Cognitive and Behavioral Anomalies Among Insomnia Patients With Mixed Restless Legs and Periodic Limb Movement Disorder

This study examined whether patients who have periodic limb movement disorder (PLMD), with or without comorbid restless legs syndrome (RLS), display the sleep-disruptive cognitive and behavioral anomalies found among primary insomnia sufferers. Archival data from a Sleep History Questionnaire, home-based polysomnography, and a sleep log were obtained for matched RLS/PLMD, primary insomnia, and noncomplaining volunteer samples. Statistical comparisons showed that the RLS/PLMD and primary insomnia samples differed significantly from the normal sleepers in regard to their propensities for certain sleep disruptive habits, perceived difficulties controlling pre-sleep cognitive activity, and their subjective sleep appraisals. These findings suggest RLS/PLMD patients display many of the cognitive and behavioral anomalies thought to perpetuate primary insomnia. Hence, behavioral interventions may be warranted for RLS/PLMD patients.     

Cardiac variability and heart-rate increment as a marker of sleep fragmentation in patients with a sleep disorder: a preliminary study

STUDY OBJECTIVES: The ratio between the heart-rate increment to total power spectral density (%VLFI) has been introduced as a sensitive measure of sleep-related breathing disorders (SRBD). Since a complex interaction is present between sleep disorders and occurrence of arousals, we hypothesized that %VLFI and other indexes of heart-rate variability (HRV) measures reflect the degree of sleep fragmentation. METHODS: The high- and low-frequency peaks from spectral analysis (FFT) of R-R intervals, the HRV changes using wavelet transform (WT), the geometric and time domain HRV, and the %VLFI were measured in 336 sleep studies performed in patients with insomnia, SRBD and restless legs syndrome/periodic limb movement disorder (RLS/PLMD). The ability of HRV measures to assess sleep fragmentation was examined by correlation analysis and from the area under the receiver operating characteristic (ROC) curve. RESULTS: The ratio of low frequency to high frequency (LF/HF ratio) at the FFT and WT and the %VLFI were higher in patients with SRBD and RLS/PLMD, compared with patients with insomnia. These measures were related to the arousal (MA) index as well as to the apnea-hypopnea index, oxygen desaturations, and periodic leg movement index (p < .001). The presence of a sleep fragmentation defined as an MA index > 20 was well detected by the %VLFI (ROC area: 0.66 +/- 0.03) and the LF/HF ratio at WT (ROC area: 0.66 +/- 0.03). CONCLUSION: The %VLFI and LF/HF ratio provide indirect measures of sleep fragmentation, suggesting that HRV measures during sleep assess more the associated sleep fragmentation than the presence of a specific sleep disorder.     

Periodic leg movements during sleep in PLMD and RLS patients with and without pramipexole treatment

Objective

Pharmacological treatment of restless legs syndrome (RLS) patients with pramipexole (PPX) is common and evidence based, whereas the effect of pramipexole on periodic leg movements (PLM) in periodic limb movement disorder (PLMD) patients is unknown. The aim of this study was to investigate the effect of pramipexole on sleep parameters and PLM indices in RLS and in PLMD patients.

Material and methods

Retrospectively, data of two consecutive polysomnographies of 47 patients (20 women, 27 men; mean age 59.8?±?13.6 years; range 23–87 years) with RLS (n?=?29) or PLMD (n?=?18) were analyzed. Of these, 15 patients with RLS and 9 patients with PLMD were treated with 0.18 mg pramipexole directly before the second polysomnographic night.

Results

The PLMS (total PML during sleep) index of PLMD patients was significantly higher (p?=?0.007) in untreated as well in treated patients (p?=?0.007) as compared to RLS. It was significantly reduced (p?<?0.03) in both groups under PPX. In RLS + PPX as well as in PLMD + PPX, light sleep significantly increased and deep sleep significantly decreased. The parameters total sleep time (TST) and sleep efficiency showed no significant changes as compared to the first polysomnographic night.

Conclusion

Results of this retrospective study indicate that a single treatment with 0.18 mg pramipexole leads, on the one hand, to a reduction of PLM indices in sleep both in RLS and in PLMD patients but, on the other hand, to an increase of sleep stages 1 and 2 and to a decrease of deep sleep.     

Practice parameters for the treatment of restless legs syndrome and periodic limb movement disorder. An American Academy of Sleep Medicine Report. Standards of Practice Committee of the American Academy of Sleep Medicine

These are the first clinical guidelines published for the treatment of Restless Legs Syndrome (RLS) and Periodic Limb Movement Disorder (PLMD) providing evidence-based practice parameters. They were developed by the Standards of Practice Committee and reviewed and approved by the Board of Directors of the American Academy of Sleep Medicine. The guidelines provide recommendations for the practice of sleep medicine in North America regarding the treatment of RLS and PLMD. Recommendations are based on the accompanying comprehensive review of the medical literature regarding treatment of RLS and PLMD which was developed by a task force commissioned by the American Academy of Sleep Medicine. Recommendations are identified as standards, guidelines, or options, based on the strength of evidence from published studies that meet criteria for inclusion. Dopaminergic agents are the best studied and most successful agents for treatment of RLS and PLMD. Specific recommendations are also given for the use of opioid, benzodiazepine, anticonvulsant, and adrenergic medications, and for iron supplementation. In general, pharmacological treatment should be limited to individuals who meet diagnostic criteria and especially who experience insomnia and/or excessive sleepiness that is thought to occur secondary to RLS or PLMD. Individuals treated with medication should be followed by a physician and monitored for clinical response and adverse effects. It would be desirable for future investigations to employ multicenter clinical trials, with expanded numbers of subjects using double-blind, placebo-controlled designs, and an assessment of long-term response, side effects, and impact of treatment on quality of life. Evaluation of special groups such as children, pregnant women, and the elderly is warranted.     

Neurotoxic lesions at the ventral mesopontine junction change sleep time and muscle activity during sleep: an animal model of motor disorders in sleep

There is no adequate animal model of restless legs syndrome (RLS) and periodic leg movements disorder (PLMD), disorders affecting 10% of the population. Similarly, there is no model of rapid eye movement (REM) sleep behavior disorder (RBD) that explains its symptoms and its link to Parkinsonism. We previously reported that the motor inhibitory system in the brainstem extends from the medulla to the ventral mesopontine junction (VMPJ). We now examine the effects of damage to the VMPJ in the cat. Based on the lesion sites and the changes in sleep pattern and behavior, we saw three distinct syndromes resulting from such lesions; the rostrolateral, rostromedial and caudal VMPJ syndromes. The change in sleep pattern was dependent on the lesion site, but was not significantly correlated with the number of dopaminergic neurons lost. An increase in wakefulness and a decrease in slow wave sleep (SWS) and REM sleep were seen in the rostrolateral VMPJ-lesioned animals. In contrast, the sleep pattern was not significantly changed in the rostromedial and caudal VMPJ-lesioned animals. All three groups of animals showed a significant increase in periodic and isolated leg movements in SWS and increased tonic muscle activity in REM sleep. Beyond these common symptoms, an increase in phasic motor activity in REM sleep, resembling that seen in human RBD, was found in the caudal VMPJ-lesioned animals. In contrast, the increase in motor activity in SWS in rostral VMPJ-lesioned animals is similar to that seen in human RLS/PLMD patients. The proximity of the VMPJ region to the substantia nigra suggests that the link between RLS/PLMD and Parkinsonism, as well as the progression from RBD to Parkinsonism may be mediated by the spread of damage from the regions identified here into the substantia nigra.     

Periodic leg movements and restless legs syndrome

Study objectives

Periodic leg movements (PLM) are a common phenomenon in several somatic and psychiatric disorders, often related to sleep disorders. We examined the prevalence of PLM, periodic leg movement disorder (PLMD), and restless legs syndrome (RLS) in psychiatric inpatients suffering from severe sleep disturbances and tried to find possible influences of the prescribed medication.

Design, setting and patients

In a retrospective data analysis, we explored the patient’s records in 117 psychiatric inpatients, suffering from comorbidity with severe sleep disturbances.

Measurements and results

We found PLM was positive in 61.5% of our sample, while diagnosing PLMD in 25.6% and RLS in 19.7%. A total of 74% of our RLS patients suffered from PLM. Adding dopaminergic medication or reducing neuroleptic agents improved subjective sleep quality and lowered PLM indices in patients with persistent sleep disturbances. Age-related results showed high PLM scores in patients below 40 years.

Conclusions

PLM occurred in more than 60% of the study group and a PLMD was found in about 25% of our patients. We found PLM indices in our younger patients relatively high in comparison with healthy adults. However, we found no statistically significant influence of the initially prescribed medication – maybe due to polypharmacy. Goal-directed addition of dopaminergic agents or the reduction of neuroleptic drugs results in lower PLM indices and improved subjective sleep quality.     

Transverse myelitis associated with restless legs syndrome and periodic movements of sleep responsive to an oral dopaminergic agent but not to intrathecal baclofen

Periodic limb movement disorder (PLMD) and restless legs syndrome (RLS) are related sleep disorders that occur with increased frequency in spinal cord disease. Effective treatment may be obtained with dopaminergic or opioid drugs, while anticonvulsants, benzodiazepines, and possibly baclofen may be helpful. This report describes a patient who developed RLS and PLMD after acute transverse myelitis associated with infectious mononucleosis, and failed to respond to intrathecal baclofen. All symptoms of RLS/PLMD resolved after treatment with pergolide.     

Sleep loss affects vigilance: effects of chronic insomnia and sleep therapy

Although complaints of impaired daytime functioning are essential to the diagnosis of primary insomnia, objective evidence for cognitive dysfunction has been hard to establish. A prerequisite for understanding the neurocognitive consequences of primary insomnia is to establish task paradigms that robustly differentiate insomniacs from well-sleeping subjects. We hypothesized that the decline in performance that typically occurs with an increasing cognitive demand would provide a more sensitive measure than performance on a single task version. The hypothesis was tested, first, by assessing the performance on two vigilance tasks with different cognitive demands in 25 elderly patients with primary insomnia and 13 healthy well-sleeping age-matched subjects. Secondly, we investigated the performance response to sleep therapy using a waiting-list controlled design. Sleep therapy consisted of a multi-component intervention including sleep restriction, cognitive behavioral therapy, bright-light therapy, structured physical activity and body temperature manipulations. The results show that insomniacs differed markedly from controls in their reaction times across tasks with different cognitive demands: patients responded faster on the 'simple' vigilance task, yet slower on the 'complex' vigilance task. Sleep therapy effectively restored normal performance: patients became significantly slower on the 'simple' task and faster on the 'complex' task, returning to the performance levels of control subjects. These findings indicate that the performance decline associated with increasing cognitive demands is possibly the first sensitive and robust measure of the neurocognitive sequelae of insomnia. We suggest that future studies on cognition in primary insomnia should apply a design that varies task demands.     

Cognitive behavioral treatment in clinically referred chronic insomniacs: group versus individual treatment

In this study, we compared the effect of group and cognitive behavioral treatment (CBT) in clinically referred patients with chronic insomnia. The participants were 32 individually treated primary insomniacs and 74 individuals with either primary or secondary insomnia treated in a group (5-7 patients per group). The primary outcome measures were subjective sleep, quality of life (QOL), and psychological well-being. CBT produced significant changes in sleep onset latency, total sleep time, sleep efficiency, and wake after sleep onset. For total sleep time and sleep efficiency, the improvements were maintained at follow-up as well. In the questionnaires, significant improvements from treatment were seen for the Sickness Impact Profile, Sleep Evaluation Form, and Dysfunctional Beliefs and Attitudes About Sleep. All these improvements remained significant at follow-up. We conclude that CBT for insomnia is effective for both individual and group treatment. Improvements were seen in subjective sleep parameters, QOL, attitudes about sleep, and sleep evaluation in general, both posttreatment and at follow-up.     

Cognitive Behavioral Treatment in Clinically Referred Chronic Insomniacs: Group Versus Individual Treatment

In this study, we compared the effect of group and cognitive behavioral treatment (CBT) in clinically referred patients with chronic insomnia. The participants were 32 individually treated primary insomniacs and 74 individuals with either primary or secondary insomnia treated in a group (5–7 patients per group). The primary outcome measures were subjective sleep, quality of life (QOL), and psychological well-being. CBT produced significant changes in sleep onset latency, total sleep time, sleep efficiency, and wake after sleep onset. For total sleep time and sleep efficiency, the improvements were maintained at follow-up as well. In the questionnaires, significant improvements from treatment were seen for the Sickness Impact Profile, Sleep Evaluation Form, and Dysfunctional Beliefs and Attitudes About Sleep. All these improvements remained significant at follow-up. We conclude that CBT for insomnia is effective for both individual and group treatment. Improvements were seen in subjective sleep parameters, QOL, attitudes about sleep, and sleep evaluation in general, both posttreatment and at follow-up.     

Sleep education for paradoxical insomnia

This case study series investigated a new treatment for paradoxical insomnia patients as there is no standard treatment for this patient group at this time. Four paradoxical insomnia patients had a polysomnography (PSG) sleep study, an unsuccessful brief course of behavioral treatment for insomnia, and then a novel sleep education treatment comprising review of their PSG with video and exploration of the discrepancy between their reported and observed sleep experience. Two patients responded well to sleep education, mainly with improved self-reported sleep onset latency, total sleep time, and Insomnia Severity Index scores; and the other two, who exhibited sleep architecture anomalies, were unresponsive. These findings suggest that sleep education holds promise for some paradoxical insomnia patients. Suggestions for future studies are given.     

Sleepiness is not the inverse of alertness: evidence from four sleep disorder patient groups

The constructs “sleepiness” and “alertness” are often assumed to be reciprocal states of consciousness. This distinction is of increasing concern in relation to psychomotor performance tasks such as driving. We developed two separate subjective scales of alertness to complement existing sleepiness scales. Subjective sleepiness and alertness were compared in four groups of sleep-disordered patients. In a 175-patient cohort [25 narcoleptics and 50 each with sleep apnea, insomnia and periodic leg movement disorder (PLMD)], the Epworth Sleepiness Scale (ESS) was used to measure sleepiness while the Toronto Hospital Alertness Test (THAT) and ZOGIM Alertness Scale (ZOGIM-A) were used to measure alertness. Significant differences existed for sleepiness scores, with narcoleptics scoring highest on the ESS, followed by sleep apnea, with similar ESS scores for insomnia and PLMD. By contrast, alertness scores on both the THAT and ZOGIM-A did not differ significantly between the four groups. Sleepiness scores show a correlation of close to nil to alertness scores for the combined sleep disorder patient cohort, with the exception of insomnia patients, where a modest but significant inverse relationship was noted between sleepiness and alertness. Subjective states of impaired alertness and excessive sleepiness are independent constructs in the evaluation of sleep-disordered patients. The specific primary sleep disorder diagnosis may play a relevant role in mitigating this interrelationship.     

Sleep-related attentional bias in patients with primary insomnia compared with sleep experts and healthy controls

Sleep-related attentional bias has been proposed to be an important factor in the development and maintenance of primary insomnia. In this study, a newly introduced mixed modality (visual auditory) task and an emotional Stroop task were used to investigate attentional processes in patients with primary insomnia, sleep experts and healthy controls (n = 20 per group). The sleep expert group served as second control group to control for effects of frequency of concept usage (FOCU). The results of the emotional Stroop task showed a sleep-related attentional bias in the insomnia group in comparison with the expert group. However, no significant differences were detected in the other group comparisons and in the mixed modality task. The difference between insomnia patients and sleep experts in the emotional Stroop task indicates that FOCU is not the underlying process of sleep-related attentional bias. Insomnia patients seem to be more emotionally, cognitively or procedurally affected by sleep-related stimuli than sleep experts. The findings suggest that a desensitization of sleep-related stimuli might be used therapeutically, thus extending the current cognitive behavioral treatments for primary insomnia.     

认知行为疗法与佐匹克隆治疗失眠症对照研究

目的 观察认知行为疗法(CBT)和服用佐匹克隆治疗对失眠症患者的睡眠质量和心理健康水平疗效.方法 选择符合CCMD-3的失眠症患者64例,随机分为药物组、认知行为治疗组,共治疗8周,治疗前后分别测试两组的睡眠质量和心理健康水平.结果 治疗结束后,比较药物组、CBT组疗效,SCL- 90躯体化(t=2.683,P＜0...     

Symptom reports in severe chronic insomnia

STUDY OBJECTIVES: To describe patterns and severities of the daytime and nighttime symptoms of chronic insomnia patients. DESIGN: Exploratory chart review from clinicians' evaluation summaries, a self-report screening instrument, the Pittsburgh Sleep Quality Index, the Beck Depression Inventory, the Epworth Sleepiness Scale, and the Hopkins Symptom Checklist-90 (HSCL90). SETTING: A regional sleep disorders referral clinic. PATIENTS OR PARTICIPANTS: 94 patients with chronic insomnia (DSM-IV code 307.42), classified into the subgroups "Primary Insomnia," "Depression-Related," "Anxiety-Related," and "Other". INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Frequent symptoms occurred not only in nocturnal domains (e.g., sleep disturbances, environmental sensitivity), but also in daytime domains (e.g., cognitive difficulties, sleepiness). Compared to primary insomnia patients, those with depression-related insomnia endorsed more severe symptoms. All subgroups endorsed a generally similar symptom profile when single symptoms were considered in isolation. When considered conjointly, severe symptoms typical of depression and generalized social alienation had a high negative predictive value for primary insomnia. The number of severe symptoms on the HSCL90 was related to fewer sleep hours in the nonprimary insomnia subgroup but not in the primary insomnia subgroup. CONCLUSIONS: Patients with chronic insomnia report significant daytime as well as nighttime symptoms. Depression-related and primary insomnias were separable only by some highly characteristic symptoms of depression. Diagnostic subgroups of insomnia patients may vary in how their overall distress relates to diminished self-reported sleep. Nighttime and daytime symptoms need to be assessed together when measuring insomnia severity.     

Practice parameters for the psychological and behavioral treatment of insomnia: an update. An american academy of sleep medicine report

Insomnia is highly prevalent, has associated daytime consequences which impair job performance and quality of life, and is associated with increased risk of comorbidities including depression. These practice parameters provide recommendations regarding behavioral and psychological treatment approaches, which are often effective in primary and secondary insomnia. These recommendations replace or modify those published in the 1999 practice parameter paper produced by the American Sleep Disorders Association. A Task Force of content experts was appointed by the American Academy of Sleep Medicine to perform a comprehensive review of the scientific literature since 1999 and to grade the evidence regarding non-pharmacological treatments of insomnia. Recommendations were developed based on this review using evidence-based methods. These recommendations were developed by the Standards of Practice Committee and reviewed and approved by the Board of Directors of the American Academy of Sleep Medicine. Psychological and behavioral interventions are effective in the treatment of both chronic primary insomnia (Standard) and secondary insomnia (Guideline). Stimulus control therapy, relaxation training, and cognitive behavior therapy are individually effective therapies in the treatment of chronic insomnia (Standard) and sleep restriction therapy, multicomponent therapy (without cognitive therapy), biofeedback and paradoxical intention are individually effective therapies in the treatment of chronic insomnia (Guideline). There was insufficient evidence to recommend sleep hygiene education, imagery training and cognitive therapy as single therapies or when added to other specific approaches. Psychological and behavioral interventions are effective in the treatment of insomnia in older adults and in the treatment of insomnia among chronic hypnotic users (Standard).     

Psychological and behavioral treatment of insomnia:update of the recent evidence (1998-2004)

BACKGROUND: Recognition that psychological and behavioral factors play an important role in insomnia has led to increased interest in therapies targeting these factors. A review paper published in 1999 summarized the evidence regarding the efficacy of psychological and behavioral treatments for persistent insomnia. The present review provides an update of the evidence published since the original paper. As with the original paper, this review was conducted by a task force commissioned by the American Academy of Sleep Medicine in order to update its practice parameters on psychological and behavioral therapies for insomnia. METHODS: A systematic review was conducted on 37 treatment studies (N = 2246 subjects/patients) published between 1998 and 2004 inclusively and identified through Psyclnfo and Medline searches. Each study was systematically reviewed with a standard coding sheet and the following information was extracted: Study design, sample (number of participants, age, gender), diagnosis, type of treatments and controls, primary and secondary outcome measures, and main findings. Criteria for inclusion of a study were as follows: (a) the main sleep diagnosis was insomnia (primary or comorbid), (b) at least 1 treatment condition was psychological or behavioral in content, (c) the study design was a randomized controlled trial, a nonrandomized group design, a clinical case series or a single subject experimental design with a minimum of 10 subjects, and (d) the study included at least 1 of the following as dependent variables: sleep onset latency, number and/or duration of awakenings, total sleep time, sleep efficiency, or sleep quality. RESULTS: Psychological and behavioral therapies produced reliable changes in several sleep parameters of individuals with either primary insomnia or insomnia associated with medical and psychiatric disorders. Nine studies documented the benefits of insomnia treatment in older adults or for facilitating discontinuation of medication among chronic hypnotic users. Sleep improvements achieved with treatment were well sustained over time; however, with the exception of reduced psychological symptoms/ distress, there was limited evidence that improved sleep led to clinically meaningful changes in other indices of morbidity (e.g., daytime fatigue). Five treatments met criteria for empirically-supported psychological treatments for insomnia: Stimulus control therapy, relaxation, paradoxical intention, sleep restriction, and cognitive-behavior therapy. DISCUSSION: These updated findings provide additional evidence in support of the original review's conclusions as to the efficacy and generalizability of psychological and behavioral therapies for persistent insomnia. Nonetheless, further research is needed to develop therapies that would optimize outcomes and reduce morbidity, as would studies of treatment mechanisms, mediators, and moderators of outcomes. Effectiveness studies are also needed to validate those therapies when implemented in clinical settings (primary care), by non-sleep specialists. There is also a need to disseminate more effectively the available evidence in support of psychological and behavioral interventions to health-care practitioners working on the front line.     

Moderate to severe periodic limb movement disorder in childhood and adolescence.

The purpose of this study is to review clinical features of children with moderate to severe Periodic Limb Movement Disorder (PLMD). Because of our interest in both Restless Legs Syndrome (RLS) and Attention-Deficit Hyperactivity Disorder (ADHD), many of our patients had one or both of these conditions. We did a retrospective review of 129 children and adolescents who were found to have Periodic Limb Movements in Sleep (PLMS) > 5/hour of sleep. Sixty five had PLMS of 5-10/hour of sleep, 48 had PLMS of 10-25/hour of sleep and 16 had PLMS > 25/hour of sleep. One hundred and seventeen of the original 129 had ADHD. Stimulant medication did not seem to play a role in the production of PLMS. In only 25 of the 129 cases did parents note the presence of PLMS before being specifically asked to look, and even after specific instructions to look, PLMS were not noted by the parents in 39 patients. The sub-group of 16 children and adolescents--6 female, 10 male (average age 11.1 years--range 6-17 years) with moderate to severe PLMS > 25/hour of sleep are described in more detail. Fifteen of the 16 patients had ADHD. Four of the 16 had RLS and 10 of 13 patients for whom a family history was available had a parent with RLS. Two of the 16 patients had their PLMS initially misdiagnosed as seizures. Sleep disturbance was present in all 16 patients and 7 of the 16 had daytime somnolence which resolved with dopaminergic medications. To our knowledge this is the first clinical series of moderate to severe PLMS in children and adolescents to be fully described in the literature.     

CSF iron, ferritin and transferrin levels in restless legs syndrome

The aim of this study is evaluating iron, ferritin, and transferrin in both serum and CSF in patients of restless legs syndrome (RLS), based on the hypothesis that iron deficiency in the central nervous system (CNS) causes the symptoms as a result of the dysfunction of dopaminergic systems. These parameters, polysomnographic sleep measures, and subjective evaluation of the sleep quality were compared in 10 patients of idiopathic RLS (RLS group) and 10 age-matched patients of psychophysiological insomnia without RLS symptoms (non-RLS group). With sleep patterns, sleep latency was longer and sleep efficiency was lower in the RLS group than those in the non-RLS group. Periodic leg movement index in the RLS group was higher than that of the non-RLS group. With serum examination, there were no significant differences for the iron, ferritin, and transferrin values between the both groups. With CSF examination, the iron and ferritin values were lower and the transferrin values were higher in the RLS group than those in the non-RLS group. There was positive correlation between the serum and CSF ferritin levels in the both groups, but the slope of the regression lines for the RLS group was lower than that for the non-RLS group. These results indicate low brain iron concentration caused by the dysfunction of iron transportation from serum to CNS in patients with idiopathic RLS.     

Prefrontal hypoactivation and recovery in insomnia

STUDY OBJECTIVES: Although subjective complaints about daytime cognitive functioning are an essential symptom of chronic insomnia, abnormalities in functional brain activation have not previously been investigated. This study was designed to investigate functional brain activation differences as a possible result of chronic insomnia, and the reversibility of these differences after nonmedicated sleep therapy. DESIGN: Insomniacs and carefully matched controls underwent functional magnetic resonance imaging (fMRI) scanning during the performance of a category and a letter fluency task. Insomniacs were randomly assigned to either a 6-week period of nonpharmacological sleep therapy or a wait list period, after which fMRI scanning was repeated using parallel tasks. Task-related brain activation and number of generated words were considered as outcome measures. SETTING: The outpatient sleep clinic of the VU University Medical Center, Department of Clinical Neurophysiology; fMRI was performed at the Department of Radiology. PARTICIPANTS: Twenty-one patients suffering from chronic insomnia and 12 matched controls. INTERVENTIONS: Nonpharmacological sleep therapy for 6 weeks, consisting of cognitive behavioral therapy, body temperature and bright light interventions, sleep hygiene, and physical activity counseling. MEASUREMENT AND RESULTS: Compared to controls, insomnia patients showed hypoactivation of the medial and inferior prefrontal cortical areas (Brodmann Area 9, 44-45), which recovered after sleep therapy but not after a wait list period. CONCLUSIONS: Insomnia interferes in a reversible fashion with activation of the prefrontal cortical system during daytime task performance.