Quantification of brain cholinergic denervation in Alzheimer's disease using PET imaging with [18F]-FEOBV.

18F-fluoroethoxybenzovesamicol (FEOBV) is a new PET radiotracer that binds to the vesicular acetylcholine transporter. In both animals and healthy humans, FEOBV was found sensitive and reliable to characterize presynaptic cholinergic nerve terminals in the brain. It has been used here for we believe the first time in patients with Alzheimer's disease (AD) to quantify brain cholinergic losses. The sample included 12 participants evenly divided in healthy subjects and patients with AD, all assessed with the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) cognitive scales. Every participant underwent three consecutive PET imaging sessions with (1) the FEOBV as a tracer of the cholinergic terminals, (2) the 18F-NAV4694 (NAV) as an amyloid-beta tracer, and (3) the 18F-Fluorodeoxyglucose (FDG) as a brain metabolism agent. Standardized uptake value ratios (SUVRs) were computed for each tracer, and compared between the two groups using voxel wise t-tests. Correlations were also computed between each tracer and the cognitive scales, as well as between FEOBV and the two other radiotracers. Results showed major reductions of FEOBV uptake in multiple cortical areas that were evident in each AD subject, and in the AD group as a whole when compared to the control group. FDG and NAV were also able to distinguish the two groups, but with lower sensitivity than FEOBV. FEOBV uptake values were positively correlated with FDG in numerous cortical areas, and negatively correlated with NAV in some restricted areas. The MMSE and MoCA cognitive scales were found to correlate significantly with FEOBV and with FDG, but not with NAV. We concluded that PET imaging with FEOBV is more sensitive than either FDG or NAV to distinguish AD patients from control subjects, and may be useful to quantify disease severity. FEOBV can be used to assess cholinergic degeneration in human, and may represent an excellent biomarker for AD.

Sensorimotor adaptation in Parkinson's disease: evidence for a dopamine dependent remapping disturbance.

Sensorimotor adaptation is thought to involve a remapping of the kinematic and kinetic parameters associated with movements performed within a changing environment. Patients with Parkinson's disease (PD) are known to be affected on this type of learning process, although the specific role of dopamine depletion in these deficits has not yet been elucidated. The present study was an attempt to clarify whether dopamine depletion in PD may directly affect the capacity to internally reorganize the visuomotor remapping of a distorted environment. Fourteen PD patients were tested twice, while they were treated and while they were withdrawn from their regular levodopa treatment. Fourteen control subjects were also enrolled and tested twice. Two parallel forms of the Computed Mirror Pointing Task (CMPT), requiring making a reaching movement in a visually transformed environment (mirror inversion), were administered to each participant. Each of them had to perform 40 trials at each of the 2 testing sessions. At each trial, sensorimotor adaptation was evaluated by the initial direction angle (IDA), which reflects the direction of movement before any visually guided readjustment. Results revealed no IDA difference at baseline, between control subject and PD patients, whether they were treated or not. In all group, IDA values at that time were large, reflecting a tendency to make movements according to the real life visuomotor mapping (based on the natural direct vision). However, striking differences appeared during sensorimotor learning, in that IDA reduction along trials was poorer in patient not treated with levodopa than both control subjects and the same PD patient treated with levodopa. No difference was observed between the treated PD patients and control subjects. Given that IDA is thought to reflect the internal representation of the visuomotor mapping, it is concluded that dopamine depletion in PD would affects sensorimotor adaptation, in that it facilitates old and poorly adapted movements (real life mapping), instead of new and more adapted ones (mirror transformed mapping).

Raclopride-induced motor consolidation impairment in primates: role of the dopamine type-2 receptor in movement chunking into integrated sequences.

Results obtained in patients with schizophrenia have shown that antipsychotic drugs may induce motor learning deficits correlated with the striatal type-2 dopamine receptors (D(2)R) occupancy. Other findings suggest that the role of the striatum in motor learning could be related to a process of "chunking" discrete movements into motor sequences. We therefore hypothesized that a D(2)R blocking substance, such as raclopride, would affect motor learning by specifically disrupting the grouping of movements into sequences. Two monkeys were first trained to perform a baseline-overlearned sequence (Seq. A) drug free. Then, a new sequence was learned (Seq. B) and the overlearned sequence was recalled OFF-drug (Seq. A recall OFF-drug). The effect of raclopride was then assessed on the learning of a third sequence (Seq. C), and on the recall of the overlearned sequence (Seq. A recall ON-drug). Results showed that performance related to the overlearned sequence remained the same in the three experimental conditions (Seq. A, Seq. A recall OFF-drug, Seq. A recall ON-drug), whether the primates received raclopride or not. On the other hand, new sequence learning was significantly affected during raclopride treatment (Seq. C), when compared with new sequence learning without the effect of any drug (Seq. B). Raclopride-induced disturbances consisted in performance fluctuations, which persisted even after many days of trials, and prevented the monkeys from reaching a stable level of performance. Further analyses also showed that these fluctuations appeared to be related to monkeys' inability to group movements into single flowing motor sequences. The results of our study suggest that dopamine is involved in the stabilization or consolidation of motor performances, and that this function would involve a chunking of movements into well-integrated sequences.

Comparison between olanzapine and haloperidol on procedural learning and the relationship with striatal D2 receptor occupancy in schizophrenia.

The striatum is known to play a primary role in procedural learning. In this study, the authors simultaneously assessed the effects of two antipsychotic drugs on procedural learning and on striatal dopamine (D2) receptor occupancy. Twenty-seven patients receiving either olanzapine or haloperidol as antipsychotic medication were assessed with the Computed Visual Tracking Task (CVTT) and Single Photon Emission Computed Tomography (SPECT) following the administration of Iodine 123-IBZM (123I-IBZM), a radioligand with a high affinity and specificity for the D2 receptors. The results showed poorer procedural learning in the haloperidol-treated patients than in normal control subjects, while no difference could be found between olanzapine-treated patients and normal control subjects. In the haloperidol but not the olanzapine group, significant correlations were found between procedural learning deficits and striatal D2 receptor occupancy. However, there was no significant difference in D2 receptor occupancy between olanzapine- and haloperidol-treated patients, and this may be related to the high doses of olanzapine and low doses of haloperidol administered. The authors concluded that: 1) striatal D2 receptor blockade may alter procedural learning in humans; and 2) olanzapine may have a protective effect on procedural learning, even at doses that produce striatal D2 receptor occupancy as high as that found with haloperidol. This protective effect of olanzapine may be related to its atypical pharmacological properties.

Association between waking EEG slowing and REM sleep behavior disorder in PD without dementia.

OBJECTIVE: To compare nondemented patients with Parkinson's disease (PD) with and without REM sleep behavior disorder (RBD) to healthy controls on quantitative EEG characteristics for both wakefulness and REM sleep. METHODS: Fifteen patients with PD (7 patients with polysomnographic-confirmed RBD [PD-RBD] and 8 patients without RBD [PD-NRBD]) and 15 healthy control subjects were studied. Each subject underwent a quantitative EEG analysis of both wakefulness and REM sleep. RESULTS: During wakefulness, patients with PD-RBD showed a higher theta power in frontal, parietal, temporal, and occipital regions in comparison to patients with PD-NRBD and control subjects. Moreover, a slowing of the dominant occipital frequency was observed only in patients with PD-RBD (p < 0.02). Patients with PD-NRBD did not present any slowing of the EEG. No between-group difference in quantitative REM sleep EEG was observed. CONCLUSIONS: This study demonstrates that the EEG slowing reported during wakefulness in nondemented patients with PD is strongly related to the presence of RBD.

REM sleep behavior disorder and REM sleep without atonia in Parkinson's disease.

OBJECTIVE: To determine the frequency of REM sleep behavior disorder (RBD) among patients with PD using both history and polysomnography (PSG) recordings and to further study REM sleep muscle atonia in PD. BACKGROUND: The reported occurrence of RBD in PD varies from 15 to 47%. However, no study has estimated the frequency of RBD using PSG recordings or analyzed in detail the characteristics of REM sleep muscle atonia in a large group of unselected patients with PD. METHODS: Consecutive patients with PD (n = 33) and healthy control subjects (n = 16) were studied. Each subject underwent a structured clinical interview and PSG recording. REM sleep was scored using a method that allows the scoring of REM sleep without atonia. RESULTS: One third of patients with PD met the diagnostic criteria of RBD based on PSG recordings. Only one half of these cases would have been detected by history. Nineteen (58%) of 33 patients with PD but only 1 of 16 control subjects had REM sleep without atonia. Of these 19 patients with PD, 8 (42%) did not present with behavioral manifestations of RBD, and their cases may represent preclinical forms of RBD associated with PD. Moreover, the percentage of time spent with muscle atonia during REM sleep was lower among patients with PD than among healthy control subjects (60.1% vs 93.2%; p = 0.003). CONCLUSIONS: RBD and REM sleep without atonia are frequent in PD as shown by PSG recordings.

Behavioral disorganization in schizophrenia during a daily activity: the kitchen behavioral scoring scale.

Executive dysfunction has been extensively described in schizophrenia and has been found to correlate with the negative symptoms of the disease. However, executive dysfunction is usually assessed by cognitive tests, and these are not necessarily good predictors of an individual's daily functioning. This study aimed to discover whether executive dysfunction in schizophrenia can be measured by analyzing a daily routine such as cooking a meal. Behavior was scored on the basis of the optimal sequence of macrostructures (order of dishes) and microsteps (order of actions) that must be performed to prepare the meal in a minimum of time and with the smallest delay between the completion of the first and last dishes. The results showed that patients with schizophrenia make macrostructure but not micro-step sequencing errors. The number of repetitions and omissions and the delay between the completion of the first and last dish were all greater in patients than in control subjects. In patients with schizophrenia, but not in normal controls, these behavioral malfunctions were significantly correlated with both negative symptoms and performance on the executive tasks. Poor performance on the memory tests was not correlated with the behavioral malfunction. Therefore, daily functioning in schizophrenia may be specifically influenced by executive dysfunction in schizophrenia, and this can be quantitatively assessed with a behavioral scale of action sequences.

[Rapid-eye-movement sleep disorders in Parkinson's disease]. / Les troubles du sommeil paradoxal dans la maladie de Parkinson.

During the past 10 years, there has been an increasing interest in the study of rapid-eye-movement (REM) sleep in neurodegenerative diseases and more particulary in Parkinson's disease (PD). This interest is justified by the strong association observed between these diseases and REM sleep behavior disorder (RBD). In the first section of this paper, a critical review of the literature on the presence of REM sleep disorders in PD is presented. Studies that show an association between PD and RBD are reviewed. Studies that report the presence of other REM sleep disorders in PD (short latency, abnormal length and/or proportion of REM sleep, increasing occurrence of hallucinations) are then discussed. Limitations of the criteria proposed by Rechtschaffen et Kales (1968) for the quantification of REM sleep are also presented. Some authors believe that dopaminergic (DA) agents used in the treatment of PD (levodopa, bromocriptine, pergolide, pramipexole and selegiline) could be a responsable factor for the occurence of REM sleep disorders observed in this disease. The literature concerning the impact of these DA agents on human REM sleep is therefore critically reviewed. It is concluded that DA agents cannot explain on their own the presence of REM sleep disorders in PD. Other causes, among which the disturbance of some neurochemical systems linked to the neuropathological process of the disease, must be considered in order to explain these REM sleep disorders. In the second section of this paper, we present the different pathophysiological hypotheses proposed to explain REM sleep disorders in PD, such as a dysfunction of the cholinergic, noradrenergic, serotonergic, dopaminergic or GABAergic neurons. Emphasis is placed on the role of cholinergic neurons of the pedunculopontine and laterodorsal tegmental nuclei, structures shown to be particularly impaired in PD. Neurophysiological, neuroanatomical and neuropharmacological studies demonstrate that these neurons are strongly implicated in the different REM sleep parameters (muscular atonia, electroencephalographic desynchronisation, ponto-geniculo-occipital spikes). Finally, future research directions are proposed.

Pattern of intrusions in verbal recall: comparison of Alzheimer's disease, Parkinson's disease, and frontal lobe dementia.

Although some researchers have suggested that intrusions in word list learning are more frequent in Alzheimer's disease, recent studies have shown that this might not be true. In fact, intrusions are common in many neurological degenerative diseases. The goal of the present study was to examine the types of intrusions made by three groups of patients, namely patients with Parkinson's disease (PD), Alzheimer's disease (AD), and dementia with prominent frontal lobe semiology (FD). Although PD patients learned more words (trials 1 to 5 on the RAVLT) than the two other groups, there was no significant difference in the total number of intrusions. However, significant differences between groups were observed for nonrelated intrusions, the proportion of PD patients (15.4%) being lower than the proportion of AD (45.5%) and FD (45.8%) patients with this type of intrusions. No other type of intrusions (same category, recurring, phonemic) significantly differentiated between the three groups. The proactive interference effect (PI), measured as the difference between first recall of list A and list B recall, was stronger in PD than in the two other groups, reflecting the strong positive correlation between total number of words recalled on the RAVLT and severity of the PI effect. Prior list intrusions (intrusions from list A while recalling list B items) were significantly more pronounced in FD than in the two other groups. Finally, free associations (series of intrusions related to one another but not to the target items) were observed almost exclusively in FD patients. These findings illustrate some qualitative differences between various neurological degenerative diseases. They also stress the marked similarities between AD and FD with regards to verbal learning.

[Hypofrontality and negative symptoms in schizophrenia: synthesis of anatomic and neuropsychological knowledge and ecological perspectives]. / Hypofrontalité et symptômes négatifs dans la schizophrénie: synthèse des acquis anatomiques et neuropsychologiques et perspectives écologiques.

Cognitive deficits in schizophrenia have been observed with neuropsychological tests of executive function, traditionally considered sensitive to frontal lobe damage. These impairments affect planning abilities, as well as the aptitude to initiate and regulate a goal-directed behaviour. On the other hand, negative symptoms of schizophrenia are widely suspected to reflect a frontal lobe dysfunction. Based on a review of a hundred papers, the present article analyses the anatomical and neuropsychological evidence of disturbed frontal lobe functioning in patients with negative schizophrenic symptoms. The phenomenological similarity of some schizophrenic symptoms to the clinical features of patients with prefrontal injury inspired the hypothesis of damaged frontal lobe in the former disorder. The morphological findings of neuroimaging studies brought inconsistent conclusions, with some researchers noting no differences between patients and control subjects while others observing reduced prefrontal volumes in schizophrenia. The functional neuroimaging demonstrated a reduced frontal blood flow relative to the general cerebral perfusion in patients with schizophrenia. Even though the overall neuroimaging literature provides reliable evidence of frontal impairment in schizophrenia, the average magnitude of the difference between patients and healthy controls is insufficient to defend the hypothesis of frontal lobe dysfunction, as far as brain volume, resting metabolism or blood flow are concerned. The only measure, which clearly distinguishes between the patients' and controls' distributions, is the functional neuroimaging of the frontal lobe while subjects are performing an experimentally controlled task. Schizophrenic patients fail to activate their frontal cortex when the task requires it. Analysing executive abilities in relation to symptom expression leads to recognising the fact that frontal dysfunction is a characteristic of only a sub-syndrome of schizophrenia. The factor analysis of the clinical features consistently reveals three syndromes in schizophrenia, termed disorganisation, positive and negative syndromes. The substantial body of evidence that patients exhibit more than one syndrome indicates these are dimensions within a single illness rather than discrete diseases. Liddle labelled the negative syndrome as "psychomotor poverty" and associated it with malfunction of the neuronal projections from dorsal prefrontal cortex to thalamus via striatum, connections involved in the initiation of mental activity. His hypothesis was supported by the work of other, independent research groups. The patients with negative symptoms, in contrast with the nonnegative symptom group, tend to demonstrate reduced neuronal activation of the frontal cortex during executive task realisation. The nonnegative patients are indistinguishable from the healthy control subjects in this region. Neuropsychological studies reveal that severity of psychomotor poverty is associated with slowing of mental processing and deficits in tasks that require planning abilities. These frontal functions are identified with the selection, the initiation and monitoring of a wide variety of behavioural processes. It was hypothesised that executive dysfunction will appear through different patterns across symptom subtypes, but few studies sought to validate this assumption. Finally, researchers make little effort to develop theoretical conceptualisations of the aetiology of negative schizophrenic symptoms, despite the growing body of evidence on its resemblance to the dorsolateral frontal lobe syndrome. Frith proposes that defects in the initiation of spontaneous action underlie these clinical phenomena, but his definition is not specific enough to be confronted to existing literature, neither has been empirically tested. Disturbed executive functioning has detrimental impact on the quality of daily living in patients with schizophrenia. Indirect observation of the latter accounts for defective long-term adaptation, which has been correlated to severity of negative symptoms and, although not consistently, to executive deficit as assessed by neuropsychological testing. Unfortunately, this area of research lacks ecologically valid studies. Measuring executive dysfunction as it occurs in the natural setting of the patient and validating dissocialbility of frontal deficits with respect to the schizophrenic symptomatology could lead to greater individualization of treatment plans and therefore to more efficient therapy outcome.

Procedural learning in schizophrenia: further consideration on the deleterious effect of neuroleptics.

Deficits in procedural learning remain a controversial issue in schizophrenia. This may be related to the nature of the neuroleptic treatment of schizophrenic patients as conventional neuroleptics may be more deleterious than new atypical neuroleptics. However, there is no comparative study on the effect of specific neuroleptics on procedural learning. In this study, three groups of patients treated with different neuroleptics were compared to normal controls on two procedural learning tasks. In a visuo-motor task, patients and controls showed similar learning rates, although schizophrenic patients showed generally lower performances than normal controls. However, patients treated with a conventional neuroleptic, but not those treated with the atypical neuroleptics, showed many fluctuations during the initial learning phase. In a problem-solving task, all groups were comparable in performance and learning fluctuations, but learning rates were lower in patients treated with the neuroleptic showing the higher incidence of extrapyramidal symptoms. This suggests that procedural learning abilities may be significantly affected by neuroleptics in schizophrenia, although the effect may differ between tasks and the specific neuroleptics. Fluctuations in the initial learning phase of the visuo-motor task probably results from a frontal dysfunction while reduced learning rates, such as those observed in the problem solving task, may be attributed to a striatal dysfunction. This is concordant with the differential pharmacological actions of the conventional and atypical neuroleptics in these two cerebral areas.

Acute and long-term administration of anticholinergics in Parkinson's disease: specific effects on the subcortico-frontal syndrome.

Parkinson's Disease (PD) is often associated with a subcortico-frontal syndrome (SCFS) that is mainly characterized by executive dysfunctions. The complete biochemistry of these dysfunctions remain misunderstood. Most studies have focused on the well-known nigro-striatal dopaminergic degenerations of PD, but a more satisfying understanding of the SCFS has come from the study of the cholinergic systems. We present here two new experiments carried out with long-term and acute anticholinergic treatments in PD. In the first experiment, the effects of a 2-week treatment with trihexyphenidyl were compared to those observed under placebo on a neuropsychological battery. Results showed that anticholinergic-induced deficits in PD were exclusively concerned with executive functions. In the second experiment, the effects of an acute subclinical dose of scopolamine were compared between normal controls and PD patients who were devoid of cognitive deficit on a subset of executive tasks. Results indicates that PD patients but not normal controls developed a transient SCFS for the duration of the drug action. In contrast to other populations with cholinergic depletions-such as Alzheimer's disease-cholinergic blockade in PD exacerbates specifically the SCFS. Such a discrepancy between these two neuropsychological profiles are discussed in terms of the specificity of the underlying cholinergic lesions.

Attentional deficits in Parkinson's disease: partial reversibility with naphtoxazine (SDZ NVI-085), a selective noradrenergic alpha 1 agonist.

Several authors have suggested that catecholamine depletion may affect attentional processes in human subjects and could be implicated in the frontal lobe syndrome that has been described in Parkinson's disease (PD). The present study reports the effects of a placebo and naphtoxazine (SDZ-NVI-085), a selective noradrenergic alpha 1 agonist. These substances were administered to nine parkinsonian patients who were assessed on measures of attention, including neuropsychological tests and evoked potentials. The results indicate that naphtoxazine may improve performance on some tests of "frontal functions," including the Stroop and the Odd-Man-Out tests, which have been previously found to be affected in PD. However, the results of some other neuropsychological tests of frontal function were not affected by naphtoxazine. Specific evoked potentials such as the Nd1 and Nd2 curves--which are thought to reflect attentional processes and which have been found to be affected in PD--were improved by naphtoxazine. Finally, naphtoxazine reduced the percentage of errors and restored the lateralization of N100 during the Shifting Reaction Time Task, suggesting that this substance may act on the processes underlying the shifting deficit in these patients. The results are discussed in terms of the specific cognitive processes that may be affected by naphtoxazine and in terms of the role of the noradrenaline in attentional deficits found in PD.

Induction of a transient dysexecutive syndrome in Parkinson's disease using a~subclinical dose of scopolamine.

Parkinson's Disease (PD) is often associated with a subcortico-frontal syndrome (SCFS) that is mainly characterized by executive dysfunctions. The complete biochemistry of these dysfunctions remain misunderstood although many studies have suggested a role of the dopaminergic lesions. However, cholinergic lesions in this disease may also account for the SCFS occurrence. The present study has assessed the effects of an acute subclinical dose of scopolamine in normal controls and in PD patients who were devoid of cognitive deficit. Results indicates that PD patients but not normal controls developed a transient SCFS for the duration of the drug action. In contrast to other populations with cholinergic depletions - such as Alzheimer's disease - cholinergic blockage in PD exacerbates specifically the dysexecutive syndrome without inducing amnesia or sedation. Such a discrepancy between these two neuropsychological profiles are discussed in terms of the specificity of the underlying cholinergic lesions.

Sleep and quantitative EEG in patients with progressive supranuclear palsy.

Sleep architecture and quantitative EEG from wakefulness and REM sleep were studied in six patients (mean age, 70.5 years) with progressive supranuclear palsy (PSP) and compared with that of six control subjects (mean age, 69.8 years). Particular attention was given to quantifying REM sleep variables because of the known PSP-associated degeneration of the pedunculopontine tegmentum (PPT)--a critical structure in REM sleep generation. Patients with PSP had a shorter total sleep time, a lower sleep efficiency, a drastic reduction in sleep spindles, an atonic slow-wave sleep, and a lower percentage of REM sleep. The lower percentage of REM sleep was the result of both a reduction in the number of REM periods and a reduction in mean period of duration. REM density was also reduced while REM efficiency, atonia, and phasic EMG were similar to control values. REM sleep findings are consistent with the known role of the PPT in REM sleep induction. A slowing of the awake EEG was found for the six frontal leads and for C4, P4, and T4 in PSP patients. The frontal EEG slowing found in wakefulness is in accord with imaging and neuropsychological studies showing impairment of the frontal lobes in these patients. REM sleep EEG was not significantly slower in any regions. Because all previous studies on PSP have relied on visual inspection of the EEG tracings, the present finding of EEG slowing in the frontal lobes (rather than in the temporal regions or diffusely) suggests that our quantitative EEG approach may be more useful in determining specific regions of impaired cortical activity.

Differential effects of D2- and D4-blocking neuroleptics on the procedural learning of schizophrenic patients.

OBJECTIVE: To illustrate the differential effects of D2- and D4-blocking neuroleptics on the procedural learning of patients with schizophrenia. METHOD: Twenty-nine schizophrenic patients were divided into 3 groups according to their pharmacological treatment: 1) drug naive, 2) haloperidol, and 3) clozapine. They were all assessed on clinical and procedural measures, the latter being the mirror drawing task. RESULTS: All groups showed progressive learning over the successive trials, and drug-naive patients performed better than the other groups. Patients in the haloperidol group showed many fluctuations over trials, suggesting difficulty in the progressive automation of the task. Such fluctuations did not occur in the clozapine group, but performances per se were worse than in the other groups during the learning trials. Automation of the task occurred at the same point (second block of trials) for all groups. CONCLUSION: These results suggest that D2- and D4-blocking neuroleptics do not similarly affect striatal dependent procedural learning in schizophrenia.

Persistent neuropsychological deficits and vigilance impairment in sleep apnea syndrome after treatment with continuous positive airways pressure (CPAP).

The obstructive sleep apnea syndrome is characterized by nocturnal sleep disturbance, excessive daytime sleepiness and neuropsychological deficits in the areas of memory, attention, and executive tasks. In the present study, these clinical manifestations were assessed in apneic patients before and 6 months after treatment with nasally applied continuous positive airway pressure (CPAP). CPAP treatment was found to restore normal respiration during sleep and to normalize sleep organization. Daytime vigilance greatly improved with treatment but some degree of somnolence as compared to normal controls persisted. Similarly, most neuropsychological deficits normalized with treatment. The exception was for planning abilities and manual dexterity, two neuropsychological deficits that have been found to be highly correlated with the severity of nocturnal hypoxemia. These results raise the possibility that anoxic brain damage is a pathogenic factor in severe obstructive sleep apnea syndrome.

Time for reorienting of attention: a premotor hypothesis of the underlying mechanism.

The paradigm of the covert orienting of attention (COA) has shown that the displacement of visual attention may be assessed even in the absence of eye movement. Stimuli correctly cued before their presentation are usually detected faster than uncued stimuli. However, miscued stimuli induce an increased detection time, which has been attributed to the time required for the reorientation of attention from the incorrect to the correct spatial location. Currently, the mechanism of such a displacement of visual attention remains unknown. Rizzolatti et al. Neuropsychologia 25, 31-40 (1987) have suggested a premotor hypothesis which suggests that an oculomotor disprogramming and reprogramming is necessary to reorient visual attention, even if the eye movement is inhibited. Since shifting of auditory attention from one ear to the other does not require any motor control, we further investigated the model of COA in 20 normal subjects who performed two tasks requiring a reorienting of auditory attention: (1) a choice RT task that requires a response readjustment during the auditory reorienting; (2) a simple RT task that does not require a response readjustment during the auditory reorienting; (2) a simple RT task that does not require a response readjustment during the auditory reorienting. Results indicate that correctly cued stimuli significantly reduce the RT in both tasks and that this reduction is greater in the choice than in the simple RT task. This suggests that a correct cue may produce a pre-programming of the response, in addition to the pre-engagement of the perceptual attention.(ABSTRACT TRUNCATED AT 250 WORDS)

Neurobehavioral manifestations in obstructive sleep apnea syndrome before and after treatment with continuous positive airway pressure.

Obstructive sleep apnea syndrome (OSAS) is characterized by recurrent apneas during sleep, resulting in repetitive hypoxemic episodes and a constant interruption of the normal sleep pattern. Vigilance impairment and neuropsychological deficits are among the main symptoms seen in this condition. One of the major questions in this field concerns the reciprocal interactions between nocturnal hypoxemia, sleep disruption, excessive daytime sleepiness and cognitive deficits. Results of this study suggest that vigilance impairment is attributable mostly to nocturnal hypoxemia. However, in cognitive deficits, hypoxemia seems to play a major role in executive and psychomotor tasks, whereas attention and memory functions appear to be related to vigilance impairment. After treatment, hypoxemia-related deficits and some degree of sleepiness persist. These results raise the possibility of an irreversible anoxic central nervous system (CNS) damage in severe OSAS.

Obstructive sleep apnea syndrome: pathogenesis of neuropsychological deficits.

Neuropsychological deficits have been documented in patients with obstructive sleep apnea syndrome (OSAS). Both nocturnal hypoxemia and impairement of daytime vigilance have been suggested as the pathogenesis of these deficits, yet it remains difficult to find good correlations between cognitive deficits and either of these physiological parameters. In the present study, 10 normal controls were compared to 10 moderately and 10 severely apneic patients, all recorded in a sleep laboratory for two consecutive nights, with a vigilance and neuropsychological assessment made during the intervening day. Relative to the controls, moderate and severe OSAS showed differences in many cognitive functions, although the severely affected showed the greater differences. Moreover, severe apneics were also worse than moderate apneics on tests that were found to be normal in the latter group. This suggests a discontinuity in the appearance of neuropsychological deficits as OSAS progresses. Further analyses revealed that reductions in general intellectual measures, as well as in executive and psychomotor tasks were all attributable to the severity of hypoxemia, while other attention and memory deficits were related to vigiance impairment. Therefore, both vigilance impairment and nocturnal hypoxemia may differentially contribute to the cognitive dysfunctions found in OSAS.