Mapping epileptic directional brain networks using intracranial EEG data.

The human brain is a directional network system, in which brain regions are network nodes and the influence exerted by one region on another is a network edge. We refer to this directional information flow from one region to another as directional connectivity. Seizures arise from an epileptic directional network; abnormal neuronal activities start from a seizure onset zone and propagate via a network to otherwise healthy brain regions. As such, effective epilepsy diagnosis and treatment require accurate identification of directional connections among regions, i.e., mapping of epileptic patients' brain networks. This article aims to understand the epileptic brain network using intracranial electroencephalographic data-recordings of epileptic patients' brain activities in many regions. The most popular models for directional connectivity use ordinary differential equations (ODE). However, ODE models are sensitive to data noise and computationally costly. To address these issues, we propose a high-dimensional state-space multivariate autoregression (SSMAR) model for the brain's directional connectivity. Different from standard multivariate autoregression and SSMAR models, the proposed SSMAR features a cluster structure, where the brain network consists of several clusters of densely connected brain regions. We develop an expectation-maximization algorithm to estimate the proposed model and use it to map the interregional networks of epileptic patients in different seizure stages. Our method reveals the evolution of brain networks during seizure development.

Interrelationship of Sleep Disturbances and Cognitive Status on Mortality.

Sleep disturbances may promote the development and advancement of Alzheimer's disease. Our purpose was to determine if sleep disturbances were associated with earlier mortality while accounting for cognition. The National Alzheimer's Coordinating Center database was used to evaluate mortality risk conferred by sleep, and the Montreal Cognitive Assessment score determined cognitive status. Demographics, sleep disturbances, cognitive status, and comorbid/other neuropsychiatric conditions were examined as predictors of survival time via Cox regression. The sample (N = 31,110) had a median age [interquartile range] of 72 [66, 79] years, MoCA score of 23 [16, 26], and survival time of 106.0 months [104.0,108.0]; 10,278 (33%) died during follow-up; 21% (n = 6461) experienced sleep disturbances. Sleep disturbances impacted survival time depending on cognition, with the greatest effect in transition from normal to cognitive impairment (P < .001). Findings support that sleep disturbances negatively impact survival time, and the impact of sleep disturbances on survival time is interrelated with cognition.

A Review of Insomnia Treatments for Patients with Mild Cognitive Impairment.

Mild cognitive impairment (MCI) impacts approximately 20% of older adults, with many also experiencing sleep disorders, such as insomnia. Given the relationship between sleep and dementia, addressing sleep issues may offer an opportunity to treat reversible causes. There are two primary treatments for insomnia: behavioral-based (cognitive behavioral therapy for insomnia, CBT-I) and pharmacological interventions. Although CBT-I is recommended as first-line treatment for insomnia in older adults, sedative-hypnotics are more likely to be recommended than non-pharmacological treatments given their convenience and accessibility. However, there are significant concerns in prescribing medications to patients with MCI. To explore this disconnect, we reviewed insomnia treatments in older adults with MCI studies and current guidelines of pharmacological therapy. First, we reviewed studies presenting non-pharmacological treatment of insomnia in older adults with MCI. Although the search yielded over 4,000 non-duplicate titles, only one article presented data on non-pharmacological treatment of insomnia in MCI. The literature covering comorbid insomnia, CBT-I, and MCI is sparse. In contrast to review of non-pharmacological studies, studies on the pharmacological treatment of insomnia in older adults were ample. Finally, we reviewed international guidelines for pharmacological treatment of insomnia in cognitive disorders. More widely used pharmacological interventions show short-term effectiveness with problems of recurrence, ineffectiveness in inadvertent or purposeful chronic use, and adverse side effects. Despite evidence regarding adverse consequences, pharmacological treatment of insomnia remains the most common treatment for insomnia. Reflecting on age-related changes in older adults, particularly those with MCI, inappropriate or mismanagement of medication can lead to unnecessary complications. Further research examining effective behavioral-based sleep management options in older adults with cognitive impairment is needed with exploration of improved sleep on cognitive function.

Proceedings of the Sleep and Epilepsy Workshop: Section 3 Mortality: Sleep, Night, and SUDEP.

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. Likely pathophysiological mechanisms include seizure-induced cardiac and respiratory dysregulation. A frequently identified feature in SUDEP cases is that they occur at night. This raises the question of a role for sleep state in regulating of SUDEP. An association with sleep has been identified in a number of studies with patients and in animal models. The focus of this section of the Sleep and Epilepsy Workshop was on identifying and understanding the role for sleep and time of day in the pathophysiology of SUDEP.

Proceedings of the Sleep and Epilepsy Workgroup: Section 2 Comorbidities: Sleep Related Comorbidities of Epilepsy.

Epilepsy is a chronic disease with multiple, complex comorbidities. Bidirectional relationships exist among seizures, sleep, circadian rhythms, and diseases within and outside of the central nervous system. Seizures fragment sleep and can contribute to development of sleep disorders, which in turn leads to worse overall health and more seizures. Moreover, treatment options are often limited by interactions with anti-seizure medications. Advances in the fields of epilepsy and in sleep medicine have been made separately, and therefore treating patients with these comorbidities necessitates interdisciplinary approach. The focus of this section of the Sleep and Epilepsy Workgroup was to identify methods of collaboration and outline investigational, educational, and treatment priorities to mutually advance what we consider a combined field.

Effect of a Web-Based Cognitive Behavior Therapy for Insomnia Intervention With 1-Year Follow-up: A Randomized Clinical Trial.

IMPORTANCE: Although cognitive behavior therapy for insomnia (CBT-I) has been established as the first-line recommendation for the millions of adults with chronic insomnia, there is a paucity of trained clinicians to deliver this much needed treatment. Internet-delivered CBT-I has shown promise as a method to overcome this obstacle; however, the long-term effectiveness has not been proven in a representative sample with chronic insomnia. OBJECTIVE: To evaluate a web-based, automated CBT-I intervention to improve insomnia in the short term (9 weeks) and long term (1 year). DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial comparing the internet CBT-I with internet patient education at baseline, 9 weeks, 6 months, and 1 year. Altogether, 303 adults with chronic insomnia self-referred to participate, of whom 151 (49.8%) reported at least 1 medical or psychiatric comorbidity. INTERVENTIONS: The internet CBT-I (Sleep Healthy Using the Internet [SHUTi]) was a 6-week fully automated, interactive, and tailored web-based program that incorporated the primary tenets of face-to-face CBT-I. The online patient education program provided nontailored and fixed online information about insomnia. MAIN OUTCOMES AND MEASURES: The primary sleep outcomes were self-reported online ratings of insomnia severity (Insomnia Severity Index) and online sleep diary-derived values for sleep-onset latency and wake after sleep onset, collected prospectively for 10 days at each assessment period. The secondary sleep outcomes included sleep efficiency, number of awakenings, sleep quality, and total sleep time. RESULTS: Among 303 participants, the mean (SD) age was 43.28 (11.59) years, and 71.9% (218 of 303) were female. Of these, 151 were randomized to the SHUTi group and 152 to the online patient education group. Results of the 3 primary sleep outcomes showed that the overall group × time interaction was significant for all variables, favoring the SHUTi group (Insomnia Severity Index [F3,1063 = 20.65, P < .001], sleep-onset latency [F3,1042 = 6.01, P < .001], and wake after sleep onset [F3,1042 = 12.68, P < .001]). Within-group effect sizes demonstrated improvements from baseline to postassessment for the SHUTi participants (range, Cohen d = 0.79 [95% CI, 0.55-1.04] to d = 1.90 [95% CI, 1.62-2.18]). Treatment effects were maintained at the 1-year follow-up (SHUTi Insomnia Severity Index d = 2.32 [95% CI, 2.01-2.63], sleep-onset latency d = 1.41 [95% CI, 1.15-1.68], and wake after sleep onset d = 0.95 [95% CI, 0.70-1.21]), with 56.6% (69 of 122) achieving remission status and 69.7% (85 of 122) deemed treatment responders at 1 year based on Insomnia Severity Index data. All secondary sleep outcomes, except total sleep time, also showed significant overall group × time interactions, favoring the SHUTi group. CONCLUSIONS AND RELEVANCE: Given its efficacy and availability, internet-delivered CBT-I may have a key role in the dissemination of effective behavioral treatments for insomnia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01438697.