Neuroscience Research

Repetitive Transcranial Magnetic Stimulation (rTMS) is a promising treatment for tobacco use disorder (TUD). Although at a group level, active stimulation outperforms sham, at an individual level, variability exists in clinical response. The behavioral and neurobiological factors that differentiate those who respond to rTMS from those who do not remain unclear. To explore individual factors that influence acute responses to rTMS, N = 60 human participants received one session of rTMS to the dorsolateral prefrontal cortex (DLPFC) and to a control region (visual cortex; V5) in a randomized order. They completed behavioral assessments and neuroimaging before and after rTMS sessions. Hypotheses involving behavioral and neuroimaging predictors of response were pre-registered prior to completion of data collection. rTMS to the DLPFC led to significant reductions in self-reported cigarette craving compared with rTMS to a control brain region (p = 0.0006) and participants were classified as n = 38 responders and n = 22 nonresponders. Responders used significantly more cigarettes per day (M = 11.441) compared to nonresponders (M = 7.952), reported higher levels of cigarette craving (d = 1.059), and more severe nicotine withdrawal (d = 0.803) prior to rTMS. Neuroimaging analyses based on preregistered hypotheses indicated that DLPFC-frontoparietal and insula whole-brain functional connectivity did not differ significantly between responders and nonresponders. However, exploratory analyses revealed that responders had reduced pre-rTMS functional connectivity between the insula and nucleus accumbens, precuneus, and occipital pole. These findings suggest that response to rTMS for TUD is associated with greater baseline cigarette consumption, craving, and withdrawal, in addition to distinct functional connectivity patterns related to salience, reward, and self-referential processes, providing candidate behavioral and neural markers for personalized rTMS interventions for TUD.

Background: Childhood and adolescent hearing loss affects not only communication and cognitive development but also motor skills and school participation. Consequently, it generates inequalities in learning and educational inclusion. Nevertheless, no systematic review has yet analyzed these differences from an inclusive education perspective. Methods: A systematic review with meta-analysis was conducted following PRISMA guidelines and registered in PROSPERO. Observational studies comparing physical fitness between children and adolescents with hearing loss and their hearing peers were included. Methodological quality was assessed using the Newcastle--Ottawa Scale, and standardized effect sizes were calculated with a random-effects model. Results: Five studies (n=404) were analyzed. Findings revealed significant differences in strength, agility, speed, and balance. Moreover, the meta-analysis showed a large standardized effect favoring hearing children (ES=-2.35; 95% CI: -3.34 to -1.37). Conclusions: Children and adolescents with hearing loss present significantly lower physical fitness, which may affect the planning of physical education activities if their capacities are misinterpreted. Implementing inclusive and adapted strategies within the school curriculum is essential to ensure equal opportunities, improve physical fitness, and promote educational equity.

Background: Individuals with attention-deficit hyperactivity disorder (ADHD) are at increased risk for cannabis misuse, with increasing prevalence among young adults. Existing evidence suggests that cannabis can have therapeutic effects on ADHD symptoms, and continued use may be partly driven by perceived improvements in symptom-related deficits. To investigate the neural evidence for these associations, we integrated functional neuroimaging and Allen Human Brain Atlas transcriptomic data to assess neural correlates of ADHD in regions targeted by cannabinoids as predictors of cannabis use. We hypothesized that greater ADHD symptoms would lead to higher cannabis use frequency through associations of ADHD symptoms with functional deficits in cannabinoid receptor type 1 (CB1R; encoded by the CNR1 gene) expressing brain regions. Methods: We tested 466 college students (ages 18-19) with varying ADHD symptom severity and cannabis use, self-reported at baseline and three yearly-follow up questionnaires. ADHD-related neural deficits were tested in a subset of 144 participants using an fMRI stop-signal task at baseline. Growth mixture modelling categorized participants with similar cannabis use into three latent classes. The covariance between the CNR1 gene expression map and differences in stop-signal task activation were tested as a mediator linking ADHD symptoms and cannabis use. Results: Greater ADHD symptoms significantly predicted reduced activation within CNR1-expressing regions, which predicted higher-use cannabis class membership. Conclusions: Our results add support for the self-medication hypothesis for higher rates of cannabis use among individuals with greater ADHD symptoms, which may be mechanistically linked through CB1R-enriched attention and inhibitory networks, highlighting neural targets for prevention and treatment.

The availability of hearing aids that can connect wirelessly to smartphone technologies via Bluetooth has grown exponentially in recent years. However, there is limited evidence assessing the benefits of user-adjustability afforded by these devices. This study aimed to assess the benefits of smartphone-connected hearing aids and an accompanying application (or app) in new and existing hearing aid users. In this single-centre, prospective, observational study, 44 adult hearing aid users (14 new and 30 existing) were recruited. Participants were fitted bilaterally with smartphone-connected hearing aids that could be adjusted by the user via an app. Self-reported outcome measures were collected at fitting and after seven-weeks of using the device in everyday life. For both new and existing hearing aid users, significant improvements in social participation, hearing-related fatigue, and hearing aid benefit and satisfaction were found. For existing hearing aid users, all outcomes were significantly better for the smartphone-connected hearing aids plus app in comparison to their existing hearing aids that did not connect to a smartphone, all with moderate-to-large clinical effect sizes (d> .6). User-controllability via the app was identified as the key benefit, and most participants (68%) reported that the app met their needs 'extremely' or 'very well'. These results suggest that, when used in conjunction with an app, smartphone-connected hearing aids can improve hearing outcomes due to greater user-controllability to improve listening. Thus, smartphone-connected hearing aids have the potential to facilitate patient-centred care, empowering the individual to successfully manage their hearing loss.

This tutorial seeks to facilitate the use of mobile electroencephalography (EEG) in young children. Mobile EEG allows researchers to investigate neural correlates of behavioral and cognitive processes in ecologically valid settings. While mobile EEG has been widely adopted in adult research, studies applying it to freely moving children remain scarce. However, investigating neural processes during active behavior and in interaction with movement is indispensable for advancing our understanding of neural correlates of cognitive development in early childhood. Here, we provide a practical tutorial on the collection and preprocessing of mobile EEG data from children. Drawing on experience and data from a large-scale study with toddlers, we summarize key methodological considerations, discuss common challenges and practical recommendations, and present a preprocessing pipeline developed for developmental mobile EEG data. In addition, we provide example EEG datasets from naturally moving 18-20-month-old toddlers. We argue that incorporating mobile EEG into developmental cognitive neuroscience allows researchers to (i) investigate cognitive development in naturalistic environments, (ii) examine associations among bodily movement, neural activity, and behavior, and (iii) study samples that are difficult to reach with stationary research. HighlightsO_LIMobile EEG enables investigation of neural processes during active behavior C_LIO_LIMobile EEG in moving freely children comes with unique methodological challenges C_LIO_LIWe provide practical recommendations for developmental mobile EEG studies C_LIO_LIA dataset and preprocessing pipeline from a toddler mobile EEG study are provided C_LI

Background: Transcranial direct current stimulation (tDCS) is increasingly used as an adjunct to rehabilitation for young people with cerebral palsy (CP), yet considerable variability exists in clinical response. Individualised electric field modelling provides an opportunity to estimate the distribution of electrical fields generated by the stimulation delivered to the brain and explore potential relationships with functional outcomes. Methods: Structural MRI scans from nineteen participants (10-16 years) from a previously published randomised controlled trial (ISRCTN74235136) investigating the effects of tDCS combined with motor training, underwent participant-specific finite element modelling using SimNIBS. Electric field strength was quantified within anatomically defined motor regions of interest, including the primary motor cortex (M1), dorsal premotor cortex (PMd), supplementary motor area (SMA), and a combined motor network. Global grey matter electric field metrics and stimulation focality were also extracted. Results: Estimated electric field strength differed significantly across motor regions (p<0.001), with PMd receiving significantly greater stimulation than both M1 and SMA. Electric field strength within a control region (primary visual cortex) was significantly lower than within M1 (p<0.001). Despite inter-individual variability in regional and global electric field metrics, no significant associations were observed between estimated electric field strength or focality and changes in function following intervention. Conclusion: Individualised electric field modelling demonstrated that an M1-targeted tDCS montage preferentially stimulated PMd rather than M1 in young people with CP. These findings highlight the importance of subject-specific modelling when characterising current distribution and suggest that variability in electric field strength alone does not explain variability in behavioural response.

In conventional hearing-aid personalisation, clinicians cannot hear what their patients hear, and patients cannot often reliably detect or describe what they hear. Self-adjustment avoids this issue but requires user controls that adjust hearing-aid signal processing parameters to be effective, efficient and easy. In this study, we explored (a) the roles of interface complexity and stimulus type in the self-adjustment of hearing-aid gain, and (b) how well individuals can adjust one sound to match another to assess the same interfaces and stimuli. Adult hearing-aid users with mild to moderate symmetrical sensorineural hearing loss repeatedly adjusted the gain (a) to their preference from individual prescription (n = 41) and (b) to match their previous preferences from a random starting point (n = 32) using three interfaces representing different bass/mid/treble configurations and three stimuli (music, speech and speech-in-noise). The large interindividual variability in self-adjusted gains clustered into three patterns of deviation from initial prescription: increased relative bass, overall gain reduction, and close to initial prescription. There were no substantial effects of interface nor stimulus on self-adjustment reliability (median {sigma} = 2.8 dB), whereas absolute sound-matching error increased with increasing interface complexity and centre frequency. Neither individual matching accuracy nor questionnaire responses predicted either self-adjusted gains or reliability. Overall, these results show that many - but not all - hearing-aid users can adjust gains with reasonable reliability, and while it can be difficult to predict the behaviour from the individual, the individual applies a similar self-adjustment behaviour across different interfaces and stimuli.

The subiculum (SUB) is a major hippocampal output hub that routes information to cortical and subcortical targets, and its long-range projections are considered excitatory. Using enhancer-driven adeno-associated viral vectors to selectively label {gamma}-aminobutyric acid (GABA)-releasing neurons across species, here we show that the dorsal SUB also sends an inhibitory projection to the dorsal part of the medial entorhinal cortex (MEC) in mice and rats. Anterograde tracing in mice revealed that the dorsal SUB contains GABAergic neurons that project sparsely to all layers of the dorsal MEC with enrichment in superficial layers, in contrast to the glutamatergic SUB axons targeting MEC layer V. Slice electrophysiology demonstrated that these GABAergic axons form inhibitory synapses in the MEC. A subset of projecting neurons expressed parvalbumin (PV), whereas somatostatin-positive neurons were rare. Consistently, PV neuron-specific anterograde tracing recapitulated the SUB-to-MEC projection. In rats, subicular GABAergic axons were enriched in MEC layer II, and SynaptoTAG2-labeled presynaptic boutons were positive for the vesicular GABA transporter, supporting inhibitory synapse formation. Anterograde tracing of PV neurons similarly recapitulated the laminar axonal distribution in the MEC. These results identify a conserved PV-associated inhibitory SUB-to-MEC projection with species-specific laminar organization, extending the canonical excitatory view of subicular output.

Drosophila s-LNv clock neurons promote nighttime sleep by releasing the neuropeptide sNPF to activate sNPF receptors (sNPF-Rs) on l-LNv clock neurons. Behavior is controlled by synaptic transmission, but s-LNv and l-LNv neurons are not connected directly by chemical synapses. To investigate the basis of sNPF/sNPF-R communication between LNv neurons, the spread of sNPF was imaged in the adult brain. We report the daily midmorning burst of sNPF released from s-LNv terminals does not reach l-LNv neurons or s-LNv somata. Instead, sNPF released by the s-LNv soma late at night in response to sleep-promoting IP3 signaling reaches l-LNv somata, but not their terminals. In addition to communication by neuropeptide diffusion, analysis of fly connectomes revealed that adult s-LNv and l-LNv neurons form non-synaptic direct contacts mediated by cytonemes. Remarkably, genetically perturbing LNv neuron cytonemes alters sleep latency, but not nighttime sleep, the target of somatic sNPF release, or circadian behavior, which depends on PDF neuropeptide released by LNv terminals. Therefore, three distinct aspects of adult rhythmic behavior are produced by terminals, the soma and cytonemes, with the latter possibly acting via contacts that are not currently annotated in the connectome.

Objective: To evaluate the efficacy, engagement, and usability of Tune Out, an unguided, self-paced online tinnitus management program, for reducing tinnitus severity in adults with tinnitus. Design: A two-arm, parallel-group randomised controlled trial was conducted with Australian adults reporting diagnosed or self-reported tinnitus. Participants were randomised to immediate access to Tune Out or a waitlist control group. Outcomes were assessed at baseline, 6 weeks, and 12 weeks. The primary outcome was tinnitus severity measured using the Tinnitus Functional Index (TFI). Secondary outcomes included tinnitus handicap, psychological symptoms, program engagement, self-efficacy, and usability. Results: Eighty-eight participants were randomised: 43 to the intervention group and 45 to the waitlist control group. The primary outcome analysis included 63 participants at 12 weeks. A significant Group x Time interaction was observed for TFI total score, indicating greater reductions in tinnitus severity over time in the intervention group compared with waitlist control, F(2, 102.57) = 5.95, p = .004, partial 2= .104. Significant effects were also observed for tinnitus handicap, F(2, 106.76) = 4.12, p = .019, partial 2 = .072. Effects on psychological symptoms were less consistent, although anxiety showed a significant Group x Time interaction, F(2, 116.85) = 3.63, p = .030, partial 2 = .059. At 12 weeks, 23.1% of intervention participants achieved a clinically meaningful reduction in tinnitus severity compared with 5.4% of controls. Program use was highly variable, with a median use of 1.10 hours, and 25.6% of intervention participants recording no use. Usability ratings were favourable among respondents, with a mean System Usability Scale score of 73.13. Conclusions: Tune Out demonstrated preliminary efficacy for reducing tinnitus severity and tinnitus handicap compared with waitlist control. Effects on broader psychological symptoms were less consistent. Although usability was rated positively, low and variable engagement highlights the need for strategies to support uptake and sustained use in unguided digital tinnitus interventions.

Aims: To assess whether recent declines in U.S. rolling 12-month-ending drug overdose death counts are projected to continue, compare the retrospective performance of short-term forecasting models, and estimate national and regional 12-month changes. Design: Comparative time-series forecasting study with a retrospective March 2025-February 2026 forecast evaluation and subsequent 12-month-ahead projections through February 2027. Setting: United States and four U.S. Census regions: Northeast, Midwest, South, and West. Cases: Aggregate drug overdose deaths reported in the National Center for Health Statistics Vital Statistics Rapid Release system (VSRR) and identified using ICD-10 underlying cause-of-death codes X40-X44, X60-X64, X85, and Y10-Y14. Measurements: The primary outcome was the monthly series of rolling 12-month-ending overdose deaths. Candidate models included ARIMA, generalized additive models, Prophet, and AICc-ranked n-sub-epidemic models. Models were calibrated using January 2020-February 2025 data and evaluated against March 2025-February 2026 observations using mean absolute error, mean squared error, empirical 95% prediction interval coverage, and weighted interval score (WIS). Individual models were ranked by retrospective WIS, and normalized inverse-WIS weights were used to construct ensembles from the top-ranked models. Final forecasts were generated for March 2026-February 2027 after recalibrating models using January 2020-February 2026 data. Results: Retrospective WIS performance differed geographically: GAM performed best nationally and in the Midwest and West, the leading n-sub-epidemic model in the Northeast, and ARIMA in the South. Median forecasts from all individual models and ensembles projected declines from February 2026 to February 2027 nationally and in each region, although prediction intervals varied substantially. Individual national median projections ranged from declines of 12.8% to 25.8%, while weighted-ensemble median projections indicated declines of 20.5% to 21.7%. Projected weighted-ensemble declines were larger in the Northeast (25.4%-30.0%) and Midwest (24.3%-26.3%) than in the South (16.6%-19.5%) and West (18.0%-21.8%). Summary: Ensemble forecasts of the reported provisional VSRR series were consistent with continued declines in rolling annual overdose death counts nationally and across U.S. Census regions. The projected magnitude of decline differed by region and model specification. Because the forecasts used provisional rolling 12-month-ending counts, they should be interpreted as surveillance projections rather than exact monthly mortality predictions.

Parkinsons disease is predominantly characterized by dopaminergic neurodegeneration linked to toxic aggregation of -synuclein. Genipin, a bioactive iridoid, was previously shown to improve the motility and survival deficits caused by pan-neuronal expression of native -synuclein in a transgenic Drosophila melanogaster model system. We show that expression of -synuclein causes sleep deficits and that genipin treatment rescued these sleep deficits, increasing total sleep and consolidating nighttime sleep relative to untreated -synuclein-expressing fruit flies. Our findings extend genipins protective profile in Drosophila melanogaster and highlight sleep regulation as an additional phenotype responsive to -synuclein-targeted interventions.

Aims: To evaluate whether Cue-Induced Retrieval and Reconsolidation with Episodic Future Thinking (CIREF), which combines personalized drug-cue retrieval with structured future-oriented processing, produces greater changes in craving and delay discounting than a recent-past episodic active control in individuals with opioid use disorder receiving methadone maintenance treatment. Design: Multicentre, two-arm, parallel-group randomized controlled pilot trial with per-protocol analyses. Setting: Two outpatient addiction treatment and rehabilitation centres in Tehran, Iran. Participants: Thirty participants with opioid use disorder receiving methadone maintenance treatment were randomized to CIREF or Episodic Recent Thinking (ERT; n = 15 per group). Twenty-eight completed the intervention and were included in the analyses (n = 14 per group). Intervention and comparator: Participants completed one screening, baseline, and personalized cue-development session followed by three 75-minute intervention sessions. CIREF combined personalized drug-cue retrieval with future-oriented simulation, prediction, intention, and planning. ERT was structurally matched but anchored episodic processing to the recent past. Measurements: Primary craving outcomes comprised the three Desire for Drug Questionnaire (DDQ) subscales assessing session-level phasic/current craving immediately before and after each intervention session and the four Obsessive-Compulsive Drug Use Scale (OCDUS) subscales assessing tonic craving before and after the intervention period. The secondary outcome was Monetary Choice Questionnaire (MCQ) log(k), with more negative values indicating less steep delay discounting. Findings: After Holm correction across the three DDQ subscales, Group x Occasion interactions indicated greater reductions with CIREF for Desire and Intention to Drug Use, FGG(1.23, 32.09) = 24.37, pHolm < .001, partial eta-squared = .484, and Negative Reinforcement, FGG(1.35, 35.23) = 17.67, pHolm < .001, partial eta-squared = .405, but not Drug Abuse Control (pHolm = .172). After Holm correction across the four OCDUS subscales, only Desire and Mental Preoccupation with Drugs showed a significant Group x Time interaction, F(1, 26) = 12.35, pHolm = .007, partial eta-squared = .322; the remaining subscales were not significant (adjusted ps >= .177). MCQ log(k) showed a Group x Time interaction, F(1, 26) = 7.18, p = .013, partial eta-squared = .217; mean log(k) changed from -1.22 (0.36) to -1.80 (0.55) in CIREF and from -1.39 (0.32) to -1.44 (0.44) in ERT. Conclusions: In this small pilot sample, the future-oriented retrieval-based intervention produced greater changes than the recent-past active control in two dimensions of session-level phasic craving, one dimension of tonic craving, and monetary delay discounting. The results are preliminary and do not establish memory reconsolidation or effects on relapse or longer-term clinical outcomes.

Early postnatal development is a critical period for hippocampal circuit maturation. While postnatal hippocampal development has been mostly studied in rats, less is known about the developmental trajectory of electrophysiological properties in mice, despite the wide use of these animal models for molecular and genetic studies of nervous system. In this study, we investigated the postnatal maturation of hippocampal CA1 pyramidal neurons in male and female wild-type mice. Whole-cell patch-clamp recordings were performed in acute hippocampal slices to assess passive and active membrane properties as well as spontaneous excitatory synaptic activity. We found that maturation of neuronal firing properties was associated with faster responses to stimulation, higher-amplitude and shorter-duration action potentials, and more precise control of neuronal firing. Simultaneously, synaptic activity changed across development, with decreased sEPSC inter-event intervals and stable event amplitudes, suggesting enhanced functional connectivity without major changes in synaptic strength. Sex-dependent differences in electrophysiological properties were observed primarily during the first postnatal week, indicating that sex influences the early trajectory of neuronal maturation. Together, our findings provide a comprehensive electrophysiological baseline for mouse hippocampal CA1 pyramidal neurons during postnatal development.

Intergroup conflict is one of the most significant issues in human society. In the 1950s, Sherif et al. reported that intergroup conflict could be artificially induced in boys through intergroup competition with tug-of-war and ball games. Since this iconic study, researchers have developed various experimental methods to replicate intergroup competition and/or conflicts. However, although intergroup conflicts in wild animals are often reported, it has been difficult to establish a situation of intergroup conflict in laboratory rodents that is discriminable from aggressive behavior individually. In this study, we established a novel experimental paradigm for intergroup competition in mice in which the members of each group shared objectives and tasks. Adult male ICR/Jcl mice were housed in groups of six, divided into two teams of three and repeatedly performed a competitive Tsunahiki task (tsunahiki means tug-of-war in Japanese). The competitive Tsunahiki task was conducted in an open field divided into two experimental fields, with three ropes stuck to a wall separating the fields. The mice were required to pull two ropes out faster than their opponent team to win, and only the winners could proceed to the reward area separated by a guillotine door. We demonstrated that the experience of the competitive Tsunahiki task induced attack bites selectively toward members of the other team (out-group members). Our findings suggest that intergroup competition induces intergroup conflict in mice, providing a technical breakthrough in elucidating the detailed neuroscientific mechanisms underlying intergroup conflict.

The P300 amplitude reduction, or P3AR, is a decrease in the magnitude of the P300 event-related potential (ERP) waveform, typically measured via EEG during oddball tasks, and widely observed in those diagnosed with Alcohol use Disorder (AUD). Though widely acknowledged as a biological correlate of AUD, most of the extant literature on the P3AR features conventional time-domain measurement approaches, and further, the work has predominantly focused on alcohol use specifically. In order to precisely capture the nature of this association as well as assess generalizability to other substances, the current study utilized advanced time-frequency analyses to compare P3 activity in individuals with AUD, cocaine use disorder, and comorbid alcohol and cocaine use. Time-frequency analyses indexed separable theta and delta activity underlying the conventional time-domain P3. Findings revealed that in the conventional time-domain, we observed P3AR shared across alcohol and cocaine use. These findings replicate literature suggesting P3AR associated with substance use. Within time-frequency analyses, we found broad delta reductions across substances, aligning with literature suggesting that delta is mostly comprised of the P3 ERP. For theta-band activity, we found reductions in. amplitude specific to alcohol users only, with no significant diminutions present for cocaine users. As most previous literature focused on alcohol use, unique theta modulations relative to cocaine users provides theoretical clarity in terms of the association of P3AR to substance use more broadly. The findings of the current study highlight the utility of time-frequency measurement approaches in parsing overlapping activity and indexing separable processes with relevance to substance use otherwise unaccounted for in the time domain.

TULIP (TUbular LIPid binding) domain proteins (TDPs) are found in all living organisms including bacteria. They have various documented functions, some of which clearly related to their intra- or extracellular lipid transfer activities. Extracellular, BPI-related TDPs of insects (B-TDPs, also known as Takeout-related proteins), are often found in chemosensory organs, but little is known regarding their exact location or how they could contribute to olfaction or gustation. We have surveyed and updated the full set of Drosophila B-TDPs and found that roughly 50% are overexpressed in chemosensory organs. Focusing on three genes clustered on the third chromosome, we provide evidence that at least one of the encoded proteins is secreted in the lymph cavity housing the dendrites of olfactory neurons. Biochemical data give support for a putative function of B-TDPs as odorant transporters, but loss-of-function analyses also hint to a potential role as a barrier against plant-emitted terpenoids.

Background and Aims: Anxiety remains prevalent among adolescents while tobacco and nicotine product use, especially the recent increases of novel product use such as e-cigarettes and nicotine pouches, raises further public health concerns. The associations between novel tobacco and nicotine product use and anxiety remains understudied. This study aims to determine whether tobacco and nicotine product use is associated with generalised anxiety and whether this association differs by used product. Design: Cross-sectional survey, School Health Promotion study in 2025. Setting: A school-based nationwide survey conducted in all Finnish lower and upper secondary schools. Participants: Students aged 13-20 years in three school levels: 8.-9. grade students in lower secondary schools (N= 94 743, 73% of the students), 1st and 2nd-year students in general upper secondary schools (n=47 248, 70% of the students) and of vocational institutions (n=24 998, 38% of the students). Measurements: Exclusive (single product) and non-exclusive ([&ge;]1 products) daily or weekly use of tobacco and nicotine products, including nicotine pouches, e-cigarettes, cigarettes, and smokeless tobacco (snus). Generalised anxiety was measured using the Generalised Anxiety Disorder Scale (GAD-7). The cut-off of >10 points indicated participants with moderate to severe self-reported generalised anxiety symptoms. Background variables included sociodemographic variables and heavy drinking. Results: Of the 166,989 participants 51.4% were females, mean age was 15.7 (SD 1.27), 21.2% reported generalised anxiety. Prevalence of generalised anxiety increased gradient-wise in accordance with both non-exclusive and exclusive use frequency of different tobacco and nicotine products, as well as with number of products used. Daily use of nicotine pouches was associated with higher odds of anxiety compared with never use (boys: adjusted odds ratios (aOR) 1.19, 95% CI, 1.05 to 1.34; girls: aOR 1.74, 95% CI, 1.58 to 1.91), yet the association between daily e-cigarette use seemed to be stronger (boys aOR 1.96, 95% CI, 1.54 to 2.49; girls: aOR 2.29, 95% CI, 2.09 to 2.51). Summary: Any use of tobacco and nicotine products, including new products, is associated with generalised anxiety among adolescents, with some differences between products. Measures to prevent the initiation of tobacco and nicotine product use and to promote mental health among adolescents should be enacted.

Objective: Impaired understanding of noisy or degraded speech is a central feature of listening difficulties (LiD), but the possible causes of these symptoms are wide-ranging. Accordingly, recent research underscores the need to study these deficits using a test battery approach. Event-related potentials are useful objective metrics for studying LiD, but probing function across the speech processing hierarchy using traditional protocols is sequential and unrealistic in clinical settings. The novel chirped speech (Cheech) method combines natural speech with acoustic chirps to overcome these limitations. This study examines its utility for profiling childhood LiD. Methods: Twenty-eight children (15 typically developing, 13 with LiD), aged 8-17 years old, listened to a 17-minute Cheech story and detected a target word within the story via button press while EEG data were collected from 53 scalp sites. Results: Cheech successfully evoked responses from the auditory brainstem response through to the brain's language centers, as reflected by the N400 effect. Unlike TD children, those with LiD demonstrated N400 effects with atypical distributions that favored frontal rather than the typical parietal sites. A trend towards a delayed and reduced amplitude Wave V was also observed. Conclusions: Hierarchical examination of speech processing using Cheech primarily implicates altered language processing as a contributing factor to LiD, with the frontal topography of the N400 effect for those with LiD potentially suggesting a greater reliance on deliberate memory retrieval during the speech perception task. Significance: LiD could arise due to auditory and/or cognitive factors. The present results demonstrate the feasibility of objective, parallel measurement across this hierarchy and point to impaired language processing as a possible mechanism.

Acoustic cues such as pitch and spatial location allow listeners to attend to a target speaker and ignore competing talkers, aiding speech recognition in background noise. Diminished ability to utilize acoustic cues for speech stream segregation may thus contribute to older adults' challenges hearing in noise. Adults aged 18-74 completed a speech-in-speech identification task with three conditions containing 1) only pitch cues (fundamental frequency), 2) only spatial cues (interaural time differences; ITDs), and 3) both pitch and spatial cues for segregating a target talker from competing talkers. Hearing thresholds at standard and extended high frequencies (EHFs), auditory brainstem responses (ABRs), and digit span scores were acquired to examine the influence of sensory and cognitive factors on use of each acoustic cue for speech-in-speech recognition. Significant differences were observed between cue condition scores indicating that use of the available cue(s) drove performance. ABR metrics were not a significant predictor but digit span scores significantly predicted scores on all three cue conditions. Working memory abilities therefore set a baseline for participants' speech-in-speech recognition regardless of the acoustic content. Hearing thresholds at standard frequencies significantly predicted scores on the Pitch condition. EHF hearing thresholds better predicted Spatial and Both Cue condition performance, suggesting that EHF thresholds represent auditory processing important for coding ITDs. Age group analysis revealed that older adults (aged 40+) performed significantly more poorly on all cue conditions of the speech-in-speech recognition task relative to younger adults. Age-related changes in auditory sensory processing may therefore impair older adults' speech-in-noise perception by reducing their ability to use acoustic cues for segregating target and competing speech.