Alzheimer's disease phenotypes show different sleep architecture.

INTRODUCTION: Sleep-wake disturbances are a prominent feature of Alzheimer's disease (AD). Atypical (non-amnestic) AD syndromes have different patterns of cortical vulnerability to AD. We hypothesized that atypical AD also shows differential vulnerability in subcortical nuclei that will manifest as different patterns of sleep dysfunction. METHODS: Overnight electroencephalography monitoring was performed on 48 subjects, including 15 amnestic, 19 atypical AD, and 14 controls. AD was defined based on neuropathological or biomarker confirmation. We compared sleep architecture by visual scoring and spectral power analysis in each group. RESULTS: Overall, AD cases showed increased sleep fragmentation and N1 sleep compared to controls. Compared to atypical AD groups, typical AD showed worse N3 sleep dysfunction and relatively preserved rapid eye movement (REM) sleep. DISCUSSION: Results suggest differing effects of amnestic and atypical AD variants on slow wave versus REM sleep, respectively, corroborating the hypothesis of differential selective vulnerability patterns of the subcortical nuclei within variants. Optimal symptomatic treatment for sleep dysfunction in clinical phenotypes may differ. HIGHLIGHTS: Alzheimer's disease (AD) variants show distinct patterns of sleep impairment. Amnestic/typical AD has worse N3 slow wave sleep (SWS) impairment compared to atypical AD. Atypical AD shows more rapid eye movement deficits than typical AD. Selective vulnerability patterns in subcortical areas may underlie sleep differences. Relatively preserved SWS may explain better memory scores in atypical versus typical AD.

Disentangling expectation from selective attention during perceptual decision making.

A large body of work has investigated the effects of attention and expectation on early sensory processing to support decision making. In a recent paper published in The Journal of Neuroscience, Rungratsameetaweemana et al. (Rungratsameetaweemana N, Itthipuripat S, Salazar A, Serences JT. J Neurosci 38: 5632-5648, 2018) found that expectations driven by implicitly learned task regularities do not modulate neural markers of early visual processing. Here, we discuss these findings and propose several lines of follow-up analyses and experiments that could expand on these findings in the broader perceptual decision making literature.

Brain substates induced by DMT relate to sympathetic output and meaningfulness of the experience.

N,N-Dimethyltryptamine (DMT) is a serotonergic psychedelic, known to rapidly induce short-lasting alterations in conscious experience, characterized by a profound and immersive sense of physical transcendence alongside rich and vivid auditory distortions and visual imagery. Multimodal neuroimaging data paired with dynamic analysis techniques offer a valuable approach for identifying unique signatures of brain activity - and linked autonomic physiology - naturally unfolding during the altered state of consciousness induced by DMT. We leveraged simultaneous fMRI and EKG data acquired in 14 healthy volunteers prior to, during, and after intravenous administration of DMT, and, separately, placebo. fMRI data was preprocessed to derive individual dynamic activity matrices, reflecting the similarity of brain activity in time, and community detection algorithms were applied on these matrices to identify brain activity substates; EKG data was used to derive continuous heart rate. We identified a brain substate occurring immediately after DMT injection, characterized by increased superior temporal lobe activity, and hippocampal and medial parietal deactivations under DMT. Results revealed that hippocampus and medial parietal cortex hypoactivity correlated with scores of meaningfulness of the experience. During this first post-injection substate, increased heart rate under DMT correlated negatively with the meaningfulness of the experience and positively with hippocampus/medial parietal deactivation. These results suggest a chain of influence linking sympathetic regulation to hippocampal and medial parietal deactivations under DMT, which combined, may contribute to positive mental health outcomes related to self-referential processing following psychedelic administration.

Quantifying attention span across the lifespan.

Introduction: Studies examining sustained attention abilities typically utilize metrics that quantify performance on vigilance tasks, such as response time and response time variability. However, approaches that assess the duration that an individual can maintain their attention over time are lacking. Methods: Here we developed an objective attention span metric that quantified the maximum amount of time that a participant continuously maintained an optimal "in the zone" sustained attention state while performing a continuous performance task. Results: In a population of 262 individuals aged 7-85, we showed that attention span was longer in young adults than in children and older adults. Furthermore, declines in attention span over time during task engagement were related to clinical symptoms of inattention in children. Discussion: These results suggest that quantifying attention span is a unique and meaningful method of assessing sustained attention across the lifespan and in populations with inattention symptoms.

Integrated cognitive and physical fitness training enhances attention abilities in older adults.

Preserving attention abilities is of great concern to older adults who are motivated to maintain their quality of life. Both cognitive and physical fitness interventions have been utilized in intervention studies to assess maintenance and enhancement of attention abilities in seniors, and a coupling of these approaches is a compelling strategy to buttress both cognitive and physical health in a time- and resource-effective manner. With this perspective, we created a closed-loop, motion-capture video game (Body-Brain Trainer: BBT) that adapts a player's cognitive and physical demands in an integrated approach, thus creating a personalized and cohesive experience across both domains. Older adults who engaged in two months of BBT improved on both physical fitness (measures of blood pressure and balance) and attention (behavioral and neural metrics of attention on a continuous performance task) outcome measures beyond that of an expectancy matched, active, placebo control group, with maintenance of improved attention performance evidenced 1 year later. Following training, the BBT group's improvement on the attention outcome measure exceeded performance levels attained by an untrained group of 20-year olds, and showed age-equilibration of a neural signature of attention shown to decline with age: midline frontal theta power. These findings highlight the potential benefits of an integrated, cognitive-physical, closed-loop training platform as a powerful tool for both cognitive and physical enhancement in older adults.

Reconfiguration of Electroencephalography Microstate Networks after Breath-Focused, Digital Meditation Training.

Sustained attention and working memory were improved in young adults after they engaged in a recently developed, closed-loop, digital meditation practice. Whether this type of meditation also has a sustained effect on dominant resting-state networks is currently unknown. In this study, we examined the resting brain states before and after a period of breath-focused, digital meditation training versus placebo using an electroencephalography (EEG) microstate approach. We found topographical changes in postmeditation rest, compared with baseline rest, selectively for participants who were actively involved in the meditation training and not in participants who engaged with an active, expectancy-match, placebo control paradigm. Our results suggest a reorganization of brain network connectivity after 6 weeks of intensive meditation training in brain areas, mainly including the right insula, the superior temporal gyrus, the superior parietal lobule, and the superior frontal gyrus bilaterally. These findings provide an opening for the development of a novel noninvasive treatment of neuropathological states by low-cost, breath-focused, digital meditation practice, which can be monitored by the EEG microstate approach.

Long-term maintenance of multitasking abilities following video game training in older adults.

The use of cognitive interventions to remediate deficient cognitive functions, or to enhance or preserve intact cognitive abilities, has been explored for some time, especially in older adults. However, few studies have investigated the long-term persistence of any positive benefits, with none examining whether changes in functional brain activity persist several years later. Here, we assessed whether enhanced cognitive abilities and potential underlying neural changes attained via the use of a custom-made video game (NeuroRacer) played by older adults (60-85 years old) continued to be elevated beyond control participants 6 years later. The NeuroRacer group continued to show reduced multitasking costs beyond control participants, with a neural signature of cognitive control, midline frontal theta power, also continuing to show heightened activity. However, previously evidenced performance benefits that had extended to untrained cognitive control abilities (i.e., enhanced sustained attention and working memory) did not persist, highlighting sustainability limitations. These findings continue to demonstrate the robust plasticity of the prefrontal cognitive control system in the aging brain, a potential neural mechanism underlying enhanced performance over time, and the possible long-term impact that digital therapeutics can have.

Enhancing neural markers of attention in children with ADHD using a digital therapeutic.

Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental condition characterized by diminished attentional control. Critically, these difficulties are related to negative consequences in real-life functioning both during development and into adulthood. There is now growing evidence that modulating the underlying neural circuits related to attention can improve behavior and brain function in children with ADHD. We have previously shown that game-based digital therapeutics targeting a key neural marker of attention-midline frontal theta (MFT)-yield positive effects on attentional control in several populations. However, the effects of such digital therapeutics in children with ADHD and no other comorbidities has not been yet examined. To address this gap, we assessed a sample of 25 children with ADHD (8-12 years old) on neural, behavioral, and clinical metrics of attention before and after a 4-week at-home intervention on an iPad targeting MFT circuitry. We found that children showed enhancements on a neural measure of attention (MFT power), as well as on objective behavioral measures of attention and parent reports of clinical ADHD symptoms. Importantly, we observed relationships between the neural and behavioral cognitive improvements, demonstrating that those children who showed the largest intervention-related neural gains were also those that improved the most on the behavioral tasks indexing attention. These findings provide support for using targeted, digital therapeutics to enhance multiple features of attentional control in children with ADHD. Study registration: ClinicalTrials.gov registry (NCT03844269) https://clinicaltrials.gov/ct2/show/NCT03844269.

Closed-loop digital meditation improves sustained attention in young adults.

Attention is a fundamental cognitive process that is critical for essentially all aspects of higher-order cognition and real-world activities. Younger generations have deeply embraced information technology and multitasking in their personal lives, school and the workplace, creating myriad challenges to their attention. While improving sustained attention in healthy young adults would be beneficial, enhancing this ability has proven notoriously difficult in this age group. Here we show that 6 weeks of engagement with a meditation-inspired, closed-loop software program (MediTrain) delivered on mobile devices led to gains in both sustained attention and working memory in healthy young adults. These improvements were associated with positive changes in key neural signatures of attentional control (frontal theta inter-trial coherence and parietal P3b latency), as measured by electroencephalography. Our findings suggest the utility of delivering aspects of the ancient practice of focused-attention meditation in a modern, technology-based approach and its benefits on enhancing sustained attention.