Local sleep spindle modulations in relation to specific memory cues.

Sleep spindles have been connected to memory processes in various ways. In addition, spindles appear to be modulated at the local cortical network level. We investigated whether cueing specific memories during sleep leads to localized spindle modulations in humans. During learning of word-location associations, words presented in the left and right visual hemifields were paired with different odors. By presenting a single odor during a subsequent nap, we aimed to selectively reactivate a subset of the studied material in sleeping subjects. During sleep, we observed topographically restricted spindle responses to memory cues, suggesting successful reactivation of specific memory traces. In particular, we found higher amplitude and greater incidence of fast spindles over posterior brain areas involved in visuospatial processing, contralateral to the visual field being cued. These results suggest that sleep spindles in different cortical areas reflect the reprocessing of specific memory traces.

The effect of obstructive sleep apnea and treatment with continuous positive airway pressure on stroke rehabilitation: rationale, design and methods of the TOROS study.

BACKGROUND: Obstructive sleep apnea is a common sleep disorder in stroke patients. Obstructive sleep apnea is associated with stroke severity and poor functional outcome. Continuous positive airway pressure seems to improve functional recovery in stroke rehabilitation. To date, the effect of continuous positive airway pressure on cognitive functioning in stroke patients is not well established. The current study will investigate the effectiveness of continuous positive airway pressure on both cognitive and functional outcomes in stroke patients with obstructive sleep apnea. METHODS/DESIGN: A randomized controlled trial will be conducted on the neurorehabilitation unit of Heliomare, a rehabilitation center in the Netherlands. Seventy stroke patients with obstructive sleep apnea will be randomly allocated to an intervention or control group (n = 2×35). The intervention will consist of four weeks of continuous positive airway pressure treatment. Patients allocated to the control group will receive four weeks of treatment as usual. Outcomes will be assessed at baseline, immediately after the intervention and at two-month follow-up.In a supplementary study, these 70 patients with obstructive sleep apnea will be compared to 70 stroke patients without obstructive sleep apnea with respect to cognitive and functional status at rehabilitation admission. Additionally, the societal participation of both groups will be assessed at six months and one year after inclusion. DISCUSSION: This study will provide novel information on the effects of obstructive sleep apnea and its treatment with continuous positive airway pressure on rehabilitation outcomes after stroke. TRIAL REGISTRATION NUMBER: Dutch Trial Register NTR3412.

Can a prediction model combining self-reported symptoms, sociodemographic and clinical features serve as a reliable first screening method for sleep apnea syndrome in patients with stroke?

OBJECTIVE: To determine whether a prediction model combining self-reported symptoms, sociodemographic and clinical parameters could serve as a reliable first screening method in a step-by-step diagnostic approach to sleep apnea syndrome (SAS) in stroke rehabilitation. DESIGN: Retrospective study. SETTING: Rehabilitation center. PARTICIPANTS: Consecutive sample of patients with stroke (N=620) admitted between May 2007 and July 2012. Of these, 533 patients underwent SAS screening. In total, 438 patients met the inclusion and exclusion criteria. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We administered an SAS questionnaire consisting of self-reported symptoms and sociodemographic and clinical parameters. We performed nocturnal oximetry to determine the oxygen desaturation index (ODI). We classified patients with an ODI ≥15 as having a high likelihood of SAS. We built a prediction model using backward multivariate logistic regression and evaluated diagnostic accuracy using receiver operating characteristic analysis. We calculated sensitivity, specificity, and predictive values for different probability cutoffs. RESULTS: Thirty-one percent of patients had a high likelihood of SAS. The prediction model consisted of the following variables: sex, age, body mass index, and self-reported apneas and falling asleep during daytime. The diagnostic accuracy was .76. Using a low probability cutoff (0.1), the model was very sensitive (95%) but not specific (21%). At a high cutoff (0.6), the specificity increased to 97%, but the sensitivity dropped to 24%. A cutoff of 0.3 yielded almost equal sensitivity and specificity of 72% and 69%, respectively. Depending on the cutoff, positive predictive values ranged from 35% to 75%. CONCLUSIONS: The prediction model shows acceptable diagnostic accuracy for a high likelihood of SAS. Therefore, we conclude that the prediction model can serve as a reasonable first screening method in a stepped diagnostic approach to SAS in stroke rehabilitation.

Involvement of spindles in memory consolidation is slow wave sleep-specific.

Both sleep spindles and slow oscillations have been implicated in sleep-dependent memory consolidation. Whereas spindles occur during both light and deep sleep, slow oscillations are restricted to deep sleep, raising the possibility of greater consolidation-related spindle involvement during deep sleep. We assessed declarative memory retention over an interval containing a nap and determined spindle density for light and deep sleep separately. In deep sleep, spindle density was considerably higher and showed a strong and robust positive correlation with retention. This relation was absent for light sleep, suggesting that the potentiating effects of spindles are tied to their co-occurrence with slow oscillations.

Diagnostic accuracy of nocturnal oximetry for detection of sleep apnea syndrome in stroke rehabilitation.

BACKGROUND AND PURPOSE: Sleep apnea syndrome (SAS) is a common sleep disorder in stroke patients and is associated with decreased recovery and increased risk of recurrent stroke and mortality. The standard diagnostic test for SAS is poly(somno)graphy, but this is often not feasible in stroke rehabilitation settings. This study investigated the diagnostic value of nocturnal oximetry for screening SAS in stroke rehabilitation. METHODS: Fifty-six stroke patients underwent nocturnal polygraphy and oximetry. Sensitivity, specificity, and positive and negative predictive values for the oxygen desaturation index were calculated. Patient and sleep characteristics were used to develop a predictive model of apnea-hypopnea index. RESULTS: Forty-six percent of the stroke patients had SAS. The majority of SAS patients was male, older, and had a higher body mass index than patients without SAS. Sensitivity, specificity, and positive and negative predictive values for the oxygen desaturation index ≥15 were, respectively, 77%, 100%, 100%, and 83%. Oxygen desaturation index predicted 87% of the variance in the apnea-hypopnea index. Patient characteristics did not add significantly to the prediction model. CONCLUSIONS: Nocturnal oximetry is an accurate diagnostic screening instrument for the detection of SAS in stroke patients.

Sleep spindle dynamics suggest over-consolidation in post-traumatic stress disorder.

Devastating and persisting traumatic memories are a central symptom of post-traumatic stress disorder (PTSD). Sleep problems are highly co-occurrent with PTSD and intertwined with its etiology. Notably, sleep hosts memory consolidation processes, supported by sleep spindles (11-16 Hz). Here we assess the hypothesis that intrusive memory symptoms in PTSD may arise from excessive memory consolidation, reflected in exaggerated spindling. We use a newly developed spindle detection method, entailing minimal assumptions regarding spindle phenotype, to assess spindle activity in PTSD patients and traumatized controls. Our results show increased spindle activity in PTSD, which positively correlates with daytime intrusive memory symptoms. Together, these findings provide a putative mechanism through which the profound sleep disturbance in PTSD may contribute to memory problems. Due to its uniform and unbiased approach, the new, minimal assumption spindle analysis seems a promising tool to detect aberrant spindling in psychiatric disorders.

EEG Beta Power but Not Background Music Predicts the Recall Scores in a Foreign-Vocabulary Learning Task.

As tantalizing as the idea that background music beneficially affects foreign vocabulary learning may seem, there is-partly due to a lack of theory-driven research-no consistent evidence to support this notion. We investigated inter-individual differences in the effects of background music on foreign vocabulary learning. Based on Eysenck's theory of personality we predicted that individuals with a high level of cortical arousal should perform worse when learning with background music compared to silence, whereas individuals with a low level of cortical arousal should be unaffected by background music or benefit from it. Participants were tested in a paired-associate learning paradigm consisting of three immediate word recall tasks, as well as a delayed recall task one week later. Baseline cortical arousal assessed with spontaneous EEG measurement in silence prior to the learning rounds was used for the analyses. Results revealed no interaction between cortical arousal and the learning condition (background music vs. silence). Instead, we found an unexpected main effect of cortical arousal in the beta band on recall, indicating that individuals with high beta power learned more vocabulary than those with low beta power. To substantiate this finding we conducted an exact replication of the experiment. Whereas the main effect of cortical arousal was only present in a subsample of participants, a beneficial main effect of background music appeared. A combined analysis of both experiments suggests that beta power predicts the performance in the word recall task, but that there is no effect of background music on foreign vocabulary learning. In light of these findings, we discuss whether searching for effects of background music on foreign vocabulary learning, independent of factors such as inter-individual differences and task complexity, might be a red herring. Importantly, our findings emphasize the need for sufficiently powered research designs and exact replications of theory-driven experiments when investigating effects of background music and inter-individual variation on task performance.

Effects of Continuous Positive Airway Pressure on Cognitive and Functional Outcome of Stroke Patients with Obstructive Sleep Apnea: A Randomized Controlled Trial.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) in stroke patients is associated with worse functional and cognitive status during inpatient rehabilitation. We hypothesized that a four-week period of continuous positive airway pressure (CPAP) treatment would improve cognitive and functional outcomes. METHODS: We performed a randomized controlled trial in stroke patients admitted to a neurorehabilitation unit. Patients were assigned to rehabilitation treatment as usual (control group) or to CPAP treatment (CPAP group). Primary outcomes were cognitive status measured by neuropsychological examination, and functional status measured by two neurological scales and a measure of activities of daily living (ADL). Secondary measures included sleepiness, sleep quality, fatigue, and mood. Tests were performed at baseline and after the four-week intervention period. RESULTS: We randomly assigned 20 patients to the CPAP group and 16 patients to the control group. The average CPAP compliance was 2.5 hours per night. Patients in the CPAP group showed significantly greater improvement in the cognitive domains of attention and executive functioning than the control group. CPAP compliance was associated with greater improvement in cognitive functioning. CPAP did not result in measurable improvement on measures of neurological status or ADL, or on any of the secondary measures. CONCLUSIONS: CPAP treatment improves cognitive functioning of stroke patients with OSA. COMMENTARY: A commentary on this article appears in this issue on page 467.

Effectiveness of internet-supported cognitive behavioral and chronobiological interventions and effect moderation by insomnia subtype: study protocol of a randomized controlled trial.

BACKGROUND: DSM-V criteria for insomnia disorder are met by 6 to 10% of the adult population. Insomnia has severe consequences for health and society. One of the most common treatments provided by primary caregivers is pharmacological treatment, which is far from optimal and has not been recommended since a 2005 consensus report of the National Institutes of Health. The recommended treatment is Cognitive Behavioral Therapy for Insomnia. Effectiveness, however, is still limited. Only a few studies have evaluated the effectiveness of chronobiological treatments, including the timed application of bright light, physical activity and body warming. Another opportunity for optimization of treatment is based on the idea that the people suffering from insomnia most likely represent a heterogeneous mix of subtypes, with different underlying causes and expected treatment responses. The present study aims to evaluate the possibility for optimizing insomnia treatment along the principles of personalized and stratified medicine. It evaluates the following: 1. The relative effectiveness of internet-supported cognitive behavioral therapy, bright light, physical activity and body warming; 2. Whether the effectiveness of internet-supported cognitive behavioral therapy for insomnia can be augmented by simultaneous or prior application of bright light, physical activity and body warming; and 3. Whether the effectiveness of the interventions and their combination are moderated by the insomnia subtype. METHODS/DESIGN: In a repeated measures, placebo-controlled, randomized clinical trial that included 160 people diagnosed with insomnia disorder, we are evaluating the relative effectiveness of 4 intervention weeks. Primary outcome is subjective sleep efficiency, quantified using a sleep diary. Secondary outcomes include other complaints of sleep and daytime functioning, health-related cost estimates and actigraphic objective sleep estimates. Compliance will be monitored both subjectively and objectively using activity, light and temperature sensors. Insomnia subtypes will be assessed using questionnaires. Mixed effect models will be used to evaluate intervention effects and moderation by insomnia subtype ratings. DISCUSSION: The current study addresses multiple opportunities to optimize and personalize treatment of insomnia disorder. TRIAL REGISTRATION: Netherlands National Trial Register NTR4010, 4 June 2013.

Obstructive Sleep Apnea is Related to Impaired Cognitive and Functional Status after Stroke.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a common sleep disorder in stroke patients and is associated with prolonged hospitalization, decreased functional outcome, and recurrent stroke. Research on the effect of OSA on cognitive functioning following stroke is scarce. The primary objective of this study was to compare stroke patients with and without OSA on cognitive and functional status upon admission to inpatient rehabilitation. DESIGN: Case-control study. SETTING AND PATIENTS: 147 stroke patients admitted to a neurorehabilitation unit. INTERVENTIONS: N/A. MEASUREMENTS: All patients underwent sleep examination for diagnosis of OSA. We assessed cognitive status by neuropsychological examination and functional status by two neurological scales and a measure of functional independence. RESULTS: We included 80 stroke patients with OSA and 67 stroke patients without OSA. OSA patients were older and had a higher body mass index than patients without OSA. OSA patients performed worse on tests of attention, executive functioning, visuoperception, psychomotor ability, and intelligence than those without OSA. No differences were found for vigilance, memory, and language. OSA patients had a worse neurological status, lower functional independence scores, and a longer period of hospitalization in the neurorehabilitation unit than the patients without OSA. OSA status was not associated with stroke type or classification. CONCLUSIONS: Obstructive sleep apnea (OSA) is associated with a lower cognitive and functional status in patients admitted for stroke rehabilitation. This underlines the importance of OSA as a probable prognostic factor, and calls for well-designed randomized controlled trials to study its treatability.

Neuropsychological functioning after CPAP treatment in obstructive sleep apnea: a meta-analysis.

The generally held clinical view is that treatment with continuous positive airway pressure (CPAP) improves cognition in patients with obstructive sleep apnea (OSA). However, the cognitive domains in which recovery is found differ between studies. A meta-analysis was conducted to quantify the effect of CPAP treatment in OSA on neuropsychological functioning. A literature search of studies published from January 1990 to July 2012 was performed. The inclusion criteria were: randomized controlled trial, diagnosis of OSA by poly(somno)graphy, apnea/hypopnea index, duration and compliance of CPAP treatment reported, use of one or more standardized neuropsychological tests. Mean weighted effect sizes of CPAP treatment for seven cognitive domains were calculated, including processing speed, attention, vigilance, working memory, memory, verbal fluency and visuoconstruction. Thirteen studies encompassing 554 OSA patients were included. A small, significant effect on attention was observed in favor of CPAP (d = 0.19). For the other cognitive domains the effect sizes did not reach significance. Improvement on measures of sleepiness was modest (d = 0.30-0.53) and comparable to prior research. In conclusion, this meta-analysis indicates that the effect of CPAP on cognition is small and limited to attention. Contrary to the general assumption, only slight improvement of neuropsychological functioning after CPAP treatment can be expected.

Sleeping worries away or worrying away sleep? Physiological evidence on sleep-emotion interactions.

Recent findings suggest that sleep might serve a role in emotional coping. However, most findings are based on subjective reports of sleep quality, while the relation with underlying sleep physiology is still largely unknown. In this study, the impact of an emotionally distressing experience on the EEG correlates of sleep was assessed. In addition, the association between sleep physiological parameters and the extent of emotional attenuation over sleep was determined. The experimental set up involved presentation of an emotionally neutral or distressing film fragment in the evening, followed by polysomnographic registration of undisturbed, whole-night sleep and assessment of emotional reactivity to film cues on the next evening. We found that emotional distress induced mild sleep deterioration, but also an increase in the proportion of slow wave sleep (SWS) and altered patterning of rapid eye movement (REM) sleep. Indeed, while REM sleep occurrence normally increases over the course of the night, emotional distress flattened this distribution and correlated with an increased number of REM periods. While sleep deterioration was negatively associated to emotional attenuation over sleep, the SWS response was positively related to such attenuation and may form part of a compensatory response to the stressor. Interestingly, trait-like SWS characteristics also correlated positively with the extent of emotion attenuation over sleep. The combined results provide strong evidence for an intimate reciprocal relation between sleep physiology and emotional processing. Moreover, individual differences in subjects' emotional and sleep responses suggest there may be a coupling of certain emotion and sleep traits into distinct emotional sleep types.