Cognitive enhancement (CE) is the pursuit of enhancing and increasing the core mental capacity above the normal level. With the advancement of science and technology, many different approaches to carry out enhancement are available. The use of psychostimulants as the choice of cognitive enhancer is rapidly growing. Although anecdotal and subjective evidences claim that these drugs work however, empirical evidences from studies in healthy adults show inconclusive evidences. One reason could be that these studies did not consider sleep as an important factor mediating the effect of stimulants on brain activities. My study 1 investigates the role of sleep in stimulant mediated CE. Along with sleep, there are other factors which are important when investigating the stimulants’ effect of CE such as dosage, type of cognitive tasks, individual variability and bias of stimulant drugs toward certain cognitive domain. My study 2 investigates the evidences of bias by stimulants towards specific cognitive domain/s. Stimulants are addictive and comes with many side effects that may cause long term health issues. In my study 3, I investigated CE through targeted memory reactivation (TMR) which exploits the natural process of memory formation and strengthening during sleep with sensory stimulation to manipulate the memory strength. Specifically, in study 3 I developed a homebased- TMR protocol to selectively bias the weak and strong memories. This protocol was designed to carry out the study amidst the COVID pandemic lockdown. I developed a brand-new spatial memory cognitive task for remote online participation. The TMR intervention protocol is suitable for real world and naturalist setting without the participants having to come to the lab. This new homebased-TMR protocol shows some promising results. With future improvement and refinement, it could be turned into fully automated unsupervised TMR system.

Sleep is crucial for emotional and physiological health by allowing for restorative processes to occur. Disruption of sleep, such as that caused by stress, can result in adverse health outcomes. Given the importance of stress levels and sleep for health, disparities present are troubling and have not been the focus of studies until recently. In mainly middle-age and older adult samples, ethnic minorities and those with lower socioeconomic status experience poorer sleep and higher stress. However, fewer studies with young adult samples exist. One form of stress these groups report higher incidences of is that caused by perceived judgment. Given sleep’s benefit on other forms of stress, the stress stemming from the feeling of being judged by others may also be reduced. My first two studies explore possible factors influencing sleep and stress. First, I examine whether the impact of stress on sleep is influenced by factors such as Ethnicity. Next, I explore whether environment, in the form of feelings of neighborhood safety, influences sleep and stress levels. My final study now looks at the beneficial effects of sleep with the hypothesis that sleep, through emotional regulation, can buffer the negative effects of being judged by a peer in a lab-setting.

Sleep plays a critical role in the improvement of both episodic memory and working memory, with non-rapid eye movement neural oscillations, including slow oscillations (0.5-1Hz, SO) and sleep spindles (12-15Hz), causally implicated in these processes. However, studies elucidating the precise mechanisms underlying these processes are needed. Specifically, it remains unclear how neural oscillations during sleep coordinate with functional changes in the brain to facilitate the maintenance of information-specific episodic memories, or the increases in information-general working memory.The present dissertation aims to address these gaps in knowledge by investigating the neural mechanism underlying sleep-dependent episodic memory consolidation and working memory improvement. In study 1, I investigate how sleep protects episodic memory against waking interference. I ask whether sleep protects memory against future interference or if it rescues memory after interference has already occurred. In study 2, I probe the role of sleep spindles underlying sleep-dependent episodic memory consolidation. Specifically, I present a placebo-controlled, double-blind study that pharmacologically enhances sleep spindles to establish a causal role of sleep spindles and their temporal coupling with SOs in episodic memory consolidation. In study 3, I employ simultaneous EEG-fMRI to examine the neural activities associated with working memory as well as subsequent sleep, with a specific focus on SO as it’s a shared resource for both episodic and working memory. Together, these studies lead to a theoretical model of how the same sleep event may facilitate improvements across multiple cognitive domains. Specifically, SOs and it’s temporal coupling with sleep spindles coordinate with functional changes in specific memory networks to facilitate performance.

The last decade has seen significant progress in identifying sleep mechanisms that support cognition. Most of these studies focus on the link between electrophysiological events of the central nervous system during sleep and improvements in different cognitive domains, while the dynamic shifts of the autonomic nervous system across sleep have been largely overlooked. Recent studies, however, have identified significant contributions of autonomic inputs during sleep to cognition. Yet, there remain considerable gaps in understanding how central and autonomic systems work together during sleep to facilitate cognitive improvement. My dissertation work investigates the independent and interactive roles of central and autonomic activities during sleep and wake in cognitive processing. I specifically focus on the prefrontal-subcortical working memory (WM) processing and mechanisms underlying the formation of hippocampal-dependent episodic long-term memory (LTM). Here, I first present an introduction to heart-brain interaction and memory processing during sleep. Next, I show two experimental studies where I examine the role of autonomic activities and autonomic-central couplings during sleep on WM, which has reliably been shown to benefit from sleep. Lastly, I present a pharmacological within-subjects, double-blind, placebo-controlled study that identifies separate and competing underlying mechanisms between autonomic and central activities supporting WM and LTM. In light of these three studies’ novel contributions, I propose a theoretical model – the Sleep Oscillation Switch (SOS) Model that sleep is a competitive arena in which autonomic WM and LTM vie for limited resources.

How does the human brain adapt to changes in the environment and store information to form memories? Decades of research has explored how information input from the environment triggers plastic changes in the brain, leading to new memory traces that have the potential to become long-term memories. My thesis asks what the optimal brain states (i.e., level of engagement with the external environment and the internal neural dynamics) are for these memory consolidation processes to occur. Sleep promotes memory consolidation (Rasch & Born, 2013), with the majority of prior studies focusing on the role of non-rapid eye movement (NREM) sleep for reducing forgetting in explicit memory contexts. Less is known about the role of rapid eye movement (REM) sleep, however, studies have shown REM may be critical for implicit or procedural learning (Cai, Mednick, Harrison, Kanady, & Mednick, 2009; Mednick, Nakayama, & Stickgold, 2003; Plihal & Born, 1997). The current thesis examines the effect of different brain states on memory consolidation, with a specific focus on visual perceptual learning. In the first two studies, I manipulated levels of sensory input from the external environment by using different wake conditions (active and quiet wake) compared with sleep, and manipulated internal neural dynamics by using different sleep conditions (naps with NREM sleep alone or NREM plus REM sleep). I tested perceptual learning of both motion direction (Study 1) and texture (Study 2) discrimination. My results show that REM sleep promotes training-induced improvements in performance (i.e., plasticity) on visual skills tasks. I hypothesize that REM sleep is the optimal brain state for this consolidation due to its unique combination of low external input coupled with neural dynamics that promote plasticity. As a secondary aim of this thesis, I explored the utility of napping beyond its use as an experimental tool by examining individual differences in nap-dependent learning. In other words, should everyone nap to boost daytime performance? I found that learning profiles after a nap are different in men and women (Study 1), and that people who regularly nap show greater magnitude of nap-dependent learning compared to people who nap infrequently (Study 3). These findings should be taken into consideration when recommending napping in operational settings.

The off-label use of prescription psychostimulants in healthy individuals is becoming more prevalent, particularly in college populations, prompting the new label “Generation Adderall”. Although these drugs have been shown to improve cognition in children with attention-deficit disorder (ADHD), the efficacy of stimulant medications for cognitive enhancement in healthy adults has not been definitively shown, with some research indicating positive effects on cognition, others indicating negative effects, and still others showing no effects of stimulant interventions. Further, discrepant results have been reported between, but also within cognitive domains, suggesting more research is needed to carefully illuminate and replicate these effects. I propose that one of the primary outcomes of psychostimulants, namely decreased sleep, may play an important, and as of yet, unacknowledged role in the effect of these drugs on cognition. Sleep, a basic biological need, has been shown to be important for cognitive processing, including learning, memory and attention. Remarkably, however, the interaction between stimulants, sleep and cognition in healthy adults has received little scientific attention. Here, I first present experimental evidence from two different within-subjects, crossover, double-blind, placebo-controlled studies where I examine the immediate and long-term impact of psychostimulants on two different cognitive domains; sustained attention, which has previously shown stimulant-related performance enhancement, and emotional memory, which has reliably been shown to benefit from sleep. Next, in light of these two studies’ novel contributions, I review the existing literature on stimulant cognitive enhancement and propose a theoretical model that includes sleep as the missing link in the story of psychostimulant cognitive enhancement.