Sleep Treatments in Disorders of Consciousness: A Systematic Review

Sleep disorders are among the main comorbidities in patients with a Disorder of Consciousness (DOC). Given the key role of sleep in neural and cognitive functioning, detecting and treating sleep disorders in DOCs might be an effective therapeutic strategy to boost consciousness recovery and levels of awareness. To date, no systematic reviews have been conducted that explore the effect of sleep treatments in DOCs; thus, we systematically reviewed the existing studies on both pharmacological and non-pharmacological treatments for sleep disorders in DOCs. Among 2267 assessed articles, only 7 were included in the systematic review. The studies focused on two sleep disorder categories (sleep-related breathing disorders and circadian rhythm dysregulation) treated with both pharmacological (Modafinil and Intrathecal Baclofen) and non-pharmacological (positive airway pressure, bright light stimulation, and central thalamic deep brain stimulation) interventions. Although the limited number of studies and their heterogeneity do not allow generalized conclusions, all the studies highlighted the effectiveness of treatments on both sleep disorders and levels of awareness. For this reason, clinical and diagnostic evaluations able to detect sleep disorders in DOC patients should be adopted in the clinical routine for the purpose of intervening promptly with the most appropriate treatment.

Differential Effects of Lateral and Medial Entorhinal Cortex Lesions on Trace, Delay and Contextual Fear Memories

The entorhinal cortex (EC), with connections to the hippocampus, amygdala, and neocortex, is a critical, yet still underexplored, contributor to fear memory. Previous research suggests possible heterogeneity of function among its lateral (LEC) and medial (MEC) subregions. However, it is not well established what unique roles these subregions serve as the literature has shown mixed results depending on target of manipulation and type of conditioning used. Few studies have manipulated both the LEC and MEC within the same experiment. The present experiment systematically manipulated LEC and MEC function to examine their potential roles in fear memory expression. Long-Evans rats were trained using either trace or delay fear conditioning. The following day, rats received an N-methyl-D-aspartate (NMDA)-induced lesion to the LEC or MEC or received a sham surgery. Following recovery, rats were given an 8-min context test in the original context. The next day, rats were tested for tone freezing in a novel context with three discrete tone presentations. Further, rats were tested for hyperactivity in an open field under both dark and bright light gradient conditions. Results: Following either LEC or MEC lesion, freezing to context was significantly reduced in both trace and delay conditioned rats. LEC-lesioned rats consistently showed significantly less freezing following tone-offset (trace interval, or equivalent, and intertrial interval) in both trace and delay fear conditioned rats. Conclusions: These data suggest that the LEC may play a role in the expression of a conjunctive representation between the tone and context that mediates the maintenance of post-tone freezing.

Temporal Dynamics of Subjective and Objective Alertness During Exposure to Bright Light in the Afternoon for 5 h

Light can induce an alertness response in humans. The effects of exposure to bright light vs. dim light on the levels of alertness during the day, especially in the afternoon, as reported in the literature, are inconsistent. This study employed a multiple measurement strategy to explore the temporal variations in the effects of exposure to bright light vs. regular office light (1,200 lx vs. 200 lx at eye level, 6,500 K) on the alertness of participants for 5 h in the afternoon. In this study, 20 healthy adults (11 female; mean age 23.25 ± 2.3 years) underwent the Karolinska sleepiness scale (KSS), the auditory psychomotor vigilance test (PVT), and the waking electroencephalogram (EEG) test for two levels of light intervention. The results yielded a relatively lower relative delta power and a relatively higher beta power for the 1,200 lx condition in comparison with the 200 lx condition. However, the light conditions elicited no statistically significant differences in the KSS scores and performance with respect to the PVT. The results suggested that exposure to bright light for 5 h in the afternoon could enhance physiological arousal while exerting insignificant effects on subjective feelings and performance abilities relating to the alertness of the participants.

Association Between Evening Light Exposure and Subjective Sleep Measures Among People Living With Dementia

Excessive light exposure before bedtime can disrupt one’s circadian rhythm and can lead to poor sleep. The purpose of this study was to describe the relationship between evening light exposure and subjective sleep measures in people living with dementia (PLWD). We conducted secondary data analysis using the baseline data from Healthy Patterns Clinical Trial (N=137). We used Actiwatch Spectrum Plus to collect light data over three consecutive days. We defined evening light exposure as the average white light intensity for 4 hours before sleep. Sleep measures included Epworth Sleepiness Scale and PROMIS Sleep-Related Impairment. We used univariate regression analysis. We found that that greater evening intensity of light exposure was associated with higher daytime sleepiness (𝛽=0.209, p=0.015) and more sleep impairment (𝛽=0.228, p=0.014). The results of our study suggest that exposure to bright light during evening can disturb nighttime sleep and increase daytime sleepiness in PLWD.

Periodic wave solution of the Kundu-Mukherjee-Naskar equation in birefringent fibers via the Hamiltonian-based algorithm

The Kundu-Mukherjee-Naskar equation can be used to address certain optical soliton dynamics in the (2+1) dimensions. In this paper, we aim to find its periodic wave solution by the Hamiltonian-based algorithm. Compared with the existing results, they have a good agreement, which strongly proves the correctness of the proposed method. Finally, the numerical results are presented in the form of 3-D and 2-D plots. The results in this work are expected to shed a bright light on the study of the periodic wave solution in physics.

Bright Light Therapy for Parkinson Disease: A Literature Review and Meta-Analysis of Randomized Controlled Trials

Sleep disorders and depression are significant nonmotor symptoms (NMSs) of Parkinson disease (PD). However, few effective, evidence-proven medical treatments are available for alleviating these symptoms. Bright light therapy (BLT) is a well-established treatment for circadian rhythm sleep disorders and seasonal affective disorder. The present study conducted a literature review for the effect of BLT on PD, especially a meta-analysis of randomized controlled trials (RCTs). We searched for studies using the PubMed and Cochrane Library databases. The major outcomes were the effects on sleep and depression. The effect on motor symptoms was also analyzed as a secondary outcome. This study was registered with PROSPERO (CRD42020204454). Six studies were included in the literature review only, and the other five RCTs were included in the meta-analysis. Despite the positive effects of BLT on PD patients, which were demonstrated in noncontrolled studies, in the meta-analysis of the RCTs, BLT did not significantly improve the depressive symptoms (standardized mean difference (SMD): −0.15, 95% confidence interval (CI): −0.48 to 0.17, p = 0.36) and excessive daytime sleepiness (EDS) (SMD: −0.12, 95% CI: −0.49 to 0.25, p = 0.53) in PD patients. Regarding motor symptoms, no significant beneficial effects were conferred (SMD: −0.11, 95% CI: −0.44 to 0.21, p = 0.49). In conclusion, BLT did not significantly alleviate depression and sleepiness. The inconsistency between BLT protocols, such as the varied timing, dosages, and treatment durations, may render BLT’s efficacy difficult to demonstrate. The small effect size obtained from the present meta-analysis indicates that future RCTs are necessary, for which BLT protocols are standardized and more patients are enrolled to determine whether a significant therapeutic benefit was conferred.

No antidepressant-like acute effects of bright light on emotional information processing in healthy volunteers

Rationale Bright light treatment (BLT) is an efficacious antidepressant intervention, but its mechanism of action is not well understood. Antidepressant drugs acutely affect how emotional information is processed, pushing the brain to prioritise positive relative to negative input. Whether BLT could have a similar effect is not known to date. Objective To test whether BLT acutely influences emotional information processing similar to antidepressant drugs, using an established healthy volunteer assay. Methods Following a double-blind, parallel-group design, 49 healthy volunteers (18–65 years, 26 females) were randomly allocated to 60-min BLT (≥ 10,000 lux) or sham-placebo treatment early in the morning in autumn/winter. Immediately after treatment, emotional information processing was assessed using the Oxford Emotional Test Battery, a validated set of behavioural tasks tapping into emotional information processing in different cognitive domains. Participants also completed questionnaires before and after treatment to assess changes in subjective state. Results The BLT group did not show significantly more positively biased emotional information processing compared to the placebo group (p > 0.05 for all measures). After adjustment for pre-treatment scores, there were also no significant post-treatment differences between groups in subjective state (p > 0.05 for all measures). Conclusions BLT did not show immediate effects on emotional information processing in an established healthy volunteer assay. Thus, BLT might exert its clinical effects through a different (cognitive) mechanism than other antidepressant interventions. Future studies should corroborate this finding including clinical populations and more intensive treatment regimes, and control for potential chronobiological effects.

Out-patient triple chronotherapy for the rapid treatment and maintenance of response in depression: feasibility and pilot randomised controlled trial

Background Triple chronotherapy (sleep deprivation for 36 h, followed by 4 days of advancing the time of sleep and daily morning bright-light therapy for 6 months) has demonstrated benefits for the rapid treatment of depressive symptoms in four small controlled trials of in-patients. Aims To test the feasibility of recruitment and delivery of triple chronotherapy for out-patients with depression (ISRCTN17706836; NCT03405493). Method In a single-blind trial, 82 participants were randomised to triple chronotherapy or a control intervention. The primary outcome was the number of participants recruited per month and adherence to the protocol. Secondary outcomes included the 6-item Hamilton Rating Scale for Depression (HRSD-6) at 1 week. Timings of observer ratings were baseline and 1, 2, 4, 8 and 26 weeks after randomisation. Results The triple chronotherapy group stayed awake for the planned 36 h and 89.9% adhered to the plan of phase advance of their sleep over the following 4 days. We achieved our recruitment target (60 participants completed the trial within 13 months). There were no reported adverse side-effects. We found a significant difference between the groups by intention-to-treat analysis for the HRSD-6 at weeks 1, 8 and 26. There was a large effect size of Cohen's d = 0.8 on HRSD-6 score at week 1, increasing to d = 1.30 at week 26. A response (≥50% reduction in symptoms) was achieved by 33.3% in the triple chronotherapy group and 16.2% in the control group. This stayed relatively steady until week 26 (35.9 v. 13.9%). Conclusions Triple chronotherapy produced a significant and rapid benefit after 1 week in out-patients with depression that was sustained at 26 weeks. Cost-effectiveness trials with a larger clinical sample are required.