairment of the focused selection of proprioceptive inputs, imputable to dopamine depletion, could impede motor planning and thus contribute to akinesia.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2002

From single extracellular unit recording in experimental and human Parkinsonism to the development of a functional concept of the role played by the basal ganglia in motor control.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects the whole basal ganglia (BG). Various techniques have been used to study BG physiology and pathophysiology. Among these, extracellular single unit recording remains of particular importance. An impressive number of studies of BG electrophysiological activity have been carried out, both in non-human and in human primates, but the data collected show many omissions and disparities. BG activity has been well defined in the physiological situation, but remains far from clear in the Parkinsonian and virtually unexplored in the dopamine (DA)-replacement situation. This paper provides a brief synopsis of (i) recording techniques and (ii) BG electrophysiological activity in normal, Parkinsonian, and dopamine-replacement situations. We have restricted the data used to those obtained in BG structures of human and non-human primates. Only single unit recordings have been reported and four electrophysiological characteristics retained: mean firing frequency, firing pattern, periodic oscillation, and response to both passive and active movement. We have attempted to summarize (i) the commonly accepted characteristics of each BG structure in the three situations, (ii) discrepancies that exist, and (iii) missing elements. Then, the main successive theories aimed to explain the role played by BG in motor control are presented and discussed in the light of the most recently obtained results using the latest technological advances.

Animals↗