Time Cues Research Articles

Circadian modulation of behavioural stress indicators varies between diurnal and nocturnal fish species

In the wild, most animals experience daily fluctuations in threats and resources that are synchronised with environmental time cues such as the light-dark cycle. Consequently, animals have evolved daily behavioural patterns (i.e., diurnal or nocturnal) that enhance their fitness by, for example, reducing the temporal overlapping with predators. In fish, previous studies revealed stronger physiological stress responses during the resting period of the species. However, little is known about the circadian modulation of stress indicators and how they are influenced by daily behavioural patterns. In this research, we investigated the behavioural stress responses of two farmed fish species with different activity patterns: the diurnal Nile tilapia (Oreochromis niloticus) and the nocturnal tench (Tinca tinca). To this end, we examined the behavioural response of individuals exposed to the diving test every 4 h over a 24 h cycle (n = 12 fish/species/time point). Results indicated that most behavioural indicators varied according to the time of day, aligning with the daily rhythmic pattern of the two species. Tilapia exhibited stronger stress responses to novelty during the dark phase, while tench displayed higher stress during the light phase. This was supported by stress-related behaviours such as freezing and erratic movements (in both tilapia and tench) and bottom-dwelling (in tench only). These results indicated that stress responses peaked during the resting phase of each species, although behavioural indicators exhibiting this daily variation did not completely coincide between the studied species. Overall, these findings suggest interspecific differences in the daily modulation of behavioural stress indicators in farmed fish, an effect with potential relevance for welfare. Understanding the activity rhythmic patterns, resting periods, and associated daily variation in stress for each fish species of interest can precisely help tailor farming procedures to minimise suffering.

Text-independent speaker identification using modified SincNet with robust features from suitable acoustic region and appropriate optimizer for raw audio analysis

Speaker identification is a method of identifying an individual from a set of speakers, and text-independent speaker identification systems allow speakers to utter any phrase without any constraints. This study is focused on raw audio analysis as phase, fine-grained frequency patterns, timing cues, and other minute characteristics are preserved when raw waveforms are processed as compared to handcrafted features like Mel-Frequency Cepstral Coefficients (MFCC) and visual representation of audio-like spectrogram. Due to the depth of information, which includes variations in speech rhythm, pitch, and vocal tract shape, it is beneficial for identifying speakers. The deep learning architecture known as SincNet has gained popularity in speaker identification because of its parametric Sinc functions that allow it to operate directly on the raw audio input. In this paper, we have considered SincNet as the baseline model for speaker identification. The effect of proper speech boundary detection, including high-level features and effective optimizer selection are analysed. The precise identification of the signal start and terminus point is important for eliminating the redundant non-speech regions. We have included endpoint detection module as a pre-processing step in the system. Proper feature extraction and selection are crucial to the model's success. To extract more abstract features from the data, we have added more convolution layers to the original SincNet model. Further, we investigated the hyperparameter tuning protocol's sensitivity to the optimizer and selected the suitable optimizer for raw audio analysis. With all the modifications in the system architecture, we are able to archive improvements of 12.76 %, 13.33 %, and 13.39 % respectively for training, validation, and testing over the original SincNet model. In terms of validation loss, our proposed approach attains 0.35 in comparison to the original SincNet loss of 1.02. With this significant improvement, the total training time is marginally increased by 20 minutes for our proposed model. We have performed our investigation on the LibriSpeech dataset to check the effectiveness of our proposed system in comparison to the other model..

Exposing 24-hour cycles in bile acids of male humans

Bile acids are trans-genomic molecules arising from the concerted metabolism of the human host and the intestinal microbiota and are important for digestion, energy homeostasis and metabolic regulation. While diurnal variation has been demonstrated in the enterohepatic circulation and the gut microbiota, existing human data are poorly resolved, and the influence of the host circadian system has not been determined. Using entrained laboratory protocols, we demonstrate robust daily rhythms in the circulating bile acid pool in healthy male participants. We identify temporal relationships between bile acids and plasma lipids and show that these relationships are lost following sleep deprivation. We also highlight that bile acid rhythmicity is predominantly lost when environmental timing cues are held constant. Here we show that the environment is a stronger determinant of these temporal dynamics than the intrinsic circadian system of the host. This has significance for the intimate relationship between circadian timing and metabolism.

Night shift-induced circadian disruption: links to initiation of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and risk of hepatic cancer.

The circadian system plays a crucial role in regulating metabolic homeostasis at both systemic and tissue levels by synchronizing the central and peripheral clocks with exogenous time cues, known as zeitgebers (such as the light/dark cycle). Our body's behavioral rhythms, including sleep-wake cycles and feeding-fasting patterns, align with these extrinsic time cues. The body cannot effectively rest and repair itself when circadian rhythms are frequently disrupted. In many shift workers, the internal rhythms fail to fully synchronize with the end and start times of their shifts. Additionally, exposure to artificial light at night (LAN), irregular eating patterns, and sleep deprivation contribute to circadian disruption and misalignment. Shift work and jet lag disrupt the normal circadian rhythm of liver activity, resulting in a condition known as "circadian disruption". This disturbance adversely affects the metabolism and homeostasis of the liver, contributing to excessive fat accumulation and abnormal liver function. Additionally, extended working hours, such as prolonged night shifts, may worsen the progression of non-alcoholic fatty liver disease (NAFLD) toward non-alcoholic steatohepatitis (NASH) and increase disease severity. Studies have demonstrated a positive correlation between night shift work (NSW) and elevated liver enzymes, indicative of hepatic metabolic dysfunction, potentially increasing the risk of hepatocellular carcinoma (HCC) related to NAFLD. This review consolidates research findings on circadian disruption caused by NSW, late chronotype, jet lag, and social jet lag, drawing insights from studies involving both humans and animal models that investigate the effects of these factors on circadian rhythms in liver metabolism.

Microgels With Electrostatically Controlled Molecular Affinity to Direct Morphogenesis.

Concentration gradients of soluble signaling molecules-morphogens-determine the cellular organization in tissue development. Morphogen-releasing microgels have shown potential to recapitulate this principle in engineered tissue constructs, however, with limited control over the molecular cues in space and time. Inspired by the functionality of sulfated glycosaminoglycans (sGAGs) in morphogen signaling in vivo, a library of sGAG-based microgels is developed and designated as µGel Units to Instruct Development (µGUIDEs). Adjustment of the microgel's sGAG sulfation patterns and concentration enabled the programming of electrostatic affinities that control the release of morphogens. Based on computational analyses of molecular transport processes, µGUIDEs provided unprecedented precision in the spatiotemporal modulation of vascular endothelial growth factor (VEGF) gradients in a microgel-in-gel vasculogenesis model and kidney organoid cultures. The versatile approach offers new options for creating morphogen signaling centers to advance the understanding of tissue and organ development.

Contribution of Spectral and Temporal Cues in Timbre Recognition among Normal-Hearing and Hearing- Impaired People

Background and Aim: Timbre perception is a multidimensional feature of music perception and hearing loss may deteriorate timbre and instrument recognition. Deficits in timbre recognition may originate from poor temporal or spectral coding of musical notes subsequent to hearing loss However, it is not well understood which of these features are more dominant in instrument recognition with normal hearing and hearing loss. This study aimed to evaluate the relative importance of temporal and spectral cues instrument recognition in people with and without nearing loss. Methods: Two groups of adults with normal-hearing and hearing loss were tested with the timbre subtest of the Clinical Assessment of Music Perception (CAMP). Originally, a series of notes is played with eight musical instruments and participants were asked to identify the played instrument among them. In two other conditions, either the rise time or spectral cues of the same notes were masked using a special masking technique. Among eight instruments. Results: Instrument recognition scores were not significantly different between the original and spectral-manipulated conditions but were lower at the temporal-manipulated condition. The difference between the two groups was significant (p<0.05), where the normal-hearing group recognized the musical instruments significantly better than participants with hearing loss group (p<0.05). Conclusion: Temporal cues may have greater importance on timbre recognition regardless of hearing status. This suggests that the interventions and assistive devices which are designed to improve timbre recognition for people with hearing loss should prioritize improvement in temporal coding. Keywords: Timbre recognition; hearing loss; music; musical instrument; temporal; spectral

12237 Monosynaptic Gabaergic Signaling From Suprachiasmatic Nucleus Neuromedin S Neurons To Preoptic Area Kisspeptin Neurons In Mice

Abstract Disclosure: W.I. Abdulmajeed: None. B.B. Jamieson: None. S.X. Thomas: None. Y. Rim: None. A.G. Novak: None. R.E. Campbell: None. R. Piet: None. In female rodents, projections from suprachiasmatic nucleus (SCN) neurons relay timing cues to the gonadotropin-releasing hormone (GnRH) neuronal network for the preovulatory surge. Kisspeptin (KISS1) neurons of the rostral periventricular area of the third ventricle (RP3V) are thought to integrate these cues with estradiol positive feedback to drive GnRH neuron activity, the gonadotropin surge and ovulation. We recently reported that SCN neuron projections release arginine vasopressin (AVP), thereby stimulating female RP3VKiss[1] neuron action potential firing in an estrous cycle stage-dependent manner. In the SCN, AVP is expressed in a subset of neuromedin S (NMS) neurons, a neuronal population essential for circadian rhythms. Moreover, a previous report indicates that exogenous NMS stimulates LH secretion in female rodents. SCNNMS neurons might, therefore, play a role in timing the preovulatory surge. However, whether SCNNMS neurons project to and regulate the activity of RP3VKISS[1] neurons is currently unknown. To address this question, we combined anterograde viral tract-tracing and channelrhodopsin-2 (ChR2)- assisted circuit mapping. Female mice expressing Cre recombinase in NMS cells (NMS-Cre) received stereotaxic injections in the SCN of adeno-associated viral vectors (AAVs) carrying the Cre-dependent sequence for mCherry. Fluorescence immunohistochemistry revealed that mCherry-expressing fibers come in close apposition with the great majority (>80%) of KISS1-immunoreactive neurons in the RP3V, suggesting a SCNNMS-to-RP3VKISS[1] neuron circuit. To interrogate this circuit, we next injected AAVs carrying Cre-dependent channelrhodopsin (ChR2) in the SCN of female NMS-Cre mice that also express the green fluorescent protein in KISS1 cells. Blue LED light (460-487 nm) activation of ChR2-expressing SCNNMS neuronal fibers in the RP3V evoked postsynaptic currents (PSCs) in most KISS1 neurons recorded in whole-cell voltage clamp (-60 mV) in brain slices. Evoked PSCs had short latencies and were blocked by bath application of 0.5 µM tetrodotoxin (TTX), indicating that they were generated by action potential-dependent release. Addition of 100 µM 4-Aminopyridine (4-AP, a potassium channel blocker) to TTX rescued these responses, indicating the existence of a monosynaptic SCNNMS-to-RP3VKISS[1] connection. In addition, evoked PSCs were suppressed by 5 µM gabazine, a GABAA receptor antagonist, but not by 20 µM NBQX and 50 µM D-AP5, AMPA- and NMDA-type glutamate receptor antagonists, respectively, revealing that SCNNMS projections release GABA onto RP3VKISS[1] neurons. Together, our findings are consistent with SCNNMS neurons extending monosynaptic GABAergic projections to RP3VKISS[1] neurons. Further studies are needed to determine the impact of these projections on RP3VKISS[1] neuron activity and the role they might play in the preovulatory surge. Presentation: 6/1/2024

Individual capacity growth over time in leadership courses: an intra-individual multilevel model approach

PurposeOur study was designed to investigate the longitudinal trajectories of student leader development capacities in a sample of students enrolled in multiple leadership-focused courses across several semesters. Our goal was to assess the degree to which course enrollment was associated with growth over the time that students engage as undergraduates in academic leadership programs, and if so, to assess the shape and speed of capacity change.Design/methodology/approachWe utilized a multilevel intra-individual modeling approach assessing students’ motivation to lead, leader self-efficacy, and leadership skills across multiple data collection points for students in a campus major or minor focused on leadership studies. We compared an unconditional model, a fixed effect model, a random intercept model, a random slope model, and a random slope and intercept model to determine the shape of score trajectories. Our approach was not to collect traditional pre-test and post-test data – choosing to collect data only at the beginning of each semester – to reduce time cues typically inherent within pre-test and post-test collections.FindingsOur results strongly suggested that individual students differ greatly in the degree to which they report the capacity to lead when initially enrolling in their first class. Surprisingly, the various models were unable to predict a pattern of longitudinal leader development through repeated course enrollment in our sample.Originality/valueOur investigation employed statistical methods that are not often utilized in leadership education quantitative research, and also included a data collection effort designed to avoid a linear pre-test/post-test score comparison.

Attentional Bias for Opioids in Taiwanese Heavy Smokers with Chronic Noncancer Pain.

Background and Objectives: Attentional bias (AB) for addictive substances is a feature of attention found in individuals with substance misuse or diagnosed with substance use disorders. When AB exists, the attention of the addicted individual may be quickly oriented to cues related to the addictive substance or be maintained on these cues for a longer time. AB toward opioids was found in Western samples of smokers with chronic noncancer pain. The level of AB was dose-responsive. However, similar studies in the Taiwanese population are lacking. This study compared the patterns of AB for opioid analgesics in Taiwanese participants with chronic noncancer pain to that of individuals without pain. This study aimed to investigate if AB toward opioids is presented in Taiwanese heavy smokers who are on long-term opioid therapy for pain control. Materials and Methods: Participants were grouped into chronic noncancer pain smokers, chronic pain nonsmokers, and smokers without pain, according to smoking habits and whether or not on long-term opioid therapy for pain control. Each participant completed demographic questionnaires, mood scales, and the opioid-related visual probe task. Differences in AB among the groups were compared using a three-way analysis of covariance controlling for daily cigarette consumption. Results: Chronic noncancer pain smokers (n = 17) and chronic pain nonsmokers (n = 16) displayed more severe levels of depression, anxiety, and pain, compared to smokers without pain (n = 28). Only did chronic pain nonsmokers show significant AB for opioid cues that were displayed for a short time. Analysis on reaction time found that smokers without pain consistently responded faster to the tasks. No difference in reaction time was found between the pain groups. Conclusions: The current study did not fully replicate findings from studies that were based in Western countries. Formulary availability and regulatory limitations might have affected patient's perception of prescription opioids in Taiwan. However, chronic pain nonsmokers exhibited initial orientation toward opioid-related cues when daily cigarette consumption was accounted for. According to previous research, this AB for shortly displayed opioid cues can be associated with the expectation of pain relief. The current finding also indicated general psychomotor retardation in individuals who were on long-term use of opioids.

Metacognitive processes accompanying the first stages of autobiographical retrieval in the self-memory system

ABSTRACT According to Conway’s view, Autobiographical memory (AM) construction is accompanied by control processes. These processes range from filtering out relevant memories according to the current context, to generating or elaborating appropriate retrieval cues. These processes can be conceptualised as metacognition, the ability to control and monitor cognitive processes. Experimentally, little has been carried out to support the idea that metacognition is involved in AM. To assess this, we designed a task, the Feeling of Retrieval. Participants had to predict whether cue words would facilitate AM access (i.e., fluent access cues) or not (i.e., limited access cues) in a limited time (either 1 (Exp. 2) or 2 (Exp. 1) s). Later, they retrieved memories in response to both types of cues. Results show that cues judged as fluent access led to better AM generation, as illustrated by AM retrieval latency and a subjective measure of the ease with which the AMs were retrieved. These rapid predictions may rely on epistemic feelings and / or other mnemonic cues such as a partial retrieval of information. This metacognitive access to the earliest stages of AM retrieval illustrates the ability to monitor AM processes as proposed by Conway (2005).

Readjustment of circadian clocks by exercise intervention is a potential therapeutic target for sleep disorders: a narrative review.

Circadian clocks are evolved endogenous biological systems that communicate with environmental cues to optimize physiological processes, such as the sleep-wake cycle, which is nearly related to quality of life. Sleep disorders can be treated using pharmacological strategies targeting melatonin, orexin, or core clock genes. Exercise has been widely explored as a behavioral treatment because it challenges homeostasis in the human body and affects the regulation of core clock genes. Exercise intervention at the appropriate time of the day can induce a phase shift in internal clocks. Although exercise is a strong external time cue for resetting the circadian clock, exercise therapy for sleep disorders remains poorly understood. This review focused on exercise as a potential treatment for sleep disorders by tuning the internal circadian clock. We used scientific paper depositories, including Google Scholar, PubMed, and the Cochrane Library, to identify previous studies that investigated the effects of exercise on circadian clocks and sleep disorders. The exercise-induced adjustment of the circadian clock phase depended on exercise timing and individual chronotypes. Adjustment of circadian clocks through scheduled morning exercises can be appropriately prescribed for individuals with delayed sleep phase disorders. Individuals with advanced sleep phase disorders can synchronize their internal clocks with their living environment by performing evening exercises. Exercise-induced physiological responses are affected by age, sex, and current fitness conditions. Personalized approaches are necessary when implementing exercise interventions for sleep disorders.

Binaural responses to a speech syllable are altered in children with hearing loss: Evidence from the frequency-following response

Background & rationaleIn prior work using non-speech stimuli, children with hearing loss show impaired perception of binaural cues and no significant change in cortical responses to bilateral versus unilateral stimulation. Aims of the present study were to: 1) identify bilateral responses to envelope and spectral components of a speech syllable using the frequency-following response (FFR), 2) determine if abnormalities in the bilateral FFR occur in children with hearing loss, and 3) assess functional consequences of abnormal bilateral FFR responses on perception of binaural timing cues. MethodsA single-syllable speech stimulus (/dα/) was presented to each ear individually and bilaterally. Participants were 9 children with normal hearing (MAge = 12.1 ± 2.5 years) and 6 children with bilateral hearing loss who were experienced bilateral hearing aid users (MAge = 14.0 ± 2.6 years). FFR temporal and spectral peak amplitudes were compared between listening conditions and groups using linear mixed model regression analyses. Behavioral sensitivity to binaural cues were measured by lateralization responses as coming from the right or left side of the head. ResultsBoth temporal and spectral peaks in FFR responses increased in amplitude in the bilateral compared to unilateral listening conditions in children with normal hearing. These measures of “bilateral advantage” were reduced in the group of children with bilateral hearing loss and associated with decreased sensitivity to interaural timing differences. ConclusionThis study is the first to show that bilateral responses in both temporal and spectral domains can be measured in children using the FFR and is altered in children with hearing loss with consequences to binaural hearing.

Steven A. Brown and the synchronization of circadian rhythms by body temperature cycles.

The mammalian circadian timing system has a hierarchical architecture, with a central pacemaker located in the brain's suprachiasmatic nucleus orchestrating rhythms in behaviour and physiology. In cooperation with environmental cycles, it synchronizes the phases of peripheral oscillators operating in most cells of the body. Even cells kept in tissue culture harbour self-sustained and cell-autonomous circadian clocks that keep ticking throughout their lifespan. The master pacemaker in the suprachiasmatic nucleus is synchronized primarily by light-dark cycles, whereas peripheral oscillators are phase entrained by a multitude of systemic signalling pathways. These include pathways depending on feeding-fasting cycles, cellular actin polymerization dynamics, endocrine rhythms and, surprisingly, body temperature oscillations. Using tissue culture and murine models, Steve Brown was the first one to demonstrate that shallow rhythms of mammalian body temperature are timing cues (zeitgebers) for peripheral circadian clocks.

Circadian-independent light regulation of mammalian metabolism.

The daily light-dark cycle is a key zeitgeber (time cue) for entraining an organism's biological clock, whereby light sensing by retinal photoreceptors, particularly intrinsically photosensitive retinal ganglion cells, stimulates the suprachiasmatic nucleus of the hypothalamus, a central pacemaker that in turn orchestrates the rhythm of peripheral metabolic activities. Non-rhythmic effects of light on metabolism have also been long known, and their transduction mechanisms are only beginning to unfold. Here, we summarize emerging evidence that, in mammals, light exposure or deprivation profoundly affects glucose homeostasis, thermogenesis and other metabolic activities in a clock-independent manner. Such light regulation could involve melanopsin-based, intrinsically photosensitive retinal ganglion cell-initiated brain circuits via the suprachiasmatic nucleus of the hypothalamus and other nuclei, or direct stimulation of opsins expressed in the hypothalamus, adipose tissue, blood vessels and skin to regulate sympathetic tone, lipolysis, glucose uptake, mitochondrial activation, thermogenesis, food intake, blood pressure and melanogenesis. These photic signalling events may coordinate with circadian-based mechanisms to maintain metabolic homeostasis, with dysregulation of this system underlying metabolic diseases caused by aberrant light exposure, such as environmental night light and shift work.

Timing of egg-laying in relation to a female’s social environment in European starlings

Abstract It is widely assumed that female birds use nonphotic supplemental cues, including social factors, to fine-tune timing of egg-laying to local conditions, but our knowledge of the nature of these social cues and how they operate remains limited. We analyzed the relationship between a female’s social environment (nearest neighbor distances, residency, female -and- network familiarity, synchrony) and variation in timing of egg-laying in European starlings (Sturnus vulgaris) using individual, residual laying date (controlling for annual variation) and temperature-independent residual laying date (accounting for the effect of ambient temperature on laying date). Female social environment varied systematically with overall spatial distribution of nest-boxes (linear vs clumped boxes) but this was not associated with spatial variation in laying date or temperature-independent residual laying date. We found no evidence for any relationships between individual variation in social environment and individual, residual laying date and only weak evidence for any association with individual, temperature-independent residual laying date. The latter was associated with (1) nearest neighbor distances in the linear habitat, with females nesting closer to neighbors laying earlier than predicted by temperature, but not in the two clumped habitats, and (2) neighbor familiarity: females with an intermediate number of returning females (3/8) laid closest to the predicted date. Finally, despite the fact that synchrony was not associated with other social environment metrics, females with lower laying synchrony among neighbors laid earlier than predicted by temperature. This suggests that some components of the female-female social environment could act as supplemental cues for timing of egg-laying.

Task demand mediates the interaction of spatial and temporal attention

Psychophysical studies typically test attentional mechanisms in isolation, but in everyday life they interact to optimize human behavior. We investigated whether spatial and temporal attention interact in two orientation discrimination experiments that vary in task demand. We manipulated temporal and spatial attention separately and conjointly with well-established methods for testing each spatial or temporal attention. We assessed sensitivity (d′) and reaction time for every combination of spatial and timing cues, each of which was valid, neutral, or invalid. Spatial attention modulated sensitivity (d′) and speed (reaction time) across temporal attention conditions. Temporal attention modulated sensitivity and speed under high- but not low- task demands. Furthermore, spatial and temporal attention interacted for the high-demand task. This study reveals that task demand matters; in a simple task spatial attention suffices to improve performance, whereas in a more demanding task both spatial and temporal attention interact to boost performance, albeit in a subadditive fashion.

Prospective memory performance in veterans with and without histories of mild traumatic brain injury: effect of the apolipoprotein E (APOE) ε4 genotype

ABSTRACT Objective Identifying factors that moderate cognitive outcomes following mild traumatic brain injury (mTBI) is crucial. Prospective memory (PM) is a cognitive domain of interest in mTBI recovery as it may be especially sensitive to TBI-related changes. Since studies show that genetic status – particularly possession of the apolipoprotein E (APOE) ε4 allele – can modify PM performance, we investigated associations between mTBI status and APOE-ε4 genotype on PM performance in a well-characterized sample of Veterans with neurotrauma histories. Methods 59 Veterans (mTBI = 33, Military Controls [MCs] = 26; age range: 24–50; average years post-injury = 10.41) underwent a structured clinical interview, neuropsychological assessment, and genotyping. The Memory for Intentions Test (MIST) measured PM across multiple subscales. ANCOVAs, adjusting for age and posttraumatic stress symptoms, tested the effects of mTBI status (mTBI vs. MC) and ε4 status (ε4+ vs. ε4−) on MIST scores. Results Veterans with mTBI history performed more poorly compared to MCs on the MIST 15-min delay (p=.002, ηp 2 =.160), Time Cue (p = .003, ηp 2 =.157), and PM Total (p = .016, ηp 2 =.102). Those with at least one copy of the ε4 allele performed more poorly compared to ε4- Veterans on the MIST 15-min delay (p = .011, ηp 2 =.113) and PM Total (p = .048, ηp 2 = .071). No significant interactions were observed between mTBI and APOE-ε4 status on MIST outcomes (ps>.25). Within the mTBI group, APOE-ε4+ Veterans performed worse than APOE-ε4− Veterans on the MIST 15-min delay subscale (p = .031, ηp 2 = .150). Conclusions mTBI history and APOE-ε4 genotype status were independently associated with worse PM performance compared to those without head injury histories or possession of the APOE-e4 genotype. Performance on the MIST 15-min delay was worse in Veterans with both risk factors (mTBI history and APOE-ε4 positivity). Findings suggest that genetic status may modify outcomes even in relatively young Veterans with mTBI histories. Future research examining longitudinal associations and links to neuroimaging and biomarker data are needed.

Abstract WP9: Ischemic Stroke Progression After Witnessed Onset in Daytime vs Night-Time

Introduction: Early neurologic deterioration (END) and poor functional outcomes are more frequent with night than daytime onset of ischemic stroke. This variation may be related to: 1) circadian variation endogenous bodily rhythms and/or 2) extrinsic environmental time cues. Methods: To assess the contribution of extrinsic environmental time to ischemic stroke course, we evaluated patients with acute cerebral ischemia (ACI) onset within last 2h, enrolled in the NIH FAST-MAG trial of prehospital neuroprotection, consisting of patients with witnessed/wake onset. Results: Among 1235 ACI patients (ischemic stroke 1033, TIA 202), age was 70.8 [±13.2], 45.3% female, initial NIHSS 7 (IQR 2-15), LKW to randomization 59 mins (IQR 46-80), and 473 (38%) treated with IV lytics. Onset occurred during clock daytime (07:00-22:59) in 1147 (92.9%) and night-time (23:00-06:59) in 88 (7.1%). Patients were similar in 18 baseline characteristics, but night-onset had higher initial SBP (162 vs 155, p=0.01) and longer onset to paramedic times (33m vs 23m, p = 0.0002). Among non-lytic patients, both unadjusted and adjusted clinical outcomes were similar in night vs daytime patients, including END (13.6% vs 16.4%), 90d mRS 0-2 (63.6% vs 58.5%), and 90d mortality (10.2% vs 12.8%). Among lytic patients, clinical outcomes were also similar in night vs daytime onset patients, including unadjusted END (36% vs 21.7%), 90d mRS 0-2 (52% vs 46.9%), and 90d mortality (12% vs 17.4%). Night vs daytime onset did not modify the effect of magnesium vs placebo on outcome among either non-thrombolytic or thrombolytic-treated patients (Figure). Conclusion: Among acute cerebral ischemia patients, efficacy, safety, and neuroprotective agent response outcomes were not modified by witnessed onset during active versus inactive phase clock times. These findings suggest biological wake-sleep state rather than chronologic clock time is the driver of known circadian rhythmicity in stroke course.

Spatial hearing training in virtual reality with simulated asymmetric hearing loss

Sound localization is essential to perceive the surrounding world and to interact with objects. This ability can be learned across time, and multisensory and motor cues play a crucial role in the learning process. A recent study demonstrated that when training localization skills, reaching to the sound source to determine its position reduced localization errors faster and to a greater extent as compared to just naming sources’ positions, despite the fact that in both tasks, participants received the same feedback about the correct position of sound sources in case of wrong response. However, it remains to establish which features have made reaching to sound more effective as compared to naming. In the present study, we introduced a further condition in which the hand is the effector providing the response, but without it reaching toward the space occupied by the target source: the pointing condition. We tested three groups of participants (naming, pointing, and reaching groups) each while performing a sound localization task in normal and altered listening situations (i.e. mild-moderate unilateral hearing loss) simulated through auditory virtual reality technology. The experiment comprised four blocks: during the first and the last block, participants were tested in normal listening condition, while during the second and the third in altered listening condition. We measured their performance, their subjective judgments (e.g. effort), and their head-related behavior (through kinematic tracking). First, people’s performance decreased when exposed to asymmetrical mild-moderate hearing impairment, more specifically on the ipsilateral side and for the pointing group. Second, we documented that all groups decreased their localization errors across altered listening blocks, but the extent of this reduction was higher for reaching and pointing as compared to the naming group. Crucially, the reaching group leads to a greater error reduction for the side where the listening alteration was applied. Furthermore, we documented that, across blocks, reaching and pointing groups increased the implementation of head motor behavior during the task (i.e., they increased approaching head movements toward the space of the sound) more than naming. Third, while performance in the unaltered blocks (first and last) was comparable, only the reaching group continued to exhibit a head behavior similar to those developed during the altered blocks (second and third), corroborating the previous observed relationship between the reaching to sounds task and head movements. In conclusion, this study further demonstrated the effectiveness of reaching to sounds as compared to pointing and naming in the learning processes. This effect could be related both to the process of implementing goal-directed motor actions and to the role of reaching actions in fostering the implementation of head-related motor strategies.

The forbidden zone for sleep is more robust in adolescents compared to adults

IntroductionThe propensity for sleep shifts later as puberty progresses. The present analysis examines whether the circadian-dependent wake maintenance zone, or forbidden zone for sleep observed in the evening just before habitual bedtime is more pronounced in late to post-pubertal adolescents compared to adults and may partly explain late sleep onset in maturing adolescents.MethodsForty four healthy late/post-pubertal adolescents (aged 14.3–17.8 years, 23 female) and 44 healthy adults (aged 30.8–45.8 years, 21 female) participated in an ultradian light/dark protocol for 3 days cycling between 2-h wake periods (~20 lux) and 2-h nap periods (~0 lux) without external time cues. The dim light melatonin onset (DLMO), a measure of circadian phase, was measured immediately before the ultradian protocol by sampling saliva every 30 min in dim light. Wrist actigraphs were used to assess sleep onset latency and total sleep time during the naps that occurred during the ultradian sleep/wake schedule. Sleep episodes were grouped into 2-h bins relative to individual DLMOs (28–56 naps/bin). Sleep onset and total sleep time were compared between adolescents and adults as well as between males and females within each age group.ResultsAdolescents took significantly longer to fall asleep compared to adults during naps that occurred in the 4 h window surrounding the DLMO [2h before DLMO t(50) = 2.13, p = 0.04; 2 h after DLMO t(33) = 3.25, p = 0.003]. Adolescents also slept significantly less than adults during naps that occurred in the 4-h window surrounding DLMO [2 h before DLMO t(51) = −2.91, p = 0.01; 2 h after DLMO t(33) = −1.99, p = 0.05]. Adolescent males slept less than adolescent females in naps that occurred in the 2 h window after the DLMO [t(14) = −2.24, p = 0.04].DiscussionCompared to adults, late/post-pubertal adolescents showed greater difficulty falling asleep and maintaining sleep around the time of their DLMO, which usually occurs a few hours before habitual sleep onset. A greater amplitude in the circadian-driven forbidden zone for sleep could be an additional physiological mechanism explaining why maturing adolescents find it difficult to fall asleep early, increasing the risk for restricted sleep in the context of early school start times.