Temporal association between sleep spindles and ripples in the human anterior and mediodorsal thalamus.

Sleep spindles are major oscillatory components of Non-Rapid Eye Movement (NREM) sleep, reflecting hyperpolarization-rebound sequences of thalamocortical neurons. Reports suggest a link between sleep spindles and several forms of high-frequency oscillations which are considered as expressions of pathological off-line neural plasticity in the central nervous system. Here we investigated the relationship between thalamic sleep spindles and ripples in the anterior and mediodorsal nuclei (ANT and MD) of epilepsy patients. Whole-night LFP from the ANT and MD were co-registered with scalp EEG/polysomnography by using externalized leads in 15 epilepsy patients undergoing a Deep Brain Stimulation protocol. Slow (~12 Hz) and fast (~14 Hz) sleep spindles were present in the human ANT and MD and roughly, 20% of them were associated with ripples. Ripple-associated thalamic sleep spindles were characterized by longer duration and exceeded pure spindles in terms of spindle power as indicated by time-frequency analysis. Furthermore, ripple amplitude was modulated by the phase of sleep spindles within both thalamic nuclei. No signs of pathological processes were correlated with measures of ripple and spindle association, furthermore, the density of ripple-associated sleep spindles in the ANT showed a positive correlation with verbal comprehension. Our findings indicate the involvement of the human thalamus in coalescent spindle-ripple oscillations of NREM sleep.

Nrem Slow-Wave Activity In Adolescents Is Differentially Associated With Adhd Levels And Normalized By Pharmacological Treatment.

BACKGROUND: A compelling hypothesis about ADHD etiopathogenesis is that the ADHD phenotype reflects a delay in cortical maturation. Slow-wave activity (SWA) of non-rapid eye movement (NREM) sleep electroencephalogram (EEG) is an electrophysiological index of sleep intensity reflecting cortical maturation. Available data on ADHD and SWA are conflicting and developmental differences, or the effect of pharmacological treatment are relatively unknown. METHODS: We examined, in samples (Mage=16.4, SD=1.2), of ever-medicated adolescents at-risk for ADHD (n=18, 72%boys), medication naïve adolescents at-risk for ADHD (n=15, 67%boys), and adolescents not at-risk for ADHD (n=31, 61%boys) matched for chronological age, whether controlling for non-ADHD pharmacotherapy, ADHD pharmacotherapy modulates the association between NREM SWA and ADHD risk in home sleep. RESULTS: Findings indicated medication naïve adolescents at-risk for ADHD exhibited greater first sleep cycle and entire night NREM SWA than both ever-medicated adolescents at-risk for ADHD and adolescents not at-risk for ADHD and no difference between ever-medicated, at-risk adolescents and not at-risk adolescents. CONCLUSIONS: Results support atypical cortical maturation in medication naïve adolescents at-risk for ADHD that appears to be normalized by ADHD pharmacotherapy in ever-medicated adolescents at-risk for ADHD. Greater NREM SWA may reflect a compensatory mechanism in middle-later adolescents at-risk for ADHD that normalizes an earlier occurring developmental delay.

Theta and alpha activity are differentially associated with physiological and rating scale measures of affective processing in adolescents with but not without ADHD.

Although atypical theta and alpha activity may be biomarkers of attention-deficit/hyperactivity disorder (ADHD) outcomes such as atypical affective processing and attention, the exact nature of the relations of these characteristics is unknown. We examined in age- and sex-matched adolescents (N = 132; Mage = 14.944, years, SD = .802) with and without ADHD, whether resting state (RS) theta and alpha power or theta and alpha event-related synchronization (ERS) during affect regulation (1) differ between adolescents with and without ADHD; (2) are differentially associated with event-related potential (ERP) and parent- and self-report measures of affective processing and inattention, given ADHD status and sex, and (3) are differentially lateralized, given ADHD status and sex. Adolescents with ADHD exhibited lower RS frontal-midline alpha power than adolescents without ADHD. In adolescents with ADHD, right parietal theta ERS was positively associated with the ERP measure of elaborate affective/motivational processing and right parietal RS alpha power was negatively associated with self-reported positive affectivity. In adolescents without ADHD, associations were nonsignificant. There was no disassociation of theta and alpha activity with affective processing and inattention. Consistent with clinical impressions, the between-group difference in frontal-midline theta ERS was more marked in boys than girls.

REM Sleep Microstates in the Human Anterior Thalamus.

Rapid eye movement (REM) sleep is an elusive neural state that is associated with a variety of functions from physiological regulatory mechanisms to complex cognitive processing. REM periods consist of the alternation of phasic and tonic REM microstates that differ in spontaneous and evoked neural activity. Although previous studies indicate, that cortical and thalamocortical activity differs across phasic and tonic microstates, the characterization of neural activity, particularly in subcortical structures that are critical in the initiation and maintenance of REM sleep is still limited in humans. Here, we examined electric activity patterns of the anterior nuclei of the thalamus as well as their functional connectivity with scalp EEG recordings during REM microstates and wakefulness in a group of epilepsy patients (N = 12, 7 females). Anterothalamic local field potentials (LFPs) showed increased high-α and ß frequency power in tonic compared with phasic REM, emerging as an intermediate state between phasic REM and wakefulness. Moreover, we observed increased thalamocortical synchronization in phasic compared with tonic REM sleep, especially in the slow and fast frequency ranges. Wake-like activity in tonic REM sleep may index the regulation of arousal and vigilance facilitating environmental alertness. On the other hand, increased thalamocortical synchronization may reflect the intrinsic activity of frontolimbic networks supporting emotional and memory processes during phasic REM sleep. In sum, our findings highlight that the heterogeneity of phasic and tonic REM sleep is not limited to cortical activity, but is also manifested by anterothalamic LFPs and thalamocortical synchronization.SIGNIFICANCE STATEMENT REM sleep is a heterogeneous sleep state that features the alternation of two microstates, phasic and tonic rapid eye movement (REM). These states differ in sensory processing, awakening thresholds, and cortical activity. Nevertheless, the characterization of these microstates, particularly in subcortical structures is still limited in humans. We had the unique opportunity to examine electric activity patterns of the anterior nuclei of the thalamus (ANTs) as well as their functional connectivity with scalp EEG recordings during REM microstates and wakefulness. Our findings show that the heterogeneity of phasic and tonic REM sleep is not limited to cortical activity, but is also manifested in the level of the thalamus and thalamocortical networks.

Thalamic activity during scalp slow waves in humans.

Slow waves are major pacemakers of NREM sleep oscillations. While slow waves themselves are mainly generated by cortical neurons, it is not clear what role thalamic activity plays in the generation of some oscillations grouped by slow waves, and to what extent thalamic activity during slow waves is itself driven by corticothalamic inputs. To address this question, we simultaneously recorded both scalp EEG and local field potentials from six thalamic nuclei (bilateral anterior, mediodorsal and ventral anterior) in fifteen epileptic patients (age-range: 17-64 years, 7 females) undergoing Deep Brain Stimulation Protocol and assessed the temporal evolution of thalamic activity relative to scalp slow waves using time-frequency analysis. We found that thalamic activity in all six nuclei during scalp slow waves is highly similar to what is observed on the scalp itself. Slow wave downstates are characterized by delta, theta and alpha activity and followed by beta, high sigma and low sigma activity during subsequent upstates. Gamma activity in the thalamus is not significantly grouped by slow waves. Theta and alpha activity appeared first on the scalp, but sigma activity appeared first in the thalamus. These effects were largely independent from the scalp region in which SWs were detected and the precise identity of thalamic nuclei. Our results suggest that while small thalamocortical neuron assemblies may initiate cortical oscillations, especially in the sleep spindle range, the large-scale neuronal activity in the thalamus which is detected by field potentials is principally driven by global cortical activity, and thus it is highly similar to what is observed on the scalp.

Sleep-spindle frequency: Overnight dynamics, afternoon nap effects, and possible circadian modulation.

Homeostatic and circadian processes play a pivotal role in determining sleep structure, timing, and quality. In sharp contrast with the wide accessibility of the electroencephalogram (EEG) index of sleep homeostasis, an electrophysiological measure of the circadian modulation of sleep is still unavailable. Evidence suggests that sleep-spindle frequencies decelerate during biological night. In order to test the feasibility of measuring this marker in common polysomnographic protocols, the Budapest-Munich database of sleep records (N = 251 healthy subjects, 122 females, age range: 4-69 years), as well as an afternoon nap sleep record database (N = 112 healthy subjects, 30 females, age range: 18-30 years) were analysed by the individual adjustment method of sleep-spindle analysis. Slow and fast sleep-spindle frequencies were characterised by U-shaped overnight dynamics, with highest values in the first and the fourth-to-fifth sleep cycle and the lowest values in the middle of the sleeping period (cycles two to three). Age-related attenuation of sleep-spindle deceleration was evident. Estimated phases of the nadirs in sleep-spindle frequencies were advanced in children as compared to other age groups. Additionally, nap sleep spindles were faster than night sleep spindles (0.57 and 0.39 Hz difference for slow and fast types, respectively). The fine frequency resolution analysis of sleep spindles is a feasible method of measuring the assumed circadian modulation of sleep. Moreover, age-related attenuation of circadian sleep modulation might be measurable by assessing the overnight dynamics in sleep-spindle frequency. Phase of the minimal sleep-spindle frequency is a putative biomarker of chronotype.

The effects of attention and task-relevance on the processing of syntactic violations during listening to two concurrent speech streams.

The notion of automatic syntactic analysis received support from some event-related potential (ERP) studies. However, none of these studies tested syntax processing in the presence of a concurrent speech stream. Here we present two concurrent continuous speech streams, manipulating two variables potentially affecting speech processing in a fully crossed design: attention (focused vs. divided) and task (lexical - detecting numerals vs. syntactical - detecting syntactic violations). ERPs elicited by syntactic violations and numerals as targets were compared with those for distractors (task-relevant events in the unattended speech stream) and attended and unattended task-irrelevant events. As was expected, only target numerals elicited the N2b and P3 components. The amplitudes of these components did not significantly differ between focused and divided attention. Both task-relevant and task-irrelevant syntactic violations elicited the N400 ERP component within the attended but not in the unattended speech stream. P600 was only elicited by target syntactic violations. These results provide no support for the notion of automatic syntactic analysis. Rather, it appears that task-relevance is a prerequisite of P600 elicitation, implying that in-depth syntactic analysis occurs only for attended speech under everyday listening situations.

The effects of rhythm and melody on auditory stream segregation.

While many studies have assessed the efficacy of similarity-based cues for auditory stream segregation, much less is known about whether and how the larger-scale structure of sound sequences support stream formation and the choice of sound organization. Two experiments investigated the effects of musical melody and rhythm on the segregation of two interleaved tone sequences. The two sets of tones fully overlapped in pitch range but differed from each other in interaural time and intensity. Unbeknownst to the listener, separately, each of the interleaved sequences was created from the notes of a different song. In different experimental conditions, the notes and/or their timing could either follow those of the songs or they could be scrambled or, in case of timing, set to be isochronous. Listeners were asked to continuously report whether they heard a single coherent sequence (integrated) or two concurrent streams (segregated). Although temporal overlap between tones from the two streams proved to be the strongest cue for stream segregation, significant effects of tonality and familiarity with the songs were also observed. These results suggest that the regular temporal patterns are utilized as cues in auditory stream segregation and that long-term memory is involved in this process.

Mobile sleep EEG suggests delayed brain maturation in adolescents with ADHD: A focus on oscillatory spindle frequency.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder. Although data show ADHD is associated with sleep problems, approaches to analyze the association between ADHD and sleep electrophysiology are limited to a few methods with circumscribed foci. AIMS: Sleep EEG was analyzed by a mixed-radix FFT routine and power spectrum parametrization in adolescents with ADHD and adolescents not at-risk for ADHD. Spectral components of sleep EEG were analyzed employing a novel, model-based approach of EEG power spectra. METHODS AND PROCEDURES: The DREEM mobile polysomnography headband was used to record home sleep EEG from 19 medication-free adolescents with ADHD and 29 adolescents not at-risk for ADHD (overall: N = 56, age range 14-19 years) and groups were compared on characteristics of NREM sleep. OUTCOMES AND RESULTS: Adolescents with ADHD exhibited lower frequency of spectral peaks indicating sleep spindle oscillations whereas adolescents not at-risk for ADHD showed lower spectral power in the slow sleep spindle and beta frequency ranges. CONCLUSIONS AND IMPLICATIONS: The observed between-groups difference might indicate delayed brain maturity unraveled during sleep in ADHD.

The effects of aging and hearing impairment on listening in noise.

The study investigates age-related decline in listening abilities, particularly in noisy environments, where the challenge lies in extracting meaningful information from variable sensory input (figure-ground segregation). The research focuses on peripheral and central factors contributing to this decline using a tone-cloud-based figure detection task. Results based on behavioral measures and event-related brain potentials (ERPs) indicate that, despite delayed perceptual processes and some deterioration in attention and executive functions with aging, the ability to detect sound sources in noise remains relatively intact. However, even mild hearing impairment significantly hampers the segregation of individual sound sources within a complex auditory scene. The severity of the hearing deficit correlates with an increased susceptibility to masking noise. The study underscores the impact of hearing impairment on auditory scene analysis and highlights the need for personalized interventions based on individual abilities.

Two effects of perceived speaker similarity in resolving the cocktail party situation - ERPs and functional connectivity.

Following a speaker in multi-talker environments requires the listener to separate the speakers' voices and continuously focus attention on one speech stream. While the dissimilarity of voices may make speaker separation easier, it may also affect maintaining the focus of attention. To assess these effects, electrophysiological (EEG) and behavioral data were collected from healthy young adults while they listened to two concurrent speech streams performing an online lexical detection task and an offline recognition memory task. Perceptual speaker similarity was manipulated on four levels: identical, similar, dissimilar, and opposite-gender speakers. Behavioral and electrophysiological data suggested that, while speaker similarity hinders auditory stream segregation, dissimilarity hinders maintaining the focus of attention by making the to-be-ignored speech stream more distracting. Thus, resolving the cocktail party situation poses different problems at different levels of perceived speaker similarity, resulting in different listening strategies.

Speech prosody supports speaker selection and auditory stream segregation in a multi-talker situation.

To process speech in a multi-talker environment, listeners need to segregate the mixture of incoming speech streams and focus their attention on one of them. Potentially, speech prosody could aid the segregation of different speakers, the selection of the desired speech stream, and detecting targets within the attended stream. For testing these issues, we recorded behavioral responses and extracted event-related potentials and functional brain networks from electroencephalographic signals recorded while participants listened to two concurrent speech streams, performing a lexical detection and a recognition memory task in parallel. Prosody manipulation was applied to the attended speech stream in one group of participants and to the ignored speech stream in another group. Naturally recorded speech stimuli were either intact, synthetically F0-flattened, or prosodically suppressed by the speaker. Results show that prosody - especially the parsing cues mediated by speech rate - facilitates stream selection, while playing a smaller role in auditory stream segmentation and target detection.

Do we parse the background into separate streams in the cocktail party?

In the cocktail party situation, people with normal hearing usually follow a single speaker among multiple concurrent ones. However, there is no agreement in the literature as to whether the background is segregated into multiple streams/speakers. The current study varied the number of concurrent speech streams and investigated target detection and memory for the contents of a target stream as well as the processing of distractors. A male-voiced target stream was either presented alone (single-speech), together with one male-voiced distractor (one-distractor), or a male- and a female-voiced distractor (two-distractor). Behavioral measures of target detection and content tracking performance as well as target- and distractor detection related event-related brain potentials (ERPs) were assessed. We found that the N2 amplitude decreased whereas the P3 amplitude increased from the single-speech to the concurrent speech streams conditions. Importantly, the behavioral effect of distractors differed between the conditions with one vs. two distractor speech streams and the non-zero voltages in the N2 time window for distractor numerals and in the P3 time window for syntactic violations appearing in the non-target speech stream significantly differed between the one- and two-distractor conditions for the same (male) speaker. These results support the notion that the two background speech streams are segregated, as they show that distractors and syntactic violations appearing in the non-target streams are processed even when two speech non-target speech streams are delivered together with the target stream.

Overnight dynamics in scale-free and oscillatory spectral parameters of NREM sleep EEG.

Unfolding the overnight dynamics in human sleep features plays a pivotal role in understanding sleep regulation. Studies revealed the complex reorganization of the frequency composition of sleep electroencephalogram (EEG) during the course of sleep, however the scale-free and the oscillatory measures remained undistinguished and improperly characterized before. By focusing on the first four non-rapid eye movement (NREM) periods of night sleep records of 251 healthy human subjects (4-69 years), here we reveal the flattening of spectral slopes and decrease in several measures of the spectral intercepts during consecutive sleep cycles. Slopes and intercepts are significant predictors of slow wave activity (SWA), the gold standard measure of sleep intensity. The overnight increase in spectral peak sizes (amplitudes relative to scale-free spectra) in the broad sigma range is paralleled by a U-shaped time course of peak frequencies in frontopolar regions. Although, the set of spectral indices analyzed herein reproduce known age- and sex-effects, the interindividual variability in spectral slope steepness is lower as compared to the variability in SWA. Findings indicate that distinct scale-free and oscillatory measures of sleep EEG could provide composite measures of sleep dynamics with low redundancy, potentially affording new insights into sleep regulatory processes in future studies.

Scale-free and oscillatory spectral measures of sleep stages in humans.

Power spectra of sleep electroencephalograms (EEG) comprise two main components: a decaying power-law corresponding to the aperiodic neural background activity, and spectral peaks present due to neural oscillations. "Traditional" band-based spectral methods ignore this fundamental structure of the EEG spectra and thus are susceptible to misrepresenting the underlying phenomena. A fitting method that attempts to separate and parameterize the aperiodic and periodic spectral components called "fitting oscillations and one over f" (FOOOF) was applied to a set of annotated whole-night sleep EEG recordings of 251 subjects from a wide age range (4-69 years). Most of the extracted parameters exhibited sleep stage sensitivity; significant main effects and interactions of sleep stage, age, sex, and brain region were found. The spectral slope (describing the steepness of the aperiodic component) showed especially large and consistent variability between sleep stages (and low variability between subjects), making it a candidate indicator of sleep states. The limitations and arisen problems of the FOOOF method are also discussed, possible solutions for some of them are suggested.

Who said what? The effects of speech tempo on target detection and information extraction in a multi-talker situation: An ERP and functional connectivity study.

People with normal hearing can usually follow one of the several concurrent speakers. Speech tempo affects both the separation of concurrent speech streams and information extraction from them. The current study varied the tempo of two concurrent speech streams to investigate these processes in a multi-talker situation. Listeners performed a target-detection and a content-tracking task, while target-related ERPs and functional brain networks sensitive to speech tempo were extracted from the EEG signal. At slower than normal speech tempo, building the two streams required longer processing times, and possibly the utilization of higher-order, for example, syntactic and semantic cues. The observed longer reaction times and higher connectivity strength in a theta band network associated with frontal control over auditory/speech processing are compatible with this notion. With increasing tempo, target detection performance decreased and the N2b and the P3b amplitudes increased. These data suggest an increased need for strictly allocating target-detection-related resources at higher tempo. This was also reflected by the observed increase in the strength of gamma-band networks within and between frontal, temporal, and cingular areas. At the fastest tested speech tempo, there was a sharp drop in recognition memory performance, while target detection performance increased compared to the normal speech tempo. This was accompanied by a significant increase in the strength of a low alpha network associated with the suppression of task-irrelevant speech. These results suggest that participants prioritized the immediate target detection task over the continuous content tracking, likely due to some capacity limit reached the fastest speech tempo.

A set of composite, non-redundant EEG measures of NREM sleep based on the power law scaling of the Fourier spectrum.

Features of sleep were shown to reflect aging, typical sex differences and cognitive abilities of humans. However, these measures are characterized by redundancy and arbitrariness. Our present approach relies on the assumptions that the spontaneous human brain activity as reflected by the scalp-derived electroencephalogram (EEG) during non-rapid eye movement (NREM) sleep is characterized by arrhythmic, scale-free properties and is based on the power law scaling of the Fourier spectra with the additional consideration of the rhythmic, oscillatory waves at specific frequencies, including sleep spindles. Measures derived are the spectral intercept and slope, as well as the maximal spectral peak amplitude and frequency in the sleep spindle range, effectively reducing 191 spectral measures to 4, which were efficient in characterizing known age-effects, sex-differences and cognitive correlates of sleep EEG. Future clinical and basic studies are supposed to be significantly empowered by the efficient data reduction provided by our approach.

The effects of speech processing units on auditory stream segregation and selective attention in a multi-talker (cocktail party) situation.

Speech unfolds at different time scales. Therefore, neuronal mechanisms involved in speech processing should likewise operate at different (corresponding) time scales. The present study aimed to identify speech units relevant for selecting speech streams in a multi-talker situation. Functional connectivity was extracted from the continuous EEG while young adults detected targets within one stream in the presence of a different, task-irrelevant stream. In two separate groups, either the attended or the ignored stream was manipulated so that it contained intact, word-wise scrambled, syllable-wise scrambled, or spectrally scrambled speech. We found functional brain networks that were sensitive to the difference between the situations when speech was meaningful at sentence vs. at word level, but not between when speech was meaningful at word vs. only valid at syllable level, irrespective of whether the speech units were manipulated in the attended or the ignored stream. These functional brain networks operated in the delta and theta bands corresponding to integrating information from longer time windows. Further, the networks, which could be linked with suppressing information from the to-be-ignored stream included brain areas associated with high-level processing of speech. These results are compatible with late filtering models of auditory attention, as they suggest that the length of intact speech units in the to-be-ignored stream affects processes of attentional selection. However, we found no evidence for speech-to-brain coupling differences as a function of the intact unit of speech in either stream. Thus, although the current results do not rule out that early processes of speech processing affect stream selection in a cocktail party situation, neither do they provide supporting for it.

Linguistic predictability influences auditory stimulus classification within two concurrent speech streams.

Acoustic predictability has been shown to affect auditory stream segregation, while linguistic predictability is known to be an important factor in speech comprehension. We tested the effects of linguistic predictability on auditory stream segregation and target detection by assessing the event-related potentials elicited by targets and distractors in participants presented with two concurrent speech streams. The linguistic cues of predictability varied over four levels. In the three real speech conditions, natural speech was presented with intact phonotactics and sentence prosody: normal speech, word-salad (randomized word order within each sentence), and pseudo-words (randomized syllable order within each sentence). The fourth (control) condition delivered a spectrally rotated version of the normal speech condition. Participants were instructed to attend one stream and respond to the natural cough sounds embedded in it. Coughs were present in both streams, serving as targets in the attended and as distractors in the unattended stream. We expected improved target detection with increasing linguistic predictability. The target-related N2b component's amplitude monotonically increased from the pseudo-word to the word-salad and normal speech condition, while no predictability effects were observed for the P3b amplitude or for behavioral responses. The dissociation between the N2b and P3b/behavioral effect suggests that while linguistic predictability enhanced the process of classifying stimuli as potential targets, this did not affect their detection. Furthermore, the observed nonmonotonic distractor N2 (probably MMN) amplitude increase with increasing linguistic predictability is compatible with the notion that linguistic predictability can modulate auditory stream segregation and/or stream selection.

Neuronal Correlates of Informational and Energetic Masking in the Human Brain in a Multi-Talker Situation.

Human listeners can follow the voice of one speaker while several others are talking at the same time. This process requires segregating the speech streams from each other and continuously directing attention to the target stream. We investigated the functional brain networks underlying this ability. Two speech streams were presented simultaneously to participants, who followed one of them and detected targets within it (target stream). The loudness of the distractor speech stream varied on five levels: moderately softer, slightly softer, equal, slightly louder, or moderately louder than the attended. Performance measures showed that the most demanding task was the moderately softer distractors condition, which indicates that a softer distractor speech may receive more covert attention than louder distractors and, therefore, they require more cognitive resources. EEG-based measurement of functional connectivity between various brain regions revealed frequency-band specific networks: (1) energetic masking (comparing the louder distractor conditions with the equal loudness condition) was predominantly associated with stronger connectivity between the frontal and temporal regions at the lower alpha (8-10 Hz) and gamma (30-70 Hz) bands; (2) informational masking (comparing the softer distractor conditions with the equal loudness condition) was associated with a distributed network between parietal, frontal, and temporal regions at the theta (4-8 Hz) and beta (13-30 Hz) bands. These results suggest the presence of distinct cognitive and neural processes for solving the interference from energetic vs. informational masking.