The caudate: a key node in the neuronal network imbalance of insomnia?

Insomnia is prevalent, severe and partially heritable. Unfortunately, its neuronal correlates remain enigmatic, hampering the development of mechanistic models and rational treatments. Consistently reported impairments concern fragmented sleep, hyper-arousal and executive dysfunction. Because fronto-striatal networks could well play a role in sleep, arousal regulation and executive functioning, the present series of studies used an executive task to evaluate fronto-striatal functioning in disturbed sleep. Patients with insomnia showed reduced recruitment of the head of the left caudate nucleus during executive functioning, which was not secondary to altered performance or baseline perfusion. Individual differences in caudate recruitment were associated with hyper-arousal severity. Seed-based functional connectivity analysis suggested that attenuated input from a projecting orbitofrontal area with reduced grey matter density contributes to altered caudate recruitment in patients with insomnia. Attenuated caudate recruitment persisted after successful treatment of insomnia, warranting evaluation as a potential vulnerability trait. A similar selective reduction in caudate recruitment could be elicited in participants without sleep complaints by slow-wave sleep fragmentation, providing a model to facilitate investigation of the causes and consequences of insomnia.

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.