Timing and cortical region matter: theta power differences between teenagers affected by Major Depression and healthy controls.

In adults affected by Major Depressive Disorder (MDD), most findings point to higher electroencephalographic (EEG) theta power during wake compared to healthy controls (HC) as a potential biomarker aiding the diagnostic process or subgrouping for stratified treatment. Besides these group differences, theta power is modulated by time of day, sleep/wake history, and age. Thus, we aimed at assessing if the time of recording alters theta power in teenagers affected by MDD or HC. Standardized wake EEG power was assessed with high-density EEG in 15 children and adolescents with MDD and in 15 age- and sex-matched HC in the evening and morning. Using a two-way ANOVA, group, time, and their interaction were tested. In patients, the current severity of depression was rated using the Children's Depression Rating Scale. Broadband EEG power was lower in the morning after sleep, with a significant interaction (group x time) in central regions in the 4-6 Hz range. In MDD relative to HC, theta power was decreased over occipital areas in the evening and increased over frontal areas in the morning. A higher frontal theta power was correlated with more severe depressive mood in the morning but not in the evening. This was a cross-sectional study design, including patients on antidepressant medication. In conclusion, depending on time of recording, region-specific opposite differences of theta power were found between teenagers with MDD and HC. These findings stress the importance of the time of the recording when investigating theta power's relationship to psychopathology.

Acoustically evoked K-complexes together with sleep spindles boost verbal declarative memory consolidation in healthy adults.

Over the past decade, phase-targeted auditory stimulation (PTAS), a neuromodulation approach which presents auditory stimuli locked to the ongoing phase of slow waves during sleep, has shown potential to enhance specific aspects of sleep functions. However, the complexity of PTAS responses complicates the establishment of causality between specific electroencephalographic events and observed benefits. Here, we used down-PTAS during sleep to specifically evoke the early, K-complex (KC)-like response following PTAS without leading to a sustained increase in slow-wave activity throughout the stimulation window. Over the course of two nights, one with down-PTAS, the other without, high-density electroencephalography (hd-EEG) was recorded from 14 young healthy adults. The early response exhibited striking similarities to evoked KCs and was associated with improved verbal memory consolidation via stimulus-evoked spindle events nested into the up-phase of ongoing 1 Hz waves in a central region. These findings suggest that the early, KC-like response is sufficient to boost memory, potentially by orchestrating aspects of the hippocampal-neocortical dialogue.

Extended wakefulness alters the relationship between EEG oscillations and performance in a sustained attention task.

During drowsiness, maintaining consistent attention becomes difficult, leading to behavioural lapses. Bursts of oscillations in the electroencephalogram (EEG) might predict such lapses, given that alpha bursts increase during inattention and theta bursts increase with time spent awake. Paradoxically, however, alpha bursts decrease with time awake and theta bursts increase during focussed attention and cognitive tasks. Therefore, we investigated to what extent theta and alpha bursts predicted performance in a sustained attention task, either when well rested (baseline, BL) or following 20 h of extended wakefulness (EW). High-density EEG was measured in 18 young adults, and the timing of bursts was related to trial outcomes (fast, slow, and lapse trials). To increase the likelihood of lapses, the task was performed under soporific conditions. Against expectations, alpha bursts were more likely before fast trials and less likely before lapses at baseline, although the effect was substantially reduced during extended wakefulness. Theta bursts showed no significant relationship to behavioural outcome either at baseline or extended wakefulness. However, following exploratory analyses, we found that large-amplitude theta and alpha bursts were more likely to be followed by lapse trials during extended wakefulness but not baseline. In summary, alpha bursts during baseline anticipated better trial outcomes, whereas large-amplitude theta and alpha bursts during extended wakefulness anticipated worse outcomes. Therefore, neither theta nor alpha bursts maintain a consistent relationship with behaviour under different levels of overall vigilance.

Wake EEG oscillation dynamics reflect both sleep need and brain maturation across childhood and adolescence.

An objective measure of brain maturation is highly insightful for monitoring both typical and atypical development. Slow wave activity, recorded in the sleep electroencephalogram (EEG), reliably indexes changes in brain plasticity with age, as well as deficits related to developmental disorders such as attention-deficit hyperactivity disorder (ADHD). Unfortunately, measuring sleep EEG is resource-intensive and burdensome for participants. We therefore aimed to determine whether wake EEG could likewise index developmental changes in brain plasticity. We analyzed high-density wake EEG collected from 163 participants 3-25 years old, before and after a night of sleep. We compared two measures of oscillatory EEG activity, amplitudes and density, as well as two measures of aperiodic activity, intercepts and slopes. Furthermore, we compared these measures in patients with ADHD (8-17 y.o., N=58) to neurotypical controls. We found that wake oscillation amplitudes behaved the same as sleep slow wave activity: amplitudes decreased with age, decreased after sleep, and this overnight decrease decreased with age. Oscillation densities were also substantially age-dependent, decreasing overnight in children and increasing overnight in adolescents and adults. While both aperiodic intercepts and slopes decreased linearly with age, intercepts decreased overnight, and slopes increased overnight. Overall, our results indicate that wake oscillation amplitudes track both development and sleep need, and overnight changes in oscillation density reflect some yet-unknown shift in neural activity around puberty. No wake measure showed significant effects of ADHD, thus indicating that wake EEG measures, while easier to record, are not as sensitive as those during sleep.

How and when EEG reflects changes in neuronal connectivity due to time awake.

Being awake means forming new memories, primarily by strengthening neuronal synapses. The increase in synaptic strength results in increasing neuronal synchronicity, which should result in higher amplitude electroencephalography (EEG) oscillations. This is observed for slow waves during sleep but has not been found for wake oscillations. We hypothesized that this was due to a limitation of spectral power analysis, which does not distinguish between changes in amplitudes from changes in number of occurrences of oscillations. By using cycle-by-cycle analysis instead, we found that theta and alpha oscillation amplitudes increase as much as 30% following 24 h of extended wake. These increases were interrupted during the wake maintenance zone (WMZ), a window just before bedtime when it is difficult to fall asleep. We found that pupil diameter increased during this window, suggesting the ascending arousal system is responsible. In conclusion, wake oscillation amplitudes reflect increased synaptic strength, except during the WMZ.

The Theta Paradox: 4-8 Hz EEG Oscillations Reflect Both Sleep Pressure and Cognitive Control.

Human electroencephalographic (EEG) oscillations characterize specific behavioral and vigilance states. The frequency of these oscillations is typically sufficient to distinguish a given state; however, theta oscillations (4-8 Hz) have instead been found in near-opposite conditions of drowsiness during sleep deprivation and alert cognitive control. While the latter has been extensively studied and is often referred to as "frontal midline theta," (fmTheta) the former has been investigated far less but is considered a marker for sleep pressure during wake. In this study we investigated to what extent theta oscillations differed during cognitive tasks and sleep deprivation. We measured high-density EEG in 18 young healthy adults (nine female) performing six tasks under three levels of sleep deprivation. We found both cognitive load and sleep deprivation increased theta power in medial prefrontal cortical areas; however, sleep deprivation caused additional increases in theta in many other, predominantly frontal, areas. The sources of sleep deprivation theta (sdTheta) were task dependent, with a visual-spatial task and short-term memory (STM) task showing the most widespread effects. Notably, theta was highest in supplementary motor areas during passive music listening, and highest in the inferior temporal cortex (responsible for object recognition) during a spatial game. Furthermore, while changes in task performance were correlated with increases in theta during sleep deprivation, this relationship was not specific to the EEG of the same task and did not survive correction for multiple comparisons. Altogether, these results suggest that both during sleep deprivation and cognition theta oscillations may preferentially occur in cortical areas not involved in ongoing behavior.SIGNIFICANCE STATEMENT Electroencephalographic (EEG) research in sleep has often remained separate from research in cognition. This has led to two incompatible interpretations of the function of theta brain oscillations (4-8 Hz): that they reflect local sleep events during sleep deprivation, or that they reflect cognitive processing during tasks. With this study, we found no fundamental differences between theta oscillations during cognition and theta during sleep deprivation that would suggest different functions. Instead, our results indicate that in both cases, theta oscillations are generated by cortical areas not required for ongoing behavior. Therefore, at least in humans, theta may reflect either cortical disengagement or inhibition.

Boosting Recovery During Sleep by Means of Auditory Stimulation.

Sufficient recovery during sleep is the basis of physical and psychological well-being. Understanding the physiological mechanisms underlying this restorative function is essential for developing novel approaches to promote recovery during sleep. Phase-targeted auditory stimulation (PTAS) is an increasingly popular technique for boosting the key electrophysiological marker of recovery during sleep, slow-wave activity (SWA, 1-4 Hz EEG power). However, it is unknown whether PTAS induces physiological sleep. In this study, we demonstrate that, when applied during deep sleep, PTAS accelerates SWA decline across the night which is associated with an overnight improvement in attentional performance. Thus, we provide evidence that PTAS enhances physiological sleep and demonstrate under which conditions this occurs most efficiently. These findings will be important for future translation into clinical populations suffering from insufficient recovery during sleep.

Neuromodulation by means of phase-locked auditory stimulation affects key marker of excitability and connectivity during sleep.

The propagating pattern of sleep slow waves (high-amplitude oscillations < 4.5 Hz) serves as a blueprint of cortical excitability and brain connectivity. Phase-locked auditory stimulation is a promising tool for the modulation of ongoing brain activity during sleep; however, its underlying mechanisms remain unknown. Here, eighteen healthy young adults were measured with high-density electroencephalography in three experimental conditions; one with no stimulation, one with up- and one with down-phase stimulation; ten participants were included in the analysis. We show that up-phase auditory stimulation on a right prefrontal area locally enhances cortical involvement and promotes traveling by increasing the propagating distance and duration of targeted small-amplitude waves. On the contrary, down-phase stimulation proves more efficient at perturbing large-amplitude waves and interferes with ongoing traveling by disengaging cortical regions and interrupting high synchronicity in the target area as indicated by increased traveling speed. These results point out different underlying mechanisms mediating the effects of up- and down-phase stimulation and highlight the strength of traveling wave analysis as a sensitive and informative method for the study of connectivity and cortical excitability alterations.

Audio-tactile enhancement of cortical speech-envelope tracking.

Viewing a speaker's lip movements can improve the brain's ability to 'track' the amplitude envelope of the auditory speech signal and facilitate intelligibility. Whether such neurobehavioral benefits can also arise from tactually sensing the speech envelope on the skin is unclear. We hypothesized that tactile speech envelopes can improve neural tracking of auditory speech and thereby facilitate intelligibility. To test this, we applied continuous auditory speech and vibrotactile speech-envelope-shaped stimulation at various asynchronies to the ears and index fingers of normally-hearing human listeners while simultaneously assessing speech-recognition performance and cortical speech-envelope tracking with electroencephalography. Results indicate that tactile speech-shaped envelopes improve the cortical tracking, but not intelligibility, of degraded auditory speech. The cortical speech-tracking benefit occurs for tactile input leading the auditory input by 100 m s or less, emerges in the EEG during an early time window (~0-150 m s), and in particular involves cortical activity in the delta (1-4 Hz) range. These characteristics hint at a predictive mechanism for multisensory integration of complex slow time-varying inputs that might play a role in tactile speech communication.