Adolescent Binge Drinking Is Associated With Accelerated Decline of Gray Matter Volume.

The age- and time-dependent effects of binge drinking on adolescent brain development have not been well characterized even though binge drinking is a health crisis among adolescents. The impact of binge drinking on gray matter volume (GMV) development was examined using 5 waves of longitudinal data from the National Consortium on Alcohol and NeuroDevelopment in Adolescence study. Binge drinkers (n = 166) were compared with non-binge drinkers (n = 82 after matching on potential confounders). Number of binge drinking episodes in the past year was linked to decreased GMVs in bilateral Desikan-Killiany cortical parcellations (26 of 34 with P < 0.05/34) with the strongest effects observed in frontal regions. Interactions of binge drinking episodes and baseline age demonstrated stronger effects in younger participants. Statistical models sensitive to number of binge episodes and their temporal proximity to brain volumes provided the best fits. Consistent with prior research, results of this study highlight the negative effects of binge drinking on the developing brain. Our results present novel findings that cortical GMV decreases were greater in closer proximity to binge drinking episodes in a dose-response manner. This relation suggests a causal effect and raises the possibility that normal growth trajectories may be reinstated with alcohol abstinence.

Dissociation of preparatory attention and response monitoring maturation during adolescence.

OBJECTIVE: Substantial brain development occurs during adolescence providing the foundation for functional advancement from stimulus-bound "bottom-up" to more mature executive-driven "top-down" processing strategies. The objective was to assess development of EEG markers of these strategies and their role in both preparatory attention (contingent negative variation, CNV) and response monitoring (Error Related Negativity, ERN, and Correct Related Negativity, CRN). METHODS: CNV, ERN and CRN were assessed in 38 adolescents (18 girls), age 11-18 years, using a variation of a letter discrimination task. RESULTS: Accuracy increased with age and developmental stage. Younger adolescents used a posterior attention network involved in inhibiting irrelevant information. Activity in this juvenile network, as indexed by a posteriorly-biased CNV and CRN decreased with age and advancing pubertal development. Although enhanced frontal CNV, known to be predictive of accuracy in adults, was not detected even in the older adolescents, top-down medial frontal response monitoring processes (ERN) showed evidence of development within the age-range studied. CONCLUSIONS: The data revealed a dissociation of developmental progress, marked by relatively delayed onset of frontal preparatory attention relative to error monitoring. SIGNIFICANCE: This dissociation may render adolescents vulnerable to excessive risk-taking and disinhibited behavior imposed by asynchronous development of component cognitive control processes.

Respiratory-related evoked potentials during sleep in children.

STUDY OBJECTIVES: The respiratory related evoked potential (RREP) has been previously recorded in children and adults during wakefulness and in adults during sleep. However, there have been no data on RREP during sleep in children. We thus examined children during sleep to determine whether early RREP components would be maintained during all sleep DESIGN AND PARTICIPANTS: Twelve healthy, nonsnoring children, aged 5-12 years, screened by polysomnography and found to have no sleep disorders were assessed during stage 2 sleep, slow wave sleep, and REM sleep. Brief occlusions were presented via an occlusion valve at the inspiratory port of a non-rebreathing valve as interruptions of inspiration. EEG responses were averaged and assessed for the presence of early and late RREP components. RESULTS: Robust early components were seen in the majority of subjects in all sleep stages. Late components were also present, although with some apparent differences compared to those previously reported in adults (using the same recording protocol and an almost identical method of stimulus presentation). Specifically, N350 and N550 were less readily differentiated as separate components, and the N550 did not display the clear anterior-posterior amplitude gradient that is ubiquitous in adults. CONCLUSION: Cortical processing of respiratory-related information persists throughout sleep in children. The pattern of activation in the late components appear to reflect differences in the structure of the developing brain prior to the process of dendritic pruning associated with adolescence.

Changes in cardiovascular function during the sleep onset period in young adults.

Blood pressure (BP) and heart rate (HR) are influenced by the sleep-wake cycle, with relatively abrupt falls occurring in association with sleep onset (SO). However, the pattern and rate of fall in BP and HR during SO and the processes that contribute to the fall in these variables have not been fully identified. Continuous BP and HR recordings were collected beginning 1 h before lights out (LO) until the end of the first non-rapid eye movement sleep period in 21 young, healthy participants maintained in a supine position. Five consecutive phases were defined: 1) the 30 min of wakefulness before LO; 2) LO to stage 1 sleep; 3) stage 1 to stage 2 sleep; 4) stage 2 sleep to the last microarousal before stable sleep; and 5) the first 30 min of undisturbed stable sleep. The data were analyzed on a beat-by-beat basis and reported as 2-min periods for phases 1 and 5 and 10% epochs for phases 2, 3, and 4 (as participants had variable time periods in these phases). The level of baroreflex (BR) activity was assessed by the sequence technique and an autoregressive multivariate model. Furthermore, during phases 3 and 4, the BP and HR responses to arousal from sleep were determined. There were substantial falls in BP and HR after LO before the initial onset of theta;-activity (phase 3) and again after the onset of stable sleep after the cessation of spontaneous arousals. During phases 3 and 4 when there were repeated arousals from sleep, the fall in both variables was retarded. Furthermore, both the rate and magnitude of the fall in BP were negatively associated with the number of arousals during phases 3 and 4. There was a small increase in the sensitivity of the BR and indirect evidence of a substantial fall in its set point.

Association between apolipoprotein E epsilon4 and sleep-disordered breathing in adults.

CONTEXT: Apolipoprotein E epsilon4(ApoE epsilon4) is a well-known risk factor for Alzheimer disease and cardiovascular disease. Sleep-disordered breathing occurs in Alzheimer disease patients and increases risks for cardiovascular disease. Complex interactions among sleep, brain pathology, and cardiovascular disease may occur in ApoE epsilon4 carriers. OBJECTIVE: To study whether genetic variation at the level of ApoE is associated with sleep-disordered breathing or sleep abnormalities in the general population. DESIGN, SETTING, AND PARTICIPANTS: Ongoing longitudinal cohort study of sleep disorders at a US university beginning in 1989, providing a population-based probability sample of 791 middle-aged adults (mean [SD] age, 49 [8] years; range, 32-68 years). MAIN OUTCOME MEASURE: Nocturnal polysomnography to evaluate apnea-hypopnea index. RESULTS: The probability of moderate-to-severe sleep-disordered breathing (apnea-hypopnea index >/=15%) was significantly higher in participants with epsilon4, independent of age, sex, body mass index, and ethnicity (12.0% vs 7.0%; P =.003). Mean (SEM) apnea-hypopnea index was also significantly higher in participants with ApoE epsilon4 (6.5 [0.6] vs 4.8 [0.3]; P =.01). These effects increased with the number of ApoE epsilon4 alleles carried. CONCLUSIONS: A significant portion of sleep-disordered breathing is associated with ApoE epsilon4 in the general population.

The investigation of K-complex and vertex sharp wave activity in response to mid-inspiratory occlusions and complete obstructions to breathing during NREM sleep.

STUDY OBJECTIVES: To determine whether the cortical response to mid-inspiratory occlusions can be used as a model of the cortical response to obstructive events during sleep; and to determine whether the vertex sharp wave (VSW) and K-complex are exclusive contributors to the N350 and N550 components respectively of the stage 2 sleep event-related potential. DESIGN: Two types of respiratory stimuli were used to elicit evoked potential responses during stage 2 NREM sleep. These were mid-inspiratory occlusions and complete breath obstructions. Trials were grouped according to the type of phasic response elicited; isolated K-complex (KC), VSW associated with a K-complex (VSW/KC), isolated VSW, and no evoked response (other). Evoked responses were averaged separately within these categories. SETTING: Data were collected in the University of Melbourne Sleep Laboratory. PARTICIPANTS: Six young healthy male adults. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Data were recorded from 29 scalp sites referenced to linked ears. Mask pressure (Pm) and airflow were also recorded. Intra-thoracic pressure, as indicated by Pm, reached a more negative level following complete obstructions than brief occlusions. However, both types of respiratory stimuli elicited the two late latency components. Although latency varied across the two respiratory conditions in a manner consistent with the intra-thoracic pressure rise time differences, the elicitation characteristics and topographic distribution of these components did not vary across the two types of stimuli. In addition, an N350 was only present in the average for those categories that included VSWs, while an N550 was only present in those categories that contained K-complexes. CONCLUSIONS: Mid-inspiratory occlusions can be used as a model of obstructive events. VSWs contribute exclusively to the N350 component, while K-complexes contribute exclusively to the N550 component.

The relationship between respiratory-related evoked potentials and the perception of inspiratory resistive loads.

This study investigated the relationship between resistive load magnitude, load magnitude estimation, and the respiratory-related evoked potential. In Part 1, 10 healthy subjects estimated the magnitude of five inspiratory resistive loads. Two subjects were shown to have a markedly reduced slope of the magnitude estimation-resistive load relationship and were suggested to be "poor perceivers" of respiratory stimuli. In Part 2, evoked potentials were recorded from the same 10 subjects using the same resistive loads as Part 1. A log-log plot of the group averaged P1 amplitudes showed a linear relationship with resistive load. Aberrant P3 components were seen in the 2 poor perceiving subjects and one of the 2 showed no late response. In the other 8 subjects, P3 varied as a function of resistive load, being augmented to larger loads. These results provide evidence that P3 may be a key index of the perception of respiratory sensitivity and effort.

Upper airway resistance syndrome. Central electroencephalographic power and changes in breathing effort.

Upper airway resistance syndrome (UARS) is defined by excessive daytime sleepiness and tiredness, and is associated with increased breathing effort. Its polygraphic features involve progressive increases in esophageal pressure (Pes), terminated by arousal (AR) as defined by the American Sleep Disorders Association (ASDA). With the arousal there is an abrupt decrease in Pes, called Pes reversal. However, Pes reversal can be seen without the presence of an AR. We performed spectral analysis on electroencephalographic data from a central lead for both AR and nonarousal (N-AR) events obtained from 15 UARS patients (eight men and seven women). Delta band activity was increased before and surrounding Pes reversal regardless of the presence or absence of AR. In the period after Pes reversal, alpha, sigma, and beta activity showed a greater increase in AR events than in N-AR events. The Pes measures were identical leading up to the point of reversal, but showed a longer-lasting and significantly greater decrease in respiratory effort after an AR. The data indicate that substantial electroencephalographic changes can be identified in association with Pes events, even when ARs cannot be detected according to standard criteria; however, visually identifiable electroencephalographic arousals clearly have a greater impact on ongoing inspiratory effort.

The respiratory-related evoked potential: effects of attention and occlusion duration.

The present study assessed the effects of occlusion duration and attention on components of the respiratory-related evoked potential (RREP). Twenty-nine channel evoked potential recordings were obtained from 12 young adults exposed to a pseudorandom sequence of 100-, 200-, 400-, and 800-ms inspiratory occlusions, under attend and ignore conditions. Results demonstrated that the duration of an inspiratory occlusion does not affect RREP components systematically, highlighting the importance of the onset of the occlusion in producing the cortical responses. Attention resulted in augmentation of the N1, P2, and P3 components but did not affect the early latency Nf and P1 components. P1, N1, and P3 occurred with shorter latencies in the attend condition. One subject with poor duration estimation ability displayed substantially delayed P3 latency. This result highlights the relationship between P3 and perception of respiratory somatosensory information.

The roles of vertex sharp waves and K-complexes in the generation of N300 in auditory and respiratory-related evoked potentials during early stage 2 NREM sleep.

STUDY OBJECTIVES: To determine the scalp topography of the N300 response to stimuli of different modalities and to investigate the relationship of the N300 component to K-complexes and vertex sharp waves seen in the un-averaged EEG. DESIGN: Two experiments were conducted one using auditory; the other using respiratory occlusion stimuli presented during stage 2 sleep. Trials were classified on the basis of whether they produced a K-complex, a vertex sharp wave, or some other response. Auditory stimuli were presented in the form of an oddball paradigm, and averaged separately depending on whether they were "frequent" or "rare". In both experiments, responses were averaged separately based on the appearance of K-complexes, vertex sharps waves, or some "other" response to the stimuli. SETTING: Data were collected in the Melbourne University Sleep Laboratory. PARTICIPANTS: Young healthy male adults, eight in experiment 1 and six in experiment 2. INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: Data were collected from 29 scalp sites. In all cases, N300 amplitude was maximal in the vertex sharp wave averages, despite being clearly present in the averages of K-complexes and "other" responses. The vertex maximal scalp topography of the N300 did not differ across response conditions or as a function of stimulus modality. This is consistent with the N300 being produced by the same intracranial generators in all cases. There were no effects of stimulus or response type on N300 latency. CONCLUSIONS: N300 should be viewed as a multi-modal component with a different underlying generator mechanism than that of the K-complex.

The impact of prestimulus EEG frequency on auditory evoked potentials during sleep onset.

Auditory evoked potentials were recorded during wakefulness, Stage 1, and Stage 2 non-REM sleep using a three-tone auditory oddball paradigm. Stage 1 sleep was divided into trials preceded by alpha and those preceded by theta. A negative wave peaking at about 100 ms, N1, displayed a significant decrease in amplitude with the onset of Stage 2 sleep. A later N2 peaked at about 250 ms in the waking state. This changed into a sleep-specific negative wave peaking at 300 ms (N300) at the alpha-theta transition within Stage 1. The P300 displayed a similar shift to become a P450 in Stage 2 sleep. N550 was specific to Stage 2, and was larger in response to rare, rather than frequent stimuli. There was no evidence of any enhancement to relevant rare stimuli compared with irrelevant rare stimuli.

Respiratory-related evoked potentials during the transition from alpha to theta EEG activity in stage 1 NREM sleep.

It has been argued previously that evoked potential components during Stage 1 sleep in response to both auditory and respiratory stimuli are intermediate between those of wakefulness and Stage 2 sleep. However, state fluctuations in the ECG between alpha and theta during Stage 1 sleep have been linked to changes in a number of respiratory functions including ventilation, upper airway resistance and chemical drive. It was therefore hypothesized that if respiratory related evoked potentials (RREP) were averaged separately for alpha and theta EEG periods during Stage 1 sleep, the alpha RREP would resemble wakefulness and the theta RREP would resemble Stage 2 sleep. RREPs were produced by 250 ms occlusions in 10 subjects. EEG was recorded from 29 scalp sites, referenced to linked ears, together with EOG and EMG. The N1 component was not specifically associated with alpha vs. theta activity, but appeared to be sensitive to any decrease in arousal level, suggesting that it was more related to attention than to changes in the EEG. The late N2 and P300 components were present during wake and Stage 1 alpha. However, in Stage 1 theta, different late components emerged (N300 and P450) that differed in latency, amplitude or topographical distribution from those seen in wakefulness. The P2 proved difficult to interpret, whereas the N550 did not appear until Stage 2 sleep, and as such, was not dependent on alpha/theta state. The results indicate that RREP components are differentially affected by the transition into sleep.

The N550 component of the evoked K-complex: a modality non-specific response?

A large amplitude late negative deflection peaking between 500 and 650 ms is observable in the averaged K-complex wave-form. This peak is thus often labelled the N550. 'N550' appears during stage 2 and is maintained into slow wave sleep but is not apparent during REM. Most studies have employed auditory stimuli to elicit the K-complex. Two experiments were run to examine the effects of stimulus modality on the topographical distribution of the N550. In the first experiment, the K-complexes were elicited in an auditory oddball procedure. In the second experiment, K-complexes were elicited by respiratory occlusions. Twenty-nine channel recordings were used to increase spatial resolution. N550 was substantially larger in the average of trials containing K-complexes than in trials in which a K-complex could not be identified. N550 varied inversely in amplitude with the probability of accordance of the stimulus. The topographic distribution of the N550 was consistent between experiments. It was bilaterally symmetrical and was maximal over fronto-central regions of the scalp. The results indicate that the N550 reflects the activity of a modality non-specific, sleep dependent generator that responds to both interoceptive and external stimulation.

Multichannel EEG analysis of respiratory evoked-potential components during wakefulness and NREM sleep.

Airway occlusion in awake humans produces a somatosensory evoked response called the respiratory-related evoked potential (RREP). In the present study, 29 channel evoked-potential recordings were obtained from seven men who were exposed to 250-ms inspiratory airway occlusions during wakefulness, stage 1, stage 2, and slow-wave sleep. The RREP recorded during wakefulness was similar to previous reports, with the unique observation of an additional short-latency positive peak with a mean latency of 25 ms. Short-latency RREP components were maintained in non-rapid-eye-movement (NREM) sleep. The clearly seen N1 vertex and late positive complex components during wakefulness were markedly attenuated during NREM sleep, and two large negative components (N300 and N550) dominated the sleep RREP. These findings indicate the maintenance of central nervous system monitoring of respiratory afferent information during NREM sleep, presumably to facilitate protective arousal responses to pathophysiological respiratory phenomena.

Load compensation as a function of state during sleep onset.

Ventilation decreases and airway resistance increases with the loss of electroencephalogram alpha activity at sleep onset. The aim of this study was to determine whether reflexive load compensation is lost immediately on the loss of alpha activity. Six healthy male subjects were studied under two conditions (load and control-no load), in three states (continuous alpha, continuous theta, and immediately after a transition from alpha to theta), and in two phases (early and late sleep onset). Ventilation and respiratory timing were measured. A comparison of loaded with control conditions indicated that loading had no effect on inspiratory minute ventilation during continuous alpha (differential effect of 0.00 l/min) and only a small, nonsignificant effect in theta immediately after phase 2 transitions (0.31 l/min), indicating a preservation of load compensation at these times. However, there were significant decreases in inspiratory minute ventilation on loaded trials during continuous theta in phase 2 (0.77 l/min) and phase 3 (1.15 l/min) and during theta immediately after a transition in phase 3 (0.87 l/min), indicating a lack of reflexive load compensation. The results indicate that, because reflex load compensation is state dependent, state-related changes in airway resistance contribute to state-related changes in ventilation during sleep onset. However, this effect was slightly delayed with transitions into theta early in sleep.

Source dipole analysis of the early components of the RREP.

Occlusion of the inspiratory airway produces a series of early RREP components. The predominant early positive and negative peaks are seen over the parietal and frontal scalp respectively and have been hypothesised to represent parallel activation of somatosensory and motor cortices in a manner similar to electrically produced SEP components. An alternative hypothesis is that both components are produced by somatosensory cortex, with the frontally maximal negativity reflecting the activity of a tangential dipole source. Respiratory-related evoked potentials (RREPs) elicited by brief occlusion of the inspiratory airway, were recorded using 29 scalp electrodes from six subjects. Early latency components were analysed using the Electromagnetic Source Estimation (EMSE) program for modelling equivalent electrical dipoles, in order to suggest likely generator sources. Two hypotheses were tested: first, that radial dipoles generated by both pre- (motor cortex) and post-centrally (somatosensory cortex) produce the early components; and second, that generator sources are limited to the somatosensory cortex, with activity recorded as frontally maximal reflecting volume conduction from tangential dipoles. Results were highly consistent between subjects and suggested that Nf-P1 was best accounted for by two post-central and two pre-central radial dipoles supporting the first hypothesis. Locations of generator sources are discussed in relation to anatomical correlates.

Scalp topography of the short-latency components of the respiratory-related evoked potential in children.

Respiratory-related evoked potentials (RREPs) have been elicited by inspiratory occlusion and recorded at electroencephalographic (EEG) sites overlying the somatosensory cortex in adults. The present study was the first to be conducted in normal children and was designed to identify the scalp distribution of the early RREP components. EEG responses to occlusion were recorded from CZ-C3, CZ-C4, and 17 sites referenced to the linked earlobes. The RREP was observed in all subjects in the CZ-C3 and CZ-C4 electrode pairs. The earlobe-referenced recordings revealed two RREP patterns. The P1 and N1 peaks were found in C3, C4, P3, P4, T3, and T4. The RREPs recorded from the F3, F4, F7, and F8 electrodes did not exhibit either the P1 or N1 peaks. A negative peak (NF) occurred approximately 13 ms after the P1 peak. The results show that the RREPs to inspiratory occlusions were present bilaterally but diminished greatly over midline sites. Furthermore, consistent with mechanically and electrically elicited somatosensory evoked potentials, the RREP displayed a polarity inversion over the central sulcus in the early component latency range.

Dose dependent effects of alcohol on visual evoked potentials.

The effects of various alcohol doses on components of the visual evoked potential were investigated. Using a repeated measures, Latin square design, five alcohol dose conditions were administered to ten male subjects: 0.00 (placebo); 0.28; 0.36; 0.54 and 0.72 g/kg total body weight. EEG responses to a reversing checker board stimulus were measured in a standard oddball paradigm. In the alcohol conditions, latencies of the P1 and P2 components of the VEP were unaffected. However, reaction time, and the latencies of N2 and P3 displayed significant dose related increases with increasing blood alcohol levels. Further, RMS power of the P3 complex was reduced by higher alcohol doses, as was the N2-P3 amplitude difference at central and parietal sites. It is concluded that the latency and power of the endogenous components of the VEP are altered by alcohol, without effects being seen in earlier components.