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This study was designed to determine if desvenlafaxine (DV), a serotonin-norepinephrine reuptake inhibitor, can attenuate apoptosis observed in the limbic system after myocardial infarction (MI). MI was induced in rats by occlusion of the left descending artery for 40 min followed by reperfusion. Another group of sham (control) rats was similarly manipulated, but without occlusion. Half of the full cohort received DV (3 mg/kg/day intraperitoneal), starting 5 min after the onset of reperfusion; the other half received the vehicle (0.5 ml of 0.9% saline). Rats were sacrificed after 3 days for biochemical analyses and MI size measurements. Infarct size was significantly smaller in DV- compared to vehicle-treated rats. At 3 days post-MI, caspase-3 and -8 activities and terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling-positive cells were decreased in the amygdala of DV-treated rats compared to MI-vehicle controls. No difference was observed between the sham groups. The data indicates that DV given immediately after an acute MI event can reduce MI size and apoptosis in amygdala when measured three days post-MI.

Asperger's Syndrome (AS) is a pervasive developmental disorder whose continuity with High-Functioning Autism is still a matter of debate. Clinical observations suggest that patients with AS may present the same sleep disorders as autistic patients, including difficulties in initiating and maintaining sleep as well as poor dream recall. We recorded the sleep of a 25-year-old male patient with AS for two nights using a full EEG montage and compared the second night to that of a group of normal participants. We found low levels of slow wave sleep (SWS: stages 3 + 4), high levels of stage 1, and a large number of awakenings. The organization of REM sleep was unremarkable, including normal REM density. Analyses of phasic EEG events revealed a very low incidence of sleep spindles and a normal number of K-complexes over bilateral frontal and central EEG leads. In order to collect dream reports, the patient was awakened three times over two nights following at least 15 minutes of REM sleep in each case. On each occasion the patient was not aware of any mental activity happening just prior to awakening. These observations are discussed with regards to the connections that may exist between EEG sleep spindle activity, selective attention, and the capacity to generate a dream report.

La macrocefalia ha sido reportada como uno de los pocos marcadores fisiologicos de varios sindromes que se identifican durante la infancia. Sin embargo, solo un numero limitado de estudios han investigado si la macrocefalia persiste en los adultos con estas condiciones, debido a la ausencia de tablas de referencia actualizadas, construidas para el desarrollo normal de adultos. Las tablas de referencia de circunferencia cefalica disponible para adultos, no miden a los individuos mas alla de los 21 anos de edad, no estan actualizadas, y la mayoria utiliza muestras homogeneas y lo mas importante, no toman en cuenta al mismo tiempo la altura y peso del individuo. Fueron reclutados 221 hombres adultos de una comunidad urbana grande. En cada participante se midio la circunferencia cefalica, altura y peso. Se observo una relacion significativamente positiva entre la circunferencia cefalica y la altura (r = 0,379), asi como entre la circunferencia cefalica y el peso (r = 0,391), mientras la correlacion positiva fue debil con el indice de masa corporal (r = 0,213). Se proporcionan tablas para determinar el nivel de anormalidades de la circunferencia cefalica en la edad adulta, junto con una formula de calculo para la circunferencia cefalica basada en la altura y el peso. Los resultados indican la necesidad de tomar en cuenta altura y peso al momento de medir la circunferencia cefalica en adultos.

Changes in dietary omega-6/3 polyunsaturated fatty acids (PUFA) ratios affect anti- and proinflammatory equilibrium. As reperfused myocardial infarction (MI) is an inflammatory pathology that alters the cell integrity of the myocardium but also of other tissues, such as the hippocampus and amygdala, attenuation of the inflammation could be helpful in maintaining cell integrity after MI. Therefore, we hypothesized that a decrease in the dietary omega-6/3 PUFA ratio, without altering the diet content in total fat, proteins, or carbohydrates, will result in a reduction of infarct size and a diminution of postreperfusion apoptosis observed in the amygdala and hippocampus. Male Sprague–Dawley rats were fed 1 of 3 diets containing different omega-6/3 PUFA ratios for 2 weeks (5:1; 1:1; 1:5). Then, myocardial ischemia was induced by left anterior descending coronary artery occlusion for 40 min, followed by reperfusion. Cardioprotective mechanisms were studied in the myocardium at 15 min of reperfusion, along with myocardial infarct size after 24 h of reperfusion. Apoptosis was evaluated in the hippocampus and the amygdala. We found that infarct size was significantly reduced by 32% in groups 1:5 and 1:1 vs. group 5:1. Akt activity was higher in groups 1:5 and 1:1 compared with group 5:1. Caspase-3 enzymatic activity doubled in area CA1 and the dentate gyrus (DG) in group 5:1 compared with groups 1:1 and 1:5. In addition, caspase-8 enzymatic activity was increased in the DG at 24 h, and caspase-9 was enhanced in CA1 at 24 h in group 5:1 vs. groups 1:1 and 1:5. These results demonstrate that the increase in the dietary omega-3 PUFA, at the expense of omega-6 PUFA, reduces infarct size and helps to inhibit apoptosis in the limbic system after MI.

Borderline personality disorder (BPD) represents 2% of the general population, 10% of outpatient psychiatry facilities, 20% of inpatients and nearly 41% of patients seen in Emergency Room for attempted suicide. Also, 10% complete suicide and 64-66% have comorbid substance dependence. In addition, several studies report sleep subjective complaints in patients with BPD, and research has explored objective sleep disturbances.To examine the results of previous studies in polysomnography in BPD to better characterize the objective sleep disturbances in this population.A review of the literature on MedLine and PsycINFO using the term "borderline personality disorder", "sleep" and "polysomnography" allowed the review of 15 original articles on sleep assessed by PSG in subjects adults with BPD, published between 1980 and may 2010.Compared with healthy subjects, a decreased onset delay of rapid eye movements (REM) sleep and an increased REM density have been observed in BPD. In addition BPD shares with major depression the following disturbances: increase in onset latency, decreased total sleep time and efficiency.Differences between studies regarding sex, age, mood state at the time of the study and psychiatric comorbidity influence the results, which explains the disparity in findings.There are objective disturbances associated with BPD according to polysomnographic studies.

Sixteen rats were deprived of paradoxical sleep (PS) for 4 h using the “flower pot” technique and 16 other served as yoked controls. PS-deprived and control rats then had to learn a water maze using either a standard allocentric configuration (i.e., finding the submerged platform using external cues; n = 6/group) or an alternation version (goal platform alternating between two locations; n = 10/group). Rats were submitted to six trials with a cutoff time of 60 s and an intertrial interval of 5 min. Criterion was set as two consecutive successful completions. PS-deprived rats made more quadrant entries and took more time to reach criterion on the alternation task than control rats while both groups were equal on the allocentric task. Based on lesion studies (Ethier et al., this issue) we propose that tasks that require an intact medial prefrontal cortex are particularly sensitive to PS deprivation.

Acute myocardial infarction (MI) is followed, within a few hours, by neuronal loss in the central nervous system (CNS), including the limbic system, the hypothalamus, and the brainstem. Sleep before and after MI was investigated in the first experiment. In a parallel experiment, 2 weeks after MI, we quantified brainstem cholinergic neurons known to control paradoxical sleep (PS).Data were obtained from 28 adult male Sprague-Dawley rats weighing 350-375 g and maintained under a 12-12 light-dark cycle in 2 experiments on 16 and 12 rats, respectively. The 16 animals in the first experiment were implanted with chronic electroencephalographic (EEG) and electromyographic (EMG) electrodes. A week after surgery, these animals were habituated for 2 days to the recording equipment, and baseline sleep was charted for 24 h. The next morning, MI was induced in 8 rats by occluding the left anterior descending coronary artery for 40 min. The remaining 8 rats served as sham-operated controls. Sleep was recorded again 2 weeks after MI. The number of choline acetyltransferase (ChAT)-positive neurons was counted in the second, parallel experiment on 6 MI and 6 sham rats. Compared to the sham controls, MI rats displayed longer latency to sleep onset, shorter latency to paradoxical sleep (PS), and curtailed PS duration. The number of ChAT-positive neurons in the pedunculopontine tegmentum (PPT) area of MI rats was significantly decreased compared to the sham controls, while the number of laterodorsal tegmentum (LDT) cholinergic neurons was not different.Acute MI is accompanied, within 2 weeks, by PS-specific insomnia that can be explained, at least partly, by a specific loss of cholinergic neurons in an area known to control PS.

Borderline Personality Disorder (BPD) is characterized by severe instability in mood, impulse control, relationships and sleep patterns, alongside with mild cognitive disturbances in some patients. Although research on adolescent BPD has developed over the last decade, little is known about circadian sleep-wake patterns in this population. Low compliance and cooperation frequently reported in these patients impede data collection. Therefore, research had to introduce non-invasive objective measurements such as actigraphy while minimizing attrition and resurgence of suicidal ideation. This article examined the feasibility of an actigraphic study with BPD adolescents. Eighteen BPD adolescents (13-17 years old) were recruited from a specialized outpatient mood disorders clinic and asked to wear an actigraph for nine days including two weekends. Twelve (66.7%) of the 18 BPD patients who consented kept the actigraph for an average of 11.00 days (SD: 2.04), thus completing the required 9-day period. The reasons surrounding difficulties during the experiment, such as aversive emotions during interviews, dermal irritation, fragile alliance with the research assistant, are described. The factors that contributed the most to our satisfactory compliance rate included stabilized mood before inclusion, close ties between the research and the clinical teams, rapid access to an emergency psychiatric assessment if needed.

Functional interregional neural coupling was measured as EEG coherence during REM sleep, a state of endogenous cortical activation, in 9 adult autistic individuals (21.1±4.0 years) and 13 typically developed controls (21.5±4.3 years) monitored for two consecutive nights in a sleep laboratory. Spectral analysis was performed on 60 s of artefact-free EEG samples distributed equally throughout the first four REM sleep periods of the second night. EEG coherence was calculated for six frequency bands (delta, theta, alpha, sigma, beta, and total spectrum) using a 22-electrode montage. The magnitude of coherence function was computed for intra- and interhemispheric pairs of recording sites. Results were compared by Multivariate Analysis of Variance (MANOVA). Each time the autistic group showed a greater EEG coherence than the controls; it involved intrahemispheric communication among the left visual cortex (O1) and other regions either close to or distant from the occipital cortex. In contrast, lower coherence values involved frontal electrodes in the right hemisphere. No significant differences between groups were found for interhemispheric EEG coherence. These results show that the analysis of EEG coherence during REM sleep can disclose patterns of cortical connectivity that can be reduced or increased in adults with autism compared to typically developed individuals, depending of the cortical areas studied. Superior coherence involving visual perceptual areas in autism is consistent with an enhanced role of perception in autistic brain organization.

This study examined the laboratory dream content reported by 14 patients with schizophrenia and 15 controls, with a focus on reports obtained from NonREM sleep. Both the controls' and patients' frequency of dream recall following awakenings from NonREM and REM sleep were similar to values reported for healthy participants. Patients' NonREM sleep narratives were shorter than those from controls. When compared to their reports from REM sleep, both groups' NonREM sleep reports included significantly fewer words and reportable items. The controls were more likely to report a subjective feeling of bizarreness for their REM sleep reports as compared to their NonREM sleep reports. This difference was not observed in patients with schizophrenia. Taken together, these findings suggest few differences between the NonREM sleep mentation of patients with schizophrenia and of controls and that sleep stage cognitive style is comparable in both groups, with NonREM sleep reports being more thought-like, less elaborate and bizarre than REM sleep reports.

This study was designed to determine the role of tumor necrosis factor-alpha (TNFalpha) in apoptosis observed in the myocardium and limbic system after myocardial ischemia. PEG sTNFRI, a recombinant, human, soluble p55 Type 1 TNF receptor (3 mg/kg) or vehicle (saline) was administered s.c. to male Sprague-Dawley rats on days 5, 3 and 1 before myocardial ischemia. The animals were then subjected, under anesthesia, to left anterior descending coronary artery occlusion for 40 min, followed by 15-min or 72-h reperfusion. Caspase-3 and -8 activities as well as terminal dUTP nick-end labelling-positive cells were examined in the myocardium (subendocardial and subepicardial regions), lateral (LA) and medial amygdala (MA) and hippocampus (CA1, CA3, dentate gyrus (DG)). After 15 min of reperfusion, the subendocardial and CA1 regions presented an increase in caspase-3 activity, whereas caspase-8 activity appeared to be augmented in the DG. PEG sTNFRI inhibited caspase-8 activation in the DG. After 72 h of reperfusion, plasma TNFalpha levels were reduced in the treated groups. The DG, CA1, CA3 and MA showed an increment of caspase-8 activity, which was reversed by PEG sTNFRI, except in the MA. Furthermore, caspase-3 activity was increased in the CA1, DG, LA and MA. These results indicate that TNFalpha contributes to apoptosis via activation of the extrinsic pathway in the limbic system after myocardial infarction, which is not the case in the myocardium.

Actigraphy has been used in clinical pediatric populations for many years, including attention deficit-hyperactivity disorder and mood disorders to characterize circadian rhythms of motor activity, and as an alternative evaluation of sleep patterns. We present a case of an adolescent presenting with borderline personality disorder (BPD) and substance dependence for whom an investigation of sleep patterns using actigraphy and a sleep diary appeared to be useful in managing the case. Actigraphy contributed to the diagnostic clarification and disconfirmed the relevance of prescribing medication to this patient for sleep problems. Actigraphy is a cost-effective measure to evaluate sleep/wake patterns allowing for several-day-periods of observation. From the patient standpoint, actigraphy is less invasive than more in-depth investigation as polysomnography. Actigraphy might be a promising tool in those clinical occurrences when disentangling sleep disturbances from primary diagnosis or substance use is required.

The link between decrease in levels of attention and total sleep deprivation is well known but the respective contributions of slow wave sleep (SWS) and rapid eye movement sleep (REM) is still largely unknown. The aim of this study was to characterize the effects of sleep deprivation during the SWS phase (i.e., early night sleep) and the REM phase (i.e., late night sleep) on tasks that tap automatic and selective attention; these two forms of attention were indexed respectively by "mismatch negativity" (MMN) and "negative difference" (Nd) event-related potential (ERP) difference waves. Ten young adult participants were subjected to a three-night sleep protocol. They were each received one night of full sleep (F), one night of sleep deprivation during the first half of the night (H1), and one night of sleep deprivation during the second half of the night (H2). MMN and Nd were recorded the following morning of each night during two auditory oddball tasks that tapped automatic and selective attention. The effect of sleep deprivation condition was assessed using ERP amplitude measures and standardized low-resolution electromagnetic tomography method (sLORETA). ERP results revealed significant MMN amplitude reduction over frontal and temporal recording areas following the H2 night compared to F and H1, indicating reductions in levels of automatic attention. In addition, Nd amplitude over the parietal recording area was significantly increased following the H2 night compared to F and H1. sLORETA findings show significant changes from F to H2 night in frontal cortex activity, decreasing during the automatic attention task but increasing during the selective attention task. No significant change in brain activity is observed after H1 night. The restoration of attention processes is mainly achieved during REM sleep, which confirms results from previous studies in rat models. The anterior cortex seems to be more sensitive to sleep loss, while the parietal cortex acts as a compensatory resource to restore cognitive performance in a task context.

Actigraphy has been used in clinical pediatric populations for many years, including attention deficit-hyperactivity disorder and mood disorders to characterize circadian rhythms of motor activity, and as an alternative evaluation of sleep patterns. We present a case of an adolescent presenting with borderline personality disorder (BPD) and substance dependence for whom an investigation of sleep patterns using actigraphy and a sleep diary appeared to be useful in managing the case. Actigraphy contributed to the diagnostic clarification and disconfirmed the relevance of prescribing medication to this patient for sleep problems. Actigraphy is a cost-effective measure to evaluate sleep/wake patterns allowing for several-day-periods of observation. From the patient standpoint, actigraphy is less invasive than more in-depth investigation as polysomnography. Actigraphy might be a promising tool in those clinical occurrences when disentangling sleep disturbances from primary diagnosis or substance use is required.

Physical restraint applied during gestation is a commonly employed animal model of human pregnancy stress. The consequences of such a paradigm have been extensively investigated in adult male rats using a variety of physiological and behavioral measures. The behavioral repertoire of female offspring, however, has been largely ignored. The current study examines adult offspring-male and female Long Evans rats (55-90 days of age) and is a follow-up report to the consequences of maternal restraint (gestation days 10 through 19) in mother rats and their juvenile offspring. Physiological measures included weight and estrous cycle regularity. Elevated plus maze and emergence tests were used to measure anxiety, and the T-maze test, cognition. Data were analyzed via hierarchical linear modeling to account for the nesting of offspring within litters. Compared to same-sex controls, males from stressed mothers displayed a progressive attenuated weight gain over experimental weeks while females from stressed mothers maintained a stable, lower weight throughout. Twenty-five percent of females in the stressed group and none in the control group displayed irregular cycles in the first week of testing; on subsequent weeks, this group discrepancy ranged from 1% to 11%. Subtle effects were observed in anxiety measures: an interaction between sex and stress group in the analysis of head dip behavior in the elevated plus maze and decreased emergence latencies in stress groups. Results demonstrate the importance of examining the effects of maternal stress in offspring of both sexes at various developmental stages.

Monoaminergic neurotransmission is a key element in the physiopathology of depressive disorders, but information is still sparse on animal models of this disease. Here, we used the olfactory bulbectomy (OBX) model of depression to characterize cAMP-second messenger signaling pathways, i.e., adenylyl cyclase activity (basal, sodium fluoride (NaF)- and forskolin-stimulated conditions) as well as Gi and Gs protein levels in different regions of the limbic system. Two weeks after surgery and compared to sham controls, OBX rats displayed reduced NaF-stimulated adenylyl cyclase activity and increased Gi/Gs ratios in the hypothalamus, pre-frontal and cingulate cortices but not in the amygdala, hippocampus and caudate nucleus. No differences were found in basal or forskolin-stimulated conditions. The observed reduction of adenylyl cyclase activity induced by NaF and the increase in the Gi/Gs ratio could explain the changes in neurotransmission in OBX rats as well as in humans with depression.

Abstract Depression is diagnosed in 15–30% of patients following myocardial infarction (MI) and this may also be observed in the rat. We measured the effects of the antidepressant sertraline on behavioural and biochemical events following MI in a rat model. Following surgery, MI rats and sham controls were treated with sertraline (10 mg/kg, i.p.) or saline. Subgroups of rats were tested for behavioural depression 14 days after surgery. Apoptosis was estimated in other rats by measuring caspase-3 activity and TUNEL positive cells (3 days after surgery) in limbic structures (amygdale, hippocampus, hypothalamus, frontal and prefrontal cortices). Bax/Bcl-2 ratio was measured 14 days after surgery. Behavioural signs of depression (decreased sucrose intake and forced swimming time) were found in saline-treated MI rats but not in sertraline-treated rats. Compared with controls, caspase-3 activity and TUNEL positive cells were significantly increased in most limbic structures of MI rats. High prefrontal Bax/Bcl-2 ratio in MI rats correlated with low forced swimming time. Apoptosis was not found in sertraline-treated MI rats. These results establish the bases of a rat model of depression following MI and show for the first time that a selective serotonin reuptake inhibitor prevents both behavioural and biochemical markers in this model.

In both humans and animals, stress experienced during gestation is associated with physiological changes and disruptions in emotional function and cognitive ability in offspring; however, much less is known about the effects of such stress in mothers. In animal models, physical restraint is commonly employed to induce stress during gestation and results in elevated postpartum maternal anxiety and changes in maternal care. The purpose of the current study was to evaluate the consequences of restraint stress applied on gestation days 10 through 19 in mother rats and their juvenile offspring. Progeny were reared by birth mothers. Preterm anxiety was assessed in the elevated plus maze and maternal behavior in the retrieval test. Cognitive (T-maze) and anxiety measures (elevated plus maze and emergence) were applied to a subset of male and female offspring at 30-31 days of age. Weight and litter characteristics were also recorded. Mother rats exposed to stress during gestation had attenuated weight gain, elevated anxiety-like behavior, and reduced maternal care. Stressed mothers also had fewer pups and an elevated offspring mortality rate. The consequences of gestational stress in offspring were subtle and gender-dependent. Only juvenile females displayed marginal effects of gestational stress in the form of elevated anxiety-like behavior and attenuated weight gain. In the current study, although gestational stress had robust effects in the mother rat, these did not translate to similar changes in offspring behavior. The importance of focusing research on maternal responses to gestational stress is highlighted by these findings.

Apoptosis is known to occur in the limbic system after myocardial infarction (MI) in the rat. Our study was designed to evaluate the time course dynamics of this phenomenon in limbic areas. Apoptosis, i.e., caspase-3 activity and the number of terminal dUTP nick-end labelling-positive cells, as well as brain-derived neurotrophic factor (BDNF) were quantitated in sham-operated controls and MI rats 1, 2 and 7 days after surgery. Both apoptosis parameters were increased throughout, although in different structures: the CA1 region of the hippocampus and the medial amygdala at day 1, the CA1 region of the hippocampus and the lateral amygdala at day 2, and the frontal cortex at day 7. At day 2, BDNF was decreased in the prefrontal cortex and medial amygdala, whereas it was elevated in the dentate gyrus of the hippocampus; at day 7, BDNF was reduced in the frontal cortex and posterior hypothalamus but was augmented in the medial amygdala. These data indicate that post-MI apoptosis in the limbic system is a dynamic process occurring mainly in the hippocampus and amygdala during the first days after MI. The fact that BDNF was increased as early as 2 days after MI suggests that neurogenesis can occur rapidly in selected limbic regions after MI.

The pathophysiology of schizophrenia includes abnormalities in subcortical-cortical transfer of information that can be studied using REM sleep EEG spectral analysis, a measure that reflects spontaneous and endogenous thalamocortical activity. We recorded 10 patients with first-episode schizophrenia and 30 healthy controls for two consecutive nights in a sleep laboratory, using a 10-electrode EEG montage. Sixty seconds of REM sleep EEG without artifact were analyzed using FFT spectral analysis. Absolute and relative spectral amplitudes of five frequency bands (delta, theta, alpha, beta1 and beta2) were extracted and compared between the two groups. Frequency bands with significant differences were correlated with BPRS positive and negative symptoms scores. Patients with schizophrenia showed lower relative alpha and higher relative beta2 spectral amplitudes compared to healthy controls over the averaged total scalp. Analysis using cortical regions showed lower relative alpha over frontal, central and temporal regions and higher relative beta2 over the occipital region. Absolute spectral amplitude was not different between groups for any given EEG band. However, absolute alpha activity correlated negatively with BPRS positive symptoms scores and correlated positively with negative symptoms scores. Since similar results have been reported following EEG spectral analysis during the waking state, we conclude that abnormalities of subcortical-cortical transfer of information in schizophrenia could be generated by mechanisms common to REM sleep and waking.

Objectif Les troubles du sommeil chez les adolescents peuvent causer une diminution de la concentration, ainsi qu’une fatigue prolongee qui affectent negativement la performance scolaire, le comportement et la qualite de vie de ces ecoliers. L’objectif de notre etude est de determiner les habitudes et la qualite du sommeil chez les adolescents scolarises vivant en milieu rural et de detecter les facteurs qui peuvent affecter leur sommeil. Methodes Une enquete chez 556 eleves de differentes ecoles des villages du Mont-Liban a ete realisee en mai 2014 a l’aide d’un questionnaire informatise contenant 25 items base sur l’indice de la qualite du sommeil de Pittsburgh, l’indice de gravite de l’insomnie et l’echelle de somnolence de Stanford. Nous avons etudie la relation entre plusieurs facteurs lies aux habitudes du sommeil et trois variables dependantes : Insomnie initiale (difficultes d’endormissement), de maintien (reveils nocturnes) et sommeil insuffisant a l’aide d’une analyse bi-variee et une regression logistique. Resultats La majorite des adolescents interroges a rapporte des troubles d’endormissement, 52 % ont des difficultes a maintenir leur sommeil et 55,4 % ont de difficultes a se reveiller le matin. La prise de stimulants, l’usage de l’Internet ou du telephone mobile avant de se coucher et les diners tardifs semblent etre les facteurs qui predisposent a un sommeil inadequat. Ces resultats sont comparables a ceux obtenus avec les etudiants qui habitent les villes lors d’une enquete similaire menee en mai 2013. Conclusion Les adolescents interroges, habitant un village ou en ville, souffrent d’un sommeil inadequat et semblent avoir eventuellement des troubles de sommeil. Il est donc necessaire d’accroitre la sensibilisation a ce probleme dans l’education afin d’empecher son aggravation.

CPAP Use in Patients with OSAHS: In OSAHS, PROVIGIL is indicated as an adjunct to standard treatment(s) for the underlying obstruction. If continuous positive airway pressure (CPAP) is the treatment of choice for a patient, a maximal effort to treat with CPAP for an adequate period of time should be made prior to initiating PROVIGIL. If PROVIGIL is used adjunctively with CPAP, the encouragement of and periodic assessment of CPAP compliance is necessary. General: Patients should be cautioned about operating an automobile or other hazardous machinery until they are reasonably certain that PROVIGIL therapy will not adversely affect their ability to engage in such activities. Patients Using Contraceptives: The effectiveness of steroidal contraceptives may be reduced when used with PROVIGIL and for one month after discontinu- ation. Alternative or concomitant methods of contraception are recommended during and for one month after discontinuation of PROVIGIL. Cardiovascular System: In clinical studies of PROVIGIL, signs and symptoms including chest pain, palpitations, dyspnea and transient ischemic T-wave changes on ECG were observed in three subjects in association with mitral valve prolapse or left ventricular hypertrophy. It is recommended that PROVIGIL tablets not be used in patients with a history of left ventricular hypertrophy or in patients with mitral valve prolapse who have experienced the mitral valve prolapse syndrome when previously receiving CNS stimulants. Such signs may include but are not limited to ischemic ECG changes, chest pain, or arrhythmia. Patients with a recent history of MI or unstable angina should be treated with caution. Blood pressure monitoring in short-term controlled trials showed no clinically significant changes in mean systolic and diastolic blood pressure in patients receiving PROVIGIL as compared to placebo. However, a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). The differential use was slightly larger when only studies in OSAHS were included, with 3.4% of patients on PROVIGIL and 1.1% of patients on placebo requiring such alterations in the use of antihypertensive medication. Increased monitoring of blood pressure may be appropriate in patients on PROVIGIL. Central Nervous System: There have been reports of psychotic episodes associated with PROVIGIL use. One healthy male volunteer developed ideas of reference, paranoid delusions, and auditory hallucinations in association with multiple daily 600 mg doses of PROVIGIL and sleep deprivation. There was no evidence of psychosis 36 hours after drug discontinuation. Caution should be exercised when PROVIGIL is given to patients with a history of psychosis. Patients with Severe Renal Impairment: Treatment with PROVIGIL resulted in much higher exposure to its inactive metabolite, modafinil acid, but not PROVIGIL itself. Patients with Severe Hepatic Impairment: PROVIGIL should be administered at a reduced dose because its clearance is decreased. Elderly Patients: Elderly patients may have diminished renal and/or hepatic function; therefore, dosage reduction should be considered. Information for Patients: Physicians are advised to discuss the following with patients taking PROVIGIL. PROVIGIL is indicated for patients who have abnormal levels of sleepiness. PROVIGIL has been shown to improve, but not eliminate this abnormal tendency to fall asleep. Therefore, patients should not alter their previous behavior with regard to potentially dangerous activities (eg, driving, operating machinery) or other activities requiring appropriate levels of wakefulness, until and unless treatment with PROVIGIL has been shown to produce levels of wakefulness that permit such activities. Patients should be advised that PROVIGIL is not a replacement for sleep.

The present meta-analysis investigated the characteristics of sleep in patients with schizophrenia without neuroleptic treatment at the time of sleep recording. The 20 selected studies included 652 participants (321 patients with schizophrenia and 331 healthy subjects). Effect sizes were evaluated using d values for the following sleep variables: sleep latency (SL), total sleep time (TST), sleep efficiency index (SEI), total awake time (TAT), stage 2 percentage (S2%), stage 4 percentage, slow-wave-sleep percentage, rapid-eye-movement (REM) percentage, and REM latency. The initial meta-analysis revealed that patients with schizophrenia have the following sleep disorders: increased SL, decreased TST, and decreased SEI. A moderator analysis revealed that these sleep disorders were worse for the neuroleptic-withdrawal group relative to the never-treated group. However, only never-treated patients showed significantly increased TAT and diminished S2%. These results confirm that patients with schizophrenia have sleep disorders that are not necessarily a consequence of neuroleptic treatments, suggesting that sleep disorders are an intrinsic feature of schizophrenia. However, it must be noted that some sleep disorders may be amplified by residual effects of neuroleptic withdrawal, while others appear to be dampened by neuroleptic treatment.

A growing body of evidence indicates that people with autism frequently experience sleep disorders and exhibit atypical sleep architecture. In order to establish whether sleep disorders truly belong to the autism spectrum disorder (ASD) phenotype, we conducted a subjective and objective study of sleep in a group of high-functioning adults with ASD but without sleep complaints, psychiatric disorders or neurological comorbidity. We compared the subjective data of 27 ASD participants with those of 78 healthy controls matched for chronological age and gender. Subjective measures of sleep in the clinical group were compatible with insomnia and/or a tolerable phase advance of the sleep-wake cycle. Subjective data were confirmed by objective laboratory sleep recordings in a subset of 16 patients and 16 controls. Persons with autism presented with a longer sleep latency (P < 0.04), more frequent nocturnal awakenings (P < 0.03), lower sleep efficiency (P < 0.03), increased duration of stage 1 sleep (P < 0.02), decreased non-REM sleep (stages 2 + 3 + 4, P < 0.04) and slow-wave sleep (stages 3 + 4, P < 0.05), fewer stage 2 EEG sleep spindles (P < 0.004), and a lower number of rapid eye movements during REM sleep (P < 0.006) than did control participants. On clinical scales, the scores of persons with ASD on the Beck Depression Inventory were similar to those of persons without, but their trait anxiety scores on the Spielberger Anxiety Scale were higher (P < 0.02). The state anxiety scores of the Spielberger scale and cortisol levels were the same in the two groups. Objective total sleep time correlated negatively with the Social (-0.52, P < 0.05) and Communication (-0.54, P < 0.02) scales of the Autism Diagnostic Interview-Revised. The sleep of clinical subgroups (10 with high-functioning autism, six with Asperger syndrome) did not differ, except for the presence of fewer EEG sleep spindles in the Asperger syndrome subgroup (P < 0.05). In conclusion, these findings indicate that atypicalities of sleep constitute a salient feature of the adult ASD phenotype and this should be further investigated in younger patients. Moreover, the results are consistent with an atypical organization of neural networks subserving the macro- and microstructure of sleep in ASD. We are furthering this research with quantified analysis of sleep EEG.

Introduction Sleep disorders in children with autism are frequently reported on questionnaires filled by parents. The aim of this study was to characterize sleep using objective and subjective measures in the same sample of autistic children without comorbidities and no primary complaints of sleep disorders. Materials and methods Eleven autistic children (10.3 ± 2.2 years) diagnosed with ADI-R and ADOS criteria and 13 typically-developing children (10.2 ± 2.0 years) were recruited. Exclusion criteria comprised the use of psychotropic medication, a full IQ lower than 75, a history of epilepsy and spontaneous complaints of sleep disorders from the parents. After their children were recruited, parents filled a sleep diary for 2 weeks and the Child Sleep Habit Questionnaire (CSHQ); children were then recorded for 2 consecutive nights in a sleep laboratory. Sleep stages of night 2 were scored according to Rechtschaffen and Kales (1968) using 20 s. epochs. Stage 2 sleep spindles and K-complexes were visually scored on bilateral prefrontal and central electrodes; REM sleep rapid eye movements were also scored. Variables were log transformed when abnormally distributed. Groups were compared using t-tests for independent samples. Results Sleep diaries showed a longer sleep latency in autistic children (43.6 ± 39.0 mn vs. 17.2 ± 17.5 mn, p = .037). The CSHQ showed no significant group differences. Polysomnographically recorded sleep latency was longer in autistic children (33.0 ± 8.3 min vs. 14.4 ± 4.6 min, p = .023), the duration of stages 3 and 4 (slow-wave sleep: SWS) was shorter (18.2 ± 3.2% vs 23.6 ± 5.7%; p = .009) but total sleep time was similar (539.7 ± 54.3 vs. 560.8 ± 60.2; p = .94). Sleep spindle density (per hour of Stage 2) was similar in both groups at central electrodes and Fp1 but it was lower at Fp2 (119.2 ± 97.7 vs. 225.5 ± 122.2, p = .03). The density of K-complexes was lower at the four electrodes (.0001 p .01). REM sleep parameters (latency, duration, distribution, eye movement density) were not different between groups. Conclusion These results show that autistic children without subjectively reported sleep difficulties according to the CSHQ show signs of poor sleep on sleep diaries and polysomnography. Sleep diaries disclosed longer sleep latencies. Most polysomnographic differences were in nonREM sleep, raising the hypothesis of a difficulty for autistics to synchronize their cortical activity, possibly leading to impaired cortical sleep protective mechanisms such as sleep spindles and K-complexes. Acknowledgements Canadian Institute for Health Research; ”Fonds de recherche du Quebec – Sante”.

EEG recordings confirm hemispheric lateralization of brain activity during cognitive tasks. The aim of the present study was to investigate spontaneous EEG lateralization under two conditions, waking and REM sleep. Bilateral monopolar EEG was recorded in eight participants using a 12-electrode montage, before the night (5 min eyes closed) and during REM sleep. Spectral analysis (0.75-19.75 Hz) revealed left prefrontal lateralization on total spectrum amplitude power and right occipital lateralization in Delta activity during waking. In contrast, during REM sleep, right frontal lateralization in Theta and Beta activities and right lateralization in occipital Delta activity was observed. These results suggest that spontaneous EEG activities generated during waking and REM sleep are supported in part by a common thalamo-cortical neural network (right occipital Delta dominance) while additional, possibly neuro-cognitive factors modulate waking left prefrontal dominance and REM sleep right frontal dominance.

Evening and morning waking EEG (eyes closed) was recorded in 16 women and 13 men aged 18–26 years old. Participants were fitted with a 13-electrode montage (Fp1, Fp2, FZ, F7, F8, C3, C4, T3, T4, P3, P4, O1, and O2) referred to linked ears. For each recording electrode, EEG total spectral amplitude power (μV/Hz, 0.75–19.75 Hz) was compared using 2 (Gender) × 2 (Moments) analyses of variance for repeated measures and LSD post-hoc tests. We found significant simple Gender effects, with women displaying higher EEG values for Central, Frontal, Parietal, and left Temporal leads. Simple Moment effects were also found, with lower morning values in Temporal and left Frontal recording sites. A Gender × Moment interaction was found at the right Frontal recording site. No significant effects were found for Prefrontal and Occipital recording sites, whatsoever. These results bring new understandings of gender and time of day effects in waking EEG and point to different sensitivity in different cortical areas. The present results could explain some of the observations related to gender differences in cognitive performance.

We evaluated the role of the medial prefrontal cortex (mPFC) in the elaboration of egocentric navigation strategies in a water maze (WM). Lesions of mPFC cell bodies was achieved in 21 rats using bilateral injections of ibotenic acid (IA); 13 control rats were injected with saline. After 17 days, rats had to learn an allocentric (using external cues: 10 lesioned, 7 saline rats) or an egocentric WM (using internal/kinetic cues: 10 lesioned, 6 saline rats) over six trials in a same session. The initial trajectory on the sixth trial was used as an index of the elaboration of a navigation strategy. In the egocentric test, lesioned rats were more rarely located in the target quadrant than control rats. No differences were found between lesioned and control rats in the allocentric test. These results show that lesions of the mPFC impairs the capacity to elaborate an egocentric navigation strategy.

Introduction Autism is a neurodevelopemental disorder characterized by atypical connectivity between brain regions. People with autism are known to have sleep disorders and the purpose of this study was to analyze brain connectivity before and after a night of sleep using EEG coherence analysis. Materials and methods Nine adults with autism (21.1 ± 4.0 years) and 20 control participants (20.8 ± 4.2 years) were recorded for two consecutive nights in a sleep laboratory, using a 22-electrode montage. Every participant had a normal IQ and none were taking medication. Wake EEG was recorded for 5 min at bedtime and just before final rise time in the morning, while lying in bed with eyes closed. EEG coherence values were compared with a multivariate repeated measures design using Group × Moment × Frequency band factors for each electrode separately, followed by post hoc tests. Results In the evening, the autistic group displayed more Alpha coherence than controls within the left visual area (P3-O1: p = 0.049; T5-O1: p = 0.03 and T5-P3: p = 0.014). In the morning more Alpha coherence in the autistic group within the left visual area was also measured (T5-O1: p = 0.009 and T5-P3: p = 0.015) as well as more Delta coherence at the T5-O1 electrode pair (p = .027). Moreover, morning recordings showed less Delta coherence within the right frontal area, (Fp2-F8: p = 0.037; F4-F8: p = 0.011) and between left and right hemispheres (F3-F4: p = 0.019; F7-F8: p = 0.003). Conclusion A previous study performed during REM sleep (Leveille et al., 2010) found a greater intrahemispheric EEG coherence in autistic participants compared to controls between the left visual cortex and regions either close to or distant from it. The present results are in the same direction, upon both evening and morning wake recordings, suggesting that sleep per se is not responsible for these signs of overconnectivity. The present results also revealed a morning specific lower EEG coherence values for slow frequencies in the right frontal area in participants with autism compared to controls, suggesting that sleep per se could be responsible for these signs of underconnectivity. Acknowledgements Canadian Institute for Health Research; ”Fonds de recherche du Quebec – Sante”.

Introduction Studies showed that sleep spindle activity correlate with IQ scores in typically developing individuals. Sleep spindles are diminished in children and adults with autism compared to typically developing individuals. We investigated the relationship between IQ scores and sleep spindles activity in children with autism. Materials and methods Thirteen boys with high functioning autism (HFA: 10.2 ± 2.1 years old) and 13 comparison children (COM: 10.2 ± 2.0 years old) were recorded for two consecutive nights. They completed the WISC-III in the morning after night 2. The absolute number of sleep spindles and spindle index (number/hour) sigma EEG power (slow: 12–13 Hz, fast 13.25–15.75 Hz) were recorded and computed from frontal (Fp1, Fp2) and central (C3, C4) electrodes during S2 sleep. Results from the two groups were compared using Student t-tests and Mann–Whitney U- tests. Correlations between EEG measure and IQ were tested using Pearson’s rho (alpha = .05). Results There were no group differences on IQ (HFA: Global = 105.2 ± 18.7, Performance = 106.2 ± 13.0, Verbal = 103.8 ± 22.3; COM: 115.8 ± 10.3, 114.1 ± 12.1, and 115.1 ± 12.8, respectively). Spindle number and index were lower in the HFA than the COM group at Fp2 electrode (669.7 ± 467.3 and 126.8 ± 87.1 vs. 1018.8 ± 466.4 and 216.2 ± 121.2). The HFA group showed a negative correlation between C3 spindles index in the first quarter part of the night and the WISC global (r = −0.52) and verbal (C3 1/4 r = −0.62) scales. Sigma power was lower in the HFA than the COM group for C3 and C4 electrodes in the last quarter of the night (HFA: C3 = 0.925 ± 0.096, C4 = 0.650 ± 0.226; COM: C3 = 1.06 ± 0.18, C4 = 0.888 ± 0.301). The COM group showed a positive correlation between C4 fast Sigma activity in the last quarter of the night and global IQ (r = 0.592). There were no significant correlation between IQ and Sigma activity in the HFA group. Conclusion These findings indicate that the relationship between sleep EEG and IQ is different in autistic and typically developing children, both with normal IQ scores. These differences are in terms of scalp location (frontal vs. more posterior), EEG markers (spindles vs. Sigma activity) and time of night (early and late night). Acknowledgements Supported by the Canadian Institutes of Health Research and the “Fonds de la recherche du Quebec – Sante”.

Gamma-hydroxybutyrate (GHB) at low doses (5–10 mg/kg i.p.) increased and at high doses (160–320 mg/kg i.p.) decreased the spontaneous firing rate of prefrontal cortex (PFC) neurons recorded in urethane-anesthetized rats. Only excitations were blocked by NCS-382, a specific GHB receptor antagonist; this suggests that the excitatory effect of low doses of GHB is mediated by a GHB receptor whereas the inhibitory effect of high doses of GHB involves a more complex mechanism.

awakenings in every spectral frequency studied, in relation to the group and presence or absence of recall. The various spectral bands evolved according to an underlying rhythm, which is attenuated in the presence of dream recall; this was more evident in Normal subjects. Verbal activities were negatively correlated with high frequency bands in C3, T5 and P3 electrodes in controls. Conclusion: Differences between recall and no recall were detected. The spectral frequency bands powers were attenuated with dream recall. A cyclic variation in spectral power was detected in association with recall. Verbal activities correlated with high frequencies in left centro-temporoparietal areas.

The influence of the novel 5-hydroxytryptamine2 (5-HT2) receptor antagonist, RP 62203, on serotoninergic neurotransmission was investigated using an in vivo electrophysiological technique. For this purpose, the ability of RP 62203 (1-3 mg/kg i.p.) to block the inhibitory responses of prefrontal cortical neurons induced by electrical stimulation of the median raphe nucleus was examined in anesthetized rats. In addition, the effects of RP 62203 on the dopaminergic inhibitory responses induced in the prefrontal cortex by stimulation of the ventral tegmental area and on the enhancement of these responses by lysergic acid diethylamide (LSD, a 5-HT2 receptor agonist, 30 or 60 micrograms/kg i.p.), were analyzed. RP 62203 blocked the inhibition induced by median raphe nucleus stimulation in a dose-dependent and reversible fashion. In contrast, RP 62203 failed to affect the inhibitory responses induced in prefrontal cortical cells by stimulation of the ventral tegmental area. However, the enhancement by LSD of the inhibition induced by stimulation of the ventral tegmental area in the prefrontal cortex was blocked by RP 62203. These results demonstrate that RP 62203 selectively blocks serotoninergic, but not dopaminergic, neurotransmission in the prefrontal cortex.

We report here the possible effect of opiates on a patient exhibiting particularly severe restless legs syndrome (RLS) and periodic leg movements in sleep (PLMS). This patient was investigated in the sleep laboratory under three conditions, namely, unmedicated (baseline), medicated with codeine sulfate, and medicated with both codeine sulfate and pimozide. Codeine sulfate dramatically improved abnormal motor behavior in this patient. The addition of pimozide reversed the beneficial effect of codeine during the Forced Immobilization Test but not in spontaneous RLS or PLMS at night. These results are discussed in view of the possible involvement of the dopaminergic mechanism in RLS/PLMS syndrome.