Effects of Litebook EDGE™ Phototherapy on Academic Performance and Brain Activity (LiteBook)

Effects of Litebook EDGE™ Phototherapy on Academic Performance and Functional Brain Activity in Non-Depressed Adolescents

As children pass through puberty the timing of their sleep-wake cycle shifts and they experience a strong urge to stay up and awaken late. High school typically starts early in the morning and a significant percentage of normal adolescents arrive at school each day with an insufficient amount of sleep, which can take a substantial toll on their academic performance. As the primary reason for insufficient sleep is a naturally occurring propensity to stay up later in the evening it seems plausible that bright light treatment (BLT) at the appropriate time may phase advance biological clocks and potentially reverse this problem. Hence, the investigators are testing the hypothesis that consistent morning use of a light emitting diode (LED) BLT device (LiteBook Edge™) by healthy adolescents will shift the phase of their sleep wake cycle and enable them to receive an increased amount of sleep during the school week and perform better on tests of attention and academic performance and evidence signs of improved alertness. Alternatively, BLT could potentially enhance alertness through other mechanisms, such as a direct arousing effect, without exerting a discernible effect on circadian phase or sleep duration.

As children pass through puberty the timing of their sleep-wake cycle shifts and they experience a strong urge to stay up and awaken late. Hence, a large percentage of normal adolescents arrive at school each day with an insufficient amount of sleep, which can take a substantial toll on their academic performance. A growing number of human studies show that sleep promotes learning and memory. Conversely, sleep deprivation has a negative impact on cognitive and behavioral functions. Relatively few studies have examined effects of sleep deprivation on cognitive performance in adolescents. In these studies, total sleep deprivation was associated with impaired memory performance and diminished computational speed, while, partial sleep deprivation was associated with deficits in reasoning and verbal creativity. For example, male adolescents sleeping more than 8 hours per day had significantly higher reasoning ability than their peers who slept for less than 8 hours per day. Some studies reported that simpler cognitive processes such as working memory and computational speed may not be significantly affected by a single night of sleep limited to 4 to 5 hours. However, even mild sleep restriction of an hour or more, when persistent across days, can lead to memory problems as severe as seen following total sleep deprivation. The sensitivity of the adolescent brain to subtle sleep impairments was highlighted in a study where 12-14-year-olds were allowed to play stimulating computer games or watch television right before bedtime. This experience prolonged sleep latency, increased stage 2 sleep and reduced slow wave sleep. This modest degree of sleep restriction significantly impaired verbal memory consolidation Suboptimal sleep duration in adolescents was also associated with poor performance on a serial digit-learning test during morning testing sessions, but not in afternoon sessions. Between 58-68% of high school students surveyed in Ontario report that they feel "really sleepy" between 8 and 10 A.M. Thus, achievement in early morning classes may suffer the most in sleep-deprived adolescents. Fortunately, sleep only needs to be extended by a modest amount to enhance cognition in children. Sadeh showed that performance on memory, attention and vigilance tasks in children improved significantly after 1 hour of sleep extension on three consecutive nights. Gais and Backhaus have also shown the beneficial effects of sleep on memory consolidation in children and adolescents. Overall, there is compelling scientific evidence that schoolchildren, particularly adolescents, are chronically sleep deprived, that the degree of sleep restriction they experience exerts demonstrable effects on memory encoding, consolidation and processing speed, and that even a modest increase in sleep will result in measurable improvements in cognitive function. The primary reason that adolescents are sleep deprived is due to a naturally occurring phase delay in their biological clock, resulting in a propensity to stay up until late in the evening which is incompatible with the early rise times schools typically require. Light treatments at the appropriate time can phase advance the biological clock, potentially reversing this problem. The hypothesis that the investigators propose to test is that consistent morning use of the Litebook Edge™ bright light therapy device, coupled with two-hour pre-bedtime use of blue-wave light blocking glasses while watching video screens will shift the circadian phase of the sleep-wake cycle of normal adolescents. This in turn will enable them to fall asleep earlier and to receive an increased amount of sleep during the school week. Consequently, they will awaken more readily, feel more awake during early classes, and will perform better on tests of academic performance, attention and working memory. Light therapy will enhance functional connectivity of prefrontal regions involved in attention. Degree of improvement in cognition, attention and functional and structural MRI measures will be directly related to average time spent each day activating (and presumably using) the device, which will be the independent variable in the statistical analyses. This is a one-arm study, and all participants will receive active treatment. The device was designed to monitor degree of use and the primary statistical question is whether there is a significant association between degree of use and improvement in measures of wakefulness, alertness, and cognitive performance. This approach of using duration of device activation as the independent variable, in a small preliminary study, provides several advantages over a two-arm studying comparing bright white light to either placebo red light or another type of mechanical device. First, effect size measures previously calculated assumed that subjects in both groups would use the device. There will likely be significant variability between subjects in degree of use and if only a fraction of subjects assigned the bright light device used it consistently then the overall impact would be weaker and possibly missed in a two-group analysis. Using duration of device operation will enable the investigators to compare subjects who used it to a considerable degree versus subjects who hardly use it at all and would likely provide a good estimate of how much benefit accrues from different degrees of use. This is particularly important for the neuroimaging component. If the investigators compared active versus placebo devices, then only half of the neuroimaged subjects would receive the active device, which may leave the investigators comparing pre versus post effects in only 8-10 subjects. In this revised design all the neuroimaged sample (n = 16-20) would receive the active treatment making the pre-post comparisons stronger, especially when adjusted for duration of device activation. Second, using duration of device activation as the independent variable will markedly facilitate recruitment. If the investigators used a placebo device, they would need to indicate in the informed consent that subjects may receive a placebo device, without revealing what the placebo is. Instead, the investigators can now indicate in the informed consent that all subjects will receive a device that they believe is biologically active and that no placebos will be used. This also makes the protocol simpler as raters do not need to be kept blind to device type. All the investigators need to do is make sure that raters remain unaware of duration of device activation.

This is a one-arm study. Subjects will be provided with the LiteBook Edge™ (LiteBook Company LTD), which is a patented smart phone sized BLT device that provides 10,000 lux illumination at a recommended distance of 61 cm from an LED panel with peak spectral radiance in the blue color spectrum that closely corresponds to the peak spectral frequency (480 nm) of melanopsin photoreceptors that project to the suprachiasmatic nucleus and entrain the circadian clock (Hatori & Panda, 2010).

Subjects will be instructed to use the bright light treatment device, as early as possible, for 30 minutes each morning. These devices will be equipped with monitoring electronics that will enable us to download their daily degree of use. Participants will also be provided with yellow-tinted blue light blocking glasses and will be instructed to wear them starting 2 hours before bedtime if they are viewing LED or liquid-crystal display screens.

Primary outcome measure one is the degree of increase in beta EEG activity, which is indicative of wakefulness and arousal. Change in beta EEG power will be compared to degree of use of the bright light treatment device.

Primary outcome measure two is the degree of decease in theta EEG activity, which is indicative of drowsiness. Change in theta EEG power will be compared to degree of use of the bright light treatment device.

Primary outcome measure three is the change in actigraph-assessed sleep onset to an earlier hour. Change in sleep onset time will be compared to degree of use of the bright light treatment device.

Primary outcome measure four is the increase in actigraph-assessed sleep duration. Change in sleep duration will be compared to degree of use of the bright light treatment device.

Errors of omission on the Quotient ADHD System provides a measure of inattention. These errors occur when a subject fails to respond to a target stimulus. Degree of reduction in errors of omission will be compared to degree of use of the bright light treatment device.

Variability in response speed on the Quotient ADHD System to target stimuli provides another measure of inattention. Degree of reduction in response variability will be compared to degree of use of the bright light treatment device.

Participants will be tested on their ability to correctly solve as many complex math problems from high school placement exam as they can in 10 minutes. Degree of improvement will be compared to degree of use of the bright light treatment device.

Fifty single digit addition and subtraction problems will be presented to participants using the Modified Walter Reed serial addition/subtraction task to assess computational speed. Degree of improvement will be compared to degree of use of the bright light treatment device.

The volume of the dentate gyrus, a portion of the hippocampal complex in the brain will be measured using magnetic resonance imaging. This brain region is involved in memory processes and can change in size in response to stress and sleep deprivation. Increase in dentate gyrus volume will be compared to degree of use of the bright light treatment device.

Self-reported change in propensity to fall asleep in various situations will be assessed using the Epworth Sleepiness Scale. Degree of reduction in sleep propensity will be compared to degree of use of the bright light treatment.

Functional MRI imaging will be used to assess changes in the connectivity of prefrontal cortical regions during performance of a Go/No Go attention task to identify brain regions in which degree of increase in connectivity corresponds to degree of use of the bright light treatment device.

Inclusion Criteria: Enrolled in school, drowsiness/sleepiness during morning classes which interferes to some degree with academic performance but able to wake up and be on time for said classes, willingness to use a device in the morning to enhance alertness, Intelligence Quotient greater than 80 Exclusion Criteria: Symptoms of psychiatric disorder on screening, current use of medications, home schooled, involved in morning activities, like athletics, that can alter morning alertness

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