Tracking auditory mismatch negativity responses during full conscious state and coma.

The mismatch negativity (MMN) is considered the electrophysiological change-detection response of the brain, and therefore a valuable clinical tool for monitoring functional changes associated with return to consciousness after severe brain injury. Using an auditory multi-deviant oddball paradigm, we tracked auditory MMN responses in seventeen healthy controls over a 12-h period, and in three comatose patients assessed over 24 h at two time points. We investigated whether the MMN responses show fluctuations in detectability over time in full conscious awareness, or whether such fluctuations are rather a feature of coma. Three methods of analysis were utilized to determine whether the MMN and subsequent event-related potential (ERP) components could be identified: traditional visual analysis, permutation t-test, and Bayesian analysis. The results showed that the MMN responses elicited to the duration deviant-stimuli are elicited and reliably detected over the course of several hours in healthy controls, at both group and single-subject levels. Preliminary findings in three comatose patients provide further evidence that the MMN is often present in coma, varying within a single patient from easily detectable to undetectable at different times. This highlights the fact that regular and repeated assessments are extremely important when using MMN as a neurophysiological predictor of coma emergence.

Emotional Modulation of Response Inhibition in Adolescents During Acute Suicidal Crisis: Event-Related Potentials in an Emotional Go/NoGo Task.

Objectives. Suicide is the second leading cause of adolescent deaths and may be linked to difficulties with inhibitory and emotional processing. This study assessed the neural correlates of cognitive inhibition during emotional processing in adolescents hospitalized for a suicidal crisis. Methods. Event-related potentials were recorded during an emotional Go/NoGo task in 12 adolescents who attempted suicide and 12 age- and sex-matched healthy controls. Results. Compared to the control group, the suicidal group showed significantly reduced positivity at the time of the P3d (difference waveform reflecting NoGo minus Go trials) in response to happy and neutral, but not sad stimuli. For happy stimuli, this group difference was restricted to the right hemisphere. Further analyses indicated that the suicidal group had a reversed pattern of P3 amplitude in response to inhibition, with lower amplitudes in the NoGo compared to the Go conditions. Suicidal symptoms severity strongly correlated with lower amplitude of the P3d in response to neutral faces. Conclusions. These findings provide more insight into inhibition difficulties in adolescents with acute suicidal risk. Interactions between emotional and inhibition processing should be considered when treating acutely suicidal youths.

The Effects of Total Sleep Deprivation on Attention Capture Processes in Young and Older Adults: An ERP Study.

BACKGROUND: The present study investigated whether sleep deprivation affects attention capture in young and older adults using event-related potentials (ERPs). METHODS: Eleven young adults (20-30 y) and nine older adults (60-70 y) were tested following both normal sleep (NS) and total sleep deprivation (TSD). ERPs were recorded during an auditory discrimination task consisting of standard and deviant stimuli. RESULTS: Deviant stimuli elicited the MMN, P3a, and RON ERPs. TSD attenuated the differences in reaction times between standards and deviants in young adults but not older adults. The P3a was attenuated in older adults compared to young adults. Older adults had a larger RON amplitude compared to young adults following NS, but not TSD. CONCLUSIONS: The reduced P3a and the absence of behavioral performance alteration in the older group suggests that older adults may utilize different neural processing strategies compared to younger adults to compensate for age-related declines in neural resources for attention capture. Sleep loss influenced age-related differences on the RON, suggesting that older adults may have reduced access to compensatory strategies following sleep loss.

Sleep architecture and emotional inhibition processing in adolescents hospitalized during a suicidal crisis.

Background: Suicide is the second leading cause of death in adolescents. Sleep disturbances could alter inhibitory processes and contribute to dangerous behaviors in this critical developmental period. Adolescents in suicidal crisis have been shown to have lighter sleep compared to healthy controls. Additionally, suicidal adolescents have lower neural resources mobilized by emotionally charged inhibition processing. The present exploratory study aimed to determine how sleep architecture in suicidal adolescents may relate to inhibition processing in response to emotional stimuli. Methods: Ten adolescents between 12 and 17 years of age with a diagnosis of major depressive disorder and who attempted suicide were recruited while hospitalized for a suicidal crisis in a psychiatric inpatient unit. Event-related potentials (ERPs) were recorded prior to bedtime during a Go/NoGo task involving pictures of sad, happy, and neutral faces. Polysomnography was then recorded throughout the night. Pearson correlations were conducted to investigate how inhibition performance and ERP parameters reflecting inhibition processing (i.e., P3d and N2d derived from difference waveform calculated as NoGo minus Go trials) relate to sleep architecture. Results: Poorer inhibition accuracy in response to emotional stimuli was significantly correlated with shorter REM sleep latency, higher REM sleep, and more frequent nocturnal awakenings. The P3d in response to sad faces was negatively correlated with NREM2 sleep and positively correlated with NREM3 sleep. No such association with the P3d was found for happy or neutral stimuli. There were no significant correlations for the N2d. Conclusion: Altered sleep in adolescents with depression who are in a suicidal crisisis associated with behavioral inhibition difficulties and fewer neural resources mobilized by inhibitory processes in emotionally charged contexts. This highlights the importance of addressing sleep disturbances while managing suicidal crises in adolescents.

Attentional Bias Deficits in Adolescent Suicide Attempters During an Emotional Stroop Task: An ERP Study.

There is increasing evidence that, in adolescence, attentional bias plays a critical role in the vulnerability for suicidal behaviour. No studies to date have investigated the neurophysiological correlates of attentional bias in adolescent suicidality. The present study uses event-related potentials (ERPs) to investigate such processing in inpatient adolescents admitted for an acute suicide crisis using an Emotional Stroop Task (EST). In this task, participants are asked to name the colour of words varying in emotional valence (positive, negative, neutral, suicide-related). Suicidal individuals are hypothesised to be more preoccupied by the context of the suicide-related stimuli, which may interfere with their ability to perform the colour naming task. Seventeen adolescents with acute suicidal behaviour and 17 age- and gender-matched healthy controls performed an EST while ERPs were recorded. Suicide attempters showed increased reaction times to suicide-related words compared to other emotion categories, while the controls did not. The amplitude of the early posterior negativity (EPN) was not significantly different across groups or emotional valence. A double peak P3 (early-P3 and late-P3) was observed in both groups. Both the early- and late-P3 were significantly reduced in amplitude in the suicide attempter group compared to the control group, regardless of emotional valence. The late-P3 latency was also significantly delayed in the suicide attempters compared to controls. The behavioural findings support the attentional bias theories of suicide attempters and extend these findings to adolescents. Furthermore, large early- and late-P3 provide evidence that cognitive strategies employed by two groups did markedly differ.

The effects of sleep on objective measures of gap detection using a time-efficient multi-deviant paradigm.

Auditory temporal resolution, measured through gap detection, is critical for the perception of speech. A time-efficient multi-deviant paradigm has previously been developed for gap detection. The purpose of the present study was to determine if this multi-deviant paradigm could be used for gap detection during NREM sleep. ERPs were recorded in 10 young adults while awake and during the first two hours of NREM sleep. A multi-deviant paradigm was employed with six different deviants varying in gap duration, ranging from 2 to 40 ms. During waking, a DRN was observed for the 10, 20, 30 and 40 ms gaps. The DRN was absent during sleep. A P2 was present in NREM for the 20, 30 and 40 ms gaps followed by a P3a to the 30 and 40 ms gaps. An N350 was observed following the 10, 20, 30 and 40 ms gaps. Previous studies have reported significant ERPs to gaps having shorter durations than the present study. The multi-deviant paradigm may not be suitable for the determination of gap threshold during sleep. Nevertheless, it provides an exquisite means to determine perceptibility and the extent of processing of longer duration, supra-threshold gaps during sleep.

Active and Passive Attentional Processing in Adolescent Suicide Attempters: An Event-Related Potential Study.

INTRODUCTION: Suicide is the second leading cause of death among adolescents. Suicidal behavior is associated with impairments in attention. Attention can be directed toward relevant events in the environment either actively, under voluntary control, or passively, by external salient events. The extent to which the risk for suicidal behavior affects active and passive attention is largely unknown. METHODS: Event-related potentials (ERPs) were recorded while 14 adolescents with acute suicidal behavior and 14 healthy controls performed an auditory 3-stimulus oddball task. The task consisted of standard (80%), target (10%), and novel (10%) stimuli. The participants were instructed to press a button upon presentation of the target. The novel stimuli were unexpected and irrelevant to the target detection task. RESULTS: Accuracy of target detection was slightly but significantly reduced in the suicidal group. There were no significant differences in the amplitude of the target-N2 or -P3b between groups. There was a slight, but nonsignificant, increase in the amplitude of the novel-N2 and -P3 in the suicidal group. CONCLUSIONS: This is the first study to explore both passive and controlled aspects of attention using ERPs in adolescents with acute suicidal behavior. Although there were no significant ERP group differences, this is an important step in identifying objective markers of suicide risk among adolescents.

A time-efficient multi-deviant paradigm to determine the effects of gap duration on the mismatch negativity.

The insertion of a silent period (or gap) in a frequently occurring standard stimulus elicits a negative-going event-related potential (ERP), called the Deviant-Related Negativity (DRN). This is often studied using a single-deviant paradigm. To study the effects of gaps with multiple durations, a different sequence would be required for each gap. A more time-efficient multi-deviant paradigm has been developed in which stimuli of various gap widths are included in a single sequence. In the present study, 14 young adults watched a silent video while ignoring an auditory sequence. A single run of a multi-deviant sequence was presented in which 6 different rare deviants alternated with a standard stimulus. The standard was a 200-ms white noise burst. The deviants were constructed by inserting a gap in the standard. The duration of the 6 gaps ranged from 2 to 40 ms. Participants were also presented with multiple runs of single-deviant sequences. Each of the 3 deviants was run in a separate sequence. The amplitude of the DRN elicited by the deviant increased as gap duration became longer, although it did plateau for the longer duration gaps. The amplitudes of the DRNs were larger in the single-deviant paradigm than in the multi-deviant paradigm. However, the difference was only significant when the mastoid reference was used. Behavioural data showed a mean d' of 2.1 for the 5-ms gap. None of the participants were able to detect the 2-ms gap. There was no correlation between d' and the DRN amplitude. Still, the effects of gap duration on the amplitude of the DRN were similar between the single and multi-deviant sequences. This makes the multi-deviant paradigm a possible time-saving alternative to the single-deviant paradigm.

Could long-term administration of melatonin to prepubertal children affect timing of puberty? A clinician's perspective.

Exogenous melatonin can be used to treat sleep disturbance in adults, children, and adolescents. While its short-term use is considered safe, there are some concerns that long-term use might delay children's sexual maturation, possibly by disrupting the decline in nocturnal melatonin levels that occur at the onset of puberty. This narrative review aimed to summarize some of the current knowledge about the potential effects of exogenous melatonin on puberty. We found no clinical studies that experimentally tested the effects of melatonin on pubertal timing in children, but we reviewed the small number of observational studies. We also drew on animal data to try to answer our question. The photoperiod and melatonin-mediated seasonal transitions in sexual activity and breeding in some mammals across the seasons have been used as a model of sexual development in mammals, including humans. The switch from non-sexual activity (in the non-breeding period) to sexual activity (in the breeding period) has been likened to the onset of puberty as there are similarities between the two. We conclude that to investigate an association between melatonin and pubertal timing, it will be important to conduct long-term randomized controlled trials of latency age children and also examine the cellular and systems-level interactions between melatonin and kisspeptin, a recently identified neuropeptide with a locus of action at the gonadotropin releasing hormone neurons that is important in contributing to the timing of puberty onset.

Sleep architecture in adolescents hospitalized during a suicidal crisis.

OBJECTIVE/BACKGROUND: Rates of suicide attempts in Canadian youths are concerning. Adolescence is a sensitive period for the emergence of both sleep and mood problems, two major risk factors for suicidality. This naturalistic study aimed to define the sleep profile of adolescents under the combined influence of suicidality, depression and pharmacotherapy during hospitalization for a suicidal crisis. PATIENTS/METHODS: Seventeen suicidal adolescents (15.0 + 1.2years, 82% females) with major depression were recruited from a Canadian pedopsychiatric inpatient unit. Seventeen non-depressed adolescents were retrospectively collated from another database (15.0 + 1.1years, 83% females). None of the participants had a history of sleep disorders or significant medical conditions. RESULTS: Compared to controls, suicidal adolescents had a longer sleep onset latency (Z = -4.5, p < 0.001), longer REM latency (Z = -3.2, p = 0.001), higher percentage of NREM1 sleep t(33) = -2.6, p = 0.020), and higher REM density (Z = -2.8, p = 0.004) than controls. Higher REM density correlated with higher CDI-II scores (r = 0.55, p = 0.27) A significant interaction indicated that the two groups had similar NREM3 percentages in the first two-thirds of the night, but that the suicidal group had significantly lower NREM3 percentage than the controls in the last third of the night (F(2,66) = 3.4, p = 0.041). CONCLUSIONS: Significant sleep abnormalities were observed during hospitalization for a suicidal crisis in a sample of depressed and mostly medicated adolescents. This included sleep initiation and REM sleep latency abnormalities, shallower sleep and high REM density. Future studies should decipher the relative effects of depression, suicidality and medication on sleep. These findings stress the need to address sleep disturbances in the management of suicidality in adolescents.

Event-Related Potential Measures of Attention Capture in Adolescent Inpatients With Acute Suicidal Behavior.

Impaired executive functions, modulated by the frontal lobes, have been suggested to be associated with suicidal behavior. The present study examines one of these executive functions, attentional control, maintaining attention to the task-at-hand. A group of inpatient adolescents with acute suicidal behavior and healthy controls were studied using a passively presented auditory optimal paradigm. This "optimal" paradigm consisted of a series of frequently presented homogenous pure tone "standards" and different "deviants," constructed by changing one or more features of the standard. The optimal paradigm has been shown to be a more time-efficient replacement to the traditional oddball paradigm, which makes it suitable for use in clinical populations. The extent of processing of these "to-be-ignored" auditory stimuli was measured by recording event-related potentials (ERPs). The P3a ERP component is thought to reflect processes associated with the capturing of attention. Rare and novel stimuli may result in an executive decision to switch attention away from the current cognitive task and toward a probe of the potentially more relevant "interrupting" auditory input. On the other hand, stimuli that are quite similar to the standard should not elicit P3a. The P3a has been shown to be larger in immature brains in early compared to later adolescence. An overall enhanced P3a was observed in the suicidal group. The P3a was larger in this group for both the environmental sound and white noise deviants, although only the environmental sound P3a attained significance. Other deviants representing only a small change from the standard did not elicit a P3a in healthy controls. They did elicit a small P3a in the suicidal group. These findings suggest a lowered threshold for the triggering of the involuntary switch of attention in these patients, which may play a role in their reported distractibility. The enhanced P3a is also suggestive of an immature frontal central executive and may provide a promising marker for early identification of some of the risk factors for some of the cognitive difficulties linked to suicidality.

Highly relevant stimuli may passively elicit processes associated with consciousness during the sleep onset period.

Sleep onset marks the transition from waking to sleep, during which conscious awareness of the external environmental is gradually lost. The present study examines the extent of processing of acoustic change during sleep onset. An auditory optimal paradigm was used to record event-related potentials to six deviant stimuli during wakefulness, stage N1, and stage N2 sleep. During waking and early-stage N1, two of the deviants, environmental sounds and white noise, elicited a P3a reflecting processes that may lead to conscious awareness of acoustic change. Surprisingly, the P3a was also observed following both deviants during late-stage N1, a period thought to represent decreased awareness of the environment. Only the environmental sounds continued to elicit a P3a during stage N2 sleep, associated with the loss of consciousness of the external environment. Certain auditory stimuli may thus continue to activate processes that may lead to conscious awareness during the sleep onset period.

Evidence of P3a During Sleep, a Process Associated With Intrusions Into Consciousness in the Waking State.

The present study examines processes associated with intrusions into consciousness during an unconscious state, natural sleep. The definition of sleep is still much debated. Almost all researchers agree that sleep onset represents a gradual loss of consciousness of the external environment. For sleep to be beneficial, it needs to remain as undisturbed as possible. Nevertheless, unlike other unconsciousness states, sleep is reversible. For purposes of survival, it is critical that the sleeper be able to "detect" and perhaps become conscious of highly relevant biological or personal information. Therefore, even in sleep, the brain must decide whether a new incoming stimulus is relevant and if so, may require an arousal to wakefulness, or whether it is irrelevant and can be gated to prevent disruption of sleep. Event-related potentials (ERPs) were used to measure the extent processing of auditory stimuli some of which elicited an ERP component, the P3a, in the waking state. The P3a is associated with processes resulting in the interruption of frontal central executive, leading to conscious awareness. Very little research has focused on the occurrence of the P3a during sleep. A multi-feature paradigm was used to examine the processing of a frequently occurring "standard" stimulus and six rarely occurring different "deviant" stimuli during wakefulness, NREM, and REM sleep. A P3a was elicited by novel environmental sounds and white noise bursts in the waking state, replicating previous studies. Other deviant stimuli (changes in pitch, intensity, duration) failed to do so. The ERPs indicated that processing of the stimuli that did not elicit a P3a in wakefulness were much inhibited during both NREM and REM sleep. Surprisingly, those deviants that did elicit a P3a in wakefulness continued to do so in stage N2 and REM sleep. The subject did not, however, awaken. These results suggest processes leading to consciousness in wakefulness may still remain active during sleep possibly allowing subjects to act on potentially highly relevant input. This may also explain how sleep can be reversed if the stimulus input is sufficiently critical.

Can an auditory multi-feature optimal paradigm be used for the study of processes associated with attention capture in passive listeners?

OBJECTIVE: A rarely occurring and highly relevant auditory stimulus occurring outside of the current focus of attention can cause a switching of attention. Such attention capture is often studied in oddball paradigms consisting of a frequently occurring "standard" stimulus which is changed at odd times to form a "deviant". The deviant may result in the capturing of attention. An auditory ERP, the P3a, is often associated with this process. To collect a sufficient amount of data is however very time-consuming. A more multi-feature "optimal" paradigm has been proposed but it is not known if it is appropriate for the study of attention capture. METHODS: An optimal paradigm was run in which 6 different rare deviants (p=.08) were separated by a standard stimulus (p=.50) and compared to results when 4 oddball paradigms were also run. RESULTS: A large P3a was elicited by some of the deviants in the optimal paradigm but not by others. However, very similar results were observed when separate oddball paradigms were run. CONCLUSIONS & SIGNIFICANCE: The present study indicates that the optimal paradigm provides a very time-saving method to study attention capture and the P3a.

Personal semantics: Is it distinct from episodic and semantic memory? An electrophysiological study of memory for autobiographical facts and repeated events in honor of Shlomo Bentin.

Declarative memory is thought to consist of two independent systems: episodic and semantic. Episodic memory represents personal and contextually unique events, while semantic memory represents culturally-shared, acontextual factual knowledge. Personal semantics refers to aspects of declarative memory that appear to fall somewhere in between the extremes of episodic and semantic. Examples include autobiographical knowledge and memories of repeated personal events. These two aspects of personal semantics have been studied little and rarely compared to both semantic and episodic memory. We recorded the event-related potentials (ERPs) of 27 healthy participants while they verified the veracity of sentences probing four types of questions: general (i.e., semantic) facts, autobiographical facts, repeated events, and unique (i.e., episodic) events. Behavioral results showed equivalent reaction times in all 4 conditions. True sentences were verified faster than false sentences, except for unique events for which no significant difference was observed. Electrophysiological results showed that the N400 (which is classically associated with retrieval from semantic memory) was maximal for general facts and the LPC (which is classically associated with retrieval from episodic memory) was maximal for unique events. For both ERP components, the two personal semantic conditions (i.e., autobiographical facts and repeated events) systematically differed from semantic memory. In addition, N400 amplitudes also differentiated autobiographical facts from unique events. Autobiographical facts and repeated events did not differ significantly from each other but their corresponding scalp distributions differed from those associated with general facts. Our results suggest that the neural correlates of personal semantics can be distinguished from those of semantic and episodic memory, and may provide clues as to how unique events are transformed to semantic memory.

Partial sleep deprivation does not alter processes involved in semantic word priming: event-related potential evidence.

Sleep deprivation has generally been observed to have a detrimental effect on tasks that require sustained attention for successful performance. It might however be possible to counter these effects by altering cognitive strategies. A recent semantic word priming study indicated that subjects used an effortful predictive-expectancy search of semantic memory following normal sleep, but changed to an automatic, effortless strategy following total sleep deprivation. Partial sleep deprivation occurs much more frequently than total sleep deprivation. The present study therefore employed a similar priming task following either 4h of sleep or following normal sleep. The purpose of the study was to determine whether partial sleep deprivation would also lead to a shift in cognitive strategy to compensate for an inability to sustain attention and effortful processing necessary for using the predicative expectancy strategy. Sixteen subjects were presented with word pairs, a prime and a target that were either strongly semantically associated (cat...dog), weakly associated (cow...barn) or not associated (apple...road). The subject's task was to determine if the target word was semantically associated to the prime. A strong priming effect was observed in both conditions. RTs were slower, accuracy lower, and N400 larger to unassociated targets, independent of the amount of sleep. The overall N400 did not differ as a function of sleep. The scalp distribution of the N400 was also similar following both normal sleep and sleep loss. There was thus little evidence of a difference in the processing of the target stimulus as a function of the amount sleep. Similarly, ERPs in the period between the onset of the prime and the subsequent target also did not differ between the normal sleep and sleep loss conditions. In contrast to total sleep deprivation, subjects therefore appeared to use a common predictive expectancy strategy in both conditions. This strategy does however require an effortful sustaining of attention, and may not have been entirely successful when sleep was restricted. A slight but significant decrease in accuracy was noted.