European Journal of Neuroscience

Dopamine (DA) is important in many fundamental behaviors, including positive and negative reinforcement, incentive salience, and decision-making. This behavioral diversity is now known to be due, in part, to neurotransmitter diversity, based on rodent models. To address DA neuron transmitter properties in higher species, we examined the ventral midbrain in 5 young macaques (3 male, 2 females, 3-6 years) using RNAscope in situ hybridization for tyrosine hydroxylase (TH), vesicular glutamate transporter 2 (VGluT2) and glutamic acid dehydroxylase 1 (GAD1) across the A10 (VTA; midline VTA nuclei and parabrachial nucleus; PBP), the A9 (substantia nigra, pars compact, SNc) and the A8 (retrorubral field, RRF) subregions. We followed up with immunocytochemical studies in the same cohort to infer extent of mRNA and protein matches. There were 7 mRNA phenotypes, with TH-mRNA containing cells forming the largest proportions of all neurons, as expected. Surprisingly, multiplexed TH+ neurons were much more frequent than TH-single labeled neurons overall (TH-VGluT2, 22% and TH-VGluT2-GAD1, 23% compared to TH-single labeled neurons, 19%). GAD1 mRNA co-expression mainly occurred in triple labeled cells, i.e. those with VGluT2- and TH mRNA expression. VGluT2 mRNA single-labeled neurons represented only 8%, and GAD1 mRNA single-labeled neurons comprised 20%, of the total population. Proportions of cellular phenotypes were similar across the A10-A9-A8 subregions. Most DA neurons in the young macaque contain multiple transmitters, indicating an important role for fast synaptic transmission alongside dopaminergic transmission in all subregions. We discuss the developmental and circuit implications of these findings in higher primates.

Apuschkin et al. (2024) proposed a GPCR-based transcriptomic atlas for midbrain dopamine (DA) neuron subpopulations, including candidates such as Nmur1, Cckar, and Ffar4. To guide genetic targeting, these markers must reflect functional expression in adult DA neurons. Using in situ hybridization, Cre-dependent reporter lines, and both intracranial and systemic viral approaches, we find no evidence of adult Nmur1-mediated recombination in DA neurons, while Cckar-driven recombination is consistent with developmental expression only. Notably, Ffar4 expression overlaps extensively with Ntsr1 midbrain populations, indicating that it does not define a distinct DA neuron class. Furthermore, analysis of independent spatial transcriptomic datasets together with our MERFISH data shows that many proposed GPCR markers are not detectably expressed in adult DA neurons. These findings demonstrate that transcriptomic enrichment does not always yield reliable adult markers and highlight the need for functional validation prior to use in circuit targeting.

Objective: Cross-sectional studies indicate associations between self-reported social media use and adolescent wellbeing outcomes. We aimed to evaluate longitudinal associations of objectively measured smartphone and social media use with psychosocial wellbeing. Design: Observational study with one year of follow-up Setting: High schools in Finland from 2022 to 2023 Population: 259 adolescent girls (mean age 16.3 years at baseline) Main outcome measures: screenshots depicting smartphone and social media use, Bergen Social Media Addiction Scale (BSMAS), Generalized Anxiety Disorder-7 questionnaire, Body Appreciation Scale 2 (BAS-2) and visual analogue scales (VAS) of mood, tiredness, and loneliness Results: Across one year of follow-up, anxiety, body appreciation, and mood improved, but possible social media addiction increased from 15% to 17%. Social media addiction at baseline was associated with increased anxiety (r=0.29, p<0.001), lower body appreciation (r=-0.15, p=0.022), and more loneliness (r=0.20, p=0.001) at follow-up. Anxiety at baseline was associated with social media addiction at follow-up (r=0.19, p=0.005). The highest quartile of TikTok users reported more social media addiction (BSMAS 19 [IQR 16-21] vs. 17 [IQR 14-20]; p=0.009) and lower body appreciation (BAS-2 32 [IQR 28-38] vs. 35 [IQR 29-40]; p=0.003) than did others. The highest quartile of Snapchat users reported more social media addiction (BSMAS 19 [IQR 15-21] vs. 17 [IQR 14-20]; p=0.007) and tiredness (VAS 21 [IQR 13-32] vs. 26 [IQR 15-35]; p=0.049) than did others. Conclusions: Consistent with cross-sectional studies, social media addiction was associated with poorer psychosocial outcomes across follow-up. Policies to protect adolescents from social media addiction are urgently needed.

Tourette syndrome (TS) is a neurodevelopmental disorder of childhood onset characterised by vocal and motor tics and is associated with cortical-striatal-thalamic-cortical circuit [CSTC] dysfunction. TS often follows a developmental time course in which tics become increasingly more controlled during adolescence. However, many individuals continue to have debilitating tics into adulthood. This indicates that there may be important differences between adults with TS for whom the clinical phenotype is more stable, and children and adolescents with the disorder who may be undergoing developmental neuroplastic changes linked to the reduction of their tics. Previous studies have used transcranial magnetic stimulation (TMS) to investigate changes in cortical motor excitability in individuals with TS, including measurement of resting motor threshold (RMT). However, the findings from these studies have been mixed, have varied between adult and child samples, and have often been based on small sample sizes. Here we report a multi-centre, mega-analytic, study in which RMT data collected from children and adults with TS at multiple research centres was pooled for analysis. Results confirmed that mean RMT was significantly increased in individuals with TS compared to neurotypical controls. However, this result can be explained by the more important findings that: (a) RMT for adults with TS did not differ from that of neurotypical adults; and (b) the rate that RMT decreases with age during childhood and adolescence is reduced in individuals with TS compared to controls. Thus, while neurotypical individuals reach an adult RMT level by ~12-13 years of age, individuals with TS are substantially delayed in doing so, and do not reach an adult RMT level until much later, at ~24 years of age. We conclude therefore that differences in measures of cortical excitability between children and adolescents with TS and chronologically age-matched neurotypical controls may likely reflect a developmental delay in the maturation of functional brain networks in individuals with TS, which may normalise with age.

BackgroundElectroencephalographic (EEG) studies attempting to characterise the neural signature of meditation typically rely on contrasts with passive rest or comparisons among practitioners based on experience. However, these approaches rarely include active control states and seldom establish the reliability and robustness of identified quantitative EEG features. Consequently, the validity of proposed neurophysiological markers of meditative state remains uncertain. The present study addressed these limitations by using a reliability-informed, multi-session within-subject design to characterise distinct state-dependent EEG dynamics in experienced meditators from the Brahmakumaris Rajayoga tradition. MethodsThirty long-term meditators underwent repeated EEG recordings over two days, comprising two meditation sessions per day. Each meditation block was flanked by rest periods, with a cognitive task between sessions to reduce carryover effects. We quantified broadband spectral power, aperiodic slope and intercept, and nonlinear dynamical measures, including detrended fluctuation analysis (DFA), Higuchi fractal dimension, and permutation entropy (PE), across meditation, rest, and task conditions. ResultsCompared with both rest and task states, meditation was associated with increased theta-alpha power, an elevated aperiodic intercept, and systematic modulation of nonlinear indices (DFA, Higuchi, PE). Further meditative core features demonstrated high inter-session test-retest reliability, strong inter-individual consistency, stability across guided and silent meditation states, and were not moderated by years of meditative experience. ConclusionThe present framework identifies a reproducible neurodynamic core of meditation, distinct from passive and active control states, spanning spectral, aperiodic, and nonlinear EEG domains in long-term meditators. These findings enhance the construct validity and measurement reliability of meditation-specific neural markers.

BackgroundTheta-frequency transcranial alternating current stimulation (tACS) over prefrontal cortex has been proposed to modulate working memory (WM), yet behavioral effects are often inconsistent. One potential source of variability is the tACS phase during stimulus presentation. ObjectiveWe tested whether behavioral performance during WM depends on the phase of prefrontal theta-tACS. MethodsTwenty participants completed two sessions of prefrontal 4 Hz tACS in a within-subject design, receiving active and sham stimulation in separate sessions. Participants performed a visuospatial change detection task (CDT) and a verbal N-back task. Stimulation effects on overall accuracy and reaction time were analyzed. Subsequently, phase-specific analyses related stimulation phase at task-relevant stimulus presentation to behavioral performance using circular regression models. Preferred phases across participants were tested using Rayleigh tests. ResultsNo significant overall effects of active compared with sham tACS on accuracy or reaction time were observed in either task. However, phase-specific analyses revealed stronger phase-dependent modulation of reaction time during active tACS compared with sham. In the CDT, this effect was present across difficulty levels, whereas in the N-back task it was observed only in the 3-back condition. No reliable phase-dependent effects were observed for accuracy. Preferred phases varied across participants and did not cluster around a common phase. ConclusionsPrefrontal theta-tACS can modulate WM performance in a phase-dependent manner even in the absence of average behavioral effects. The observation of phase-dependent reaction-time modulation across visuospatial and verbal WM tasks suggests that stimulation phase may be a relevant source of variability across cognitive domains.

Social behavior is a fundamental phenotype across vertebrates. Zebrafish (Danio rerio) have emerged as a valuable translational model for investigating the neurobiological mechanisms underlying sociability, particularly due to their robust shoaling behavior and experimental tractability. However, the literature presents issues of reproducibility and inconsistent findings regarding the modulation of social preference and shoal cohesion in adult zebrafish. We conducted a systematic review and meta-analysis to synthesize studies evaluating the effects of pharmacological interventions that modulate the central nervous system and stress-related interventions on social behavior in adult zebrafish and, when available, anxiety-like behavior. The literature search was performed in three databases (Embase, PubMed, and Web of Science), followed by a two-step screening process based on inclusion/exclusion criteria. The included studies underwent extraction of qualitative and quantitative data, as well as risk of bias assessment. Interventions from the included studies (n = 108) were categorized according to their nature, mechanism of action, and/or therapeutic purpose, resulting in seven, four, and five meta-analyses for social preference, shoal cohesion, and anxiety-related tests, respectively. Ethanol, NMDA antagonists, pro-dopaminergic agents, and stress-related interventions decreased social preference, while stress-related interventions increased shoal cohesion. The fact that stress produced opposite effects suggests that these paradigms measure distinct sociability constructs, or perhaps are differentially modulated by confounding factors, like anxiety for example. The studies presented high heterogeneity, with prediction intervals compatible with effects in both directions, as well as methodological limitations and deficiencies in data reporting, as evidenced by the risk of bias assessment. These findings emphasize the need for well-designed new studies to validate the findings and expand the evidence on interventions that currently lack sufficient studies for quantitative synthesis.

Although language acquisition delays are frequently observed in children with autism spectrum disorder (autism), our current understanding of the neurobiological mechanisms underlying language development in autism is sparse. Previous studies have found resting-state electroencephalography (EEG) power to be associated with language abilities in autistic children. However, longitudinal studies examining resting-state EEG phase coherence in relation to language development in preschool-aged children with autism are limited. This study aimed to characterize age- and group-related changes in whole-brain coherence in neurotypical children and in autistic children with and without language delay. Resting-state EEG and language data were collected at 2, 3, and 4 years of age. Peak phase coherence within the alpha band (6-11 Hz) was calculated at each timepoint and differences in the developmental trajectory of peak alpha coherence (PAC) were analyzed. In neurotypical children, PAC increased between 2 and 4 years of age. In contrast, PAC did not significantly change with age in children with autism. However, when examining autistic children based on language delay status, PAC increased with age in autistic children without language delay, but not in children with language delay. Exploratory analysis revealed evidence for an interaction between PAC and age, suggesting that the direction of the association between PAC and VDQ varied across age. Overall, these results support previous findings of altered oscillatory connectivity in autism and suggest that differences become apparent early in development. Importantly, phase coherence may not only differentiate diagnostic groups but also capture meaningful variability within the autism group. Future research should further investigate the use of EEG coherence as a biomarker of language development in autism.

Background: Despite the significant risks associated with online substance procurement (SP), few researchers have examined this practice in U.S. youth. The studies that do exist are cross-sectional and cannot temporally connect specific digital behaviors to online SP. This longitudinal cohort study examined youth SP and digital media habits to determine whether use of certain smartphone applications correlated with increased odds of online SP or being contacted online about procuring drugs or alcohol. Methods: A cohort of U.S. youth (aged 15-20) with a history of non-daily substance use in the 3 months prior to enrollment was recruited to use the digital phenotyping smartphone application EARS for 90 days. On a nightly basis, participants were asked to complete surveys about online experiences related to SP and instances of substance use. Smartphone-generated screen use data were also collected passively each day. Results: Out of 112 enrolled participants, 106 were able to be included in analyses. Over approximately 3 months, 28.3% of participants (n=30) reported a collective 91 instances where they used social media to acquire drugs or alcohol. Screen use data demonstrated temporal relationships between social media SP and applications previously connected to the social media drug-purchasing process (e.g., TikTok, encrypted apps), as well as other school-specific social media. Discussion: Our results provide critically needed research evidence to support a body of literature composed predominantly of anecdotal reports. Despite measures taken by social media companies to prevent use of their platforms for drug procurement, underage youth continue to engage in this practice.

RationaleCholinergic signalling is critical for attentional control and signal detection, yet the contribution of specific acetylcholine receptor (AChR) subtypes remains poorly understood. Although the 7 nicotinic AChR (nAChR) holds promise as a target for cognition-enhancing therapy, clinical findings to date have been inconsistent. ObjectiveTo investigate the effects of putative cognitive enhancing drugs, including those targeting cholinergic transmission and 7 nAChRs on a visual signal detection task (SDT). MethodsMale and female Sprague Dawley rats were trained on an SDT. Cholinergic transmission was probed systemically with nicotinic and muscarinic receptor antagonists (mecamylamine and scopolamine), a cholinesterase inhibitor (galantamine), an M4-AChR positive allosteric modulator (PAM; VU0467154), an 7 nAChR antagonist (MLA), an 7 nAChR PAM (CCMI), and an 7 nAChR partial agonist (SSR-180,711). Dopaminergic transmission was probed using the catechol-O-methyltransferase (COMT) inhibitor, tolcapone. A novel, trial-level signal detection theory-based generalised linear mixed-effects model (SDT-GLMM) was used to index response bias and perceptual sensitivity (d'), the latter reflecting subjects ability to discriminate signal from noise. ResultsMecamylamine profoundly impaired SDT performance across all measures. Galantamine significantly improved d' at moderate doses but not when a distractor was present. MLA uniquely produced dose-dependent improvements in d' that were preserved under distraction. In contrast, positive allosteric modulation and agonism of 7 nAChRs impaired task performance. Scopolamine, VU0467154, and tolcapone had no consistent or interpretable effects on signal detection. ConclusionsThis work demonstrates that 7 nAChR modulation bidirectionally and dose-dependently regulates perceptual sensitivity, irrespective of attentional distraction. These findings have implications for targeted cognitive enhancement in disorders of attention.

Mind-wandering (MW) is a frequent and pervasive phenomenon, yet it is commonly assessed using self-reports or probe-based methods that offer limited temporal precision regarding its onset. In this study, we introduce a novel paradigm, ReMind, that estimates the onset and duration of MW episodes during natural reading by combining retrospective self-reports with eye-tracking. Participants indicated the words where they believed their mind started and stopped wandering, and these reports were aligned with gaze timestamps to estimate MW onset. Using data from 44 participants, we examined whether knowledge of MW onset improves the detection of MW from eye-tracking signals. To evaluate relevance for both self-report and thought-probe paradigms, we additionally simulated thought probes by randomly sampling time points during reading. Logistic regression classifiers trained on eye-tracking features extracted from time windows anchored to MW onset achieved AUROC scores of 0.659 and 0.621 under the self-report and simulated thought-probe paradigms, respectively, using leave-one-subject-out cross-validation. In both cases, onset-aligned windows outperformed classifiers trained using arbitrary MW windows. Sliding-window analyses further revealed systematic temporal changes around MW onset, with classification performance peaking at approximately 3 seconds after onset. Feature-level analyses showed reduced fixation rate and fixation dispersion, along with increased pupil size following MW onset. Together, these findings characterize the temporal progression from on-task reading to MW. Overall, ReMind provides a useful framework for studying the temporal dynamics of MW during naturalistic reading.

During social interactions, people continuously align their movements and rhythms, a process known as interpersonal synchrony that supports rapport, mutual understanding, and smooth communication. In autism spectrum disorder (ASD), previous studies have often reported atypical or reduced synchrony, but most have relied on aggregate or session-averaged measures that may miss how coordination develops over time. It therefore remains unclear whether interactional differences in autism reflect a general reduction in synchrony or altered temporal dynamics of interpersonal coordination. We examined the temporal dynamics of head-movement synchrony during a structured face-to-face communication task, comparing non-autistic dyads (two typically developing [TD] partners) with mixed-neurotype dyads (one TD speaker paired with one autistic listener), using gyroscope-based tracking and time-resolved trajectory modelling. Phase-based synchrony, indexed by the phase-locking value (PLV), was lower overall in mixed-neurotype dyads. Critically, time-resolved analyses revealed a marked group difference in synchrony trajectories: non-autistic dyads showed progressive, adaptive growth in synchrony over the interaction, whereas mixed-neurotype dyads showed a significantly attenuated, flatter pattern. These findings suggest that autism may involve altered temporal organization of social coordination rather than simply reduced synchrony overall. Lay AbstractWhen we talk with someone, we often naturally match their body language and rhythms without even realizing it. This physical "syncing up" helps us feel connected, builds trust and shared understanding, and makes communication flow easily. Research shows that autistic people might sync their movements differently during conversations compared to non-autistic people. However, past studies usually just measured an overall average of this syncing across a whole interaction. This approach misses how human interactions actually unfold over time. We wanted to know: do autistic people just sync less overall, or does their syncing change differently as the conversation goes on? To find out, we used small motion sensors to track the head movements of adults having structured face-to-face conversations and compared two types of pairs: non-autistic pairs, where both people were non-autistic, and mixed-neurotype pairs, where one non-autistic speaker talked to one autistic listener. We found a notable difference in how the two groups interacted over time. For the non-autistic pairs, the physical syncing grew progressively stronger as the conversation progressed; they progressively "tuned in" to each other. In contrast, mixed-neurotype pairs showed a flatter pattern--their level of syncing stayed relatively constant from start to finish without that same gradual build-up. These findings are important because they suggest that differences in autistic communication are not simply a "lack" or "deficit" in social coordination. Instead, autistic individuals have a distinct style of interacting--one that maintains social engagement without relying on the progressive build-up of physical syncing that non-autistic people use. Taken together, our results highlight the importance of examining how interactions evolve over time to better understand the different ways autistic and non-autistic people communicate.

Alterations in rodent self-grooming have been used to model various facets of neuropsychiatric illness. In the context of affective behavior, increases in grooming have been proposed as a sign of stress. This is because grooming has been observed to increase in close temporal proximity to stressful events. However, in other situations, stress appears to suppress grooming, complicating the utility of measuring grooming in the study of stress and mental health. Here, we show that this discrepancy can be resolved by considering time and experimental context. We found that in initial response to stress, grooming declined in proportion to stressor intensity. Moreover, stress-related cues and anxiogenic stimuli similarly suppressed grooming. Conversely, optogenetic inhibition of the amygdala in a stress-associated context decreased threat-elicited freezing, consistent with a reduction in stress, and increased grooming. These results indicate that the immediate response to stress is a suppression of grooming. However, when stressed mice were returned to their homecage environment, grooming increased. Similarly, mice increased grooming when they returned to the safe zone in an anxiety assay. Accordingly, rather than being a defensive response to signs of danger, increased grooming seems to reflect a post-stress response that occurs once animals detect the absence of danger. These findings suggest that post-stress grooming could provide a window into the neurobiology of post-stress recuperative processes.

The persistence of a left-handed minority of slightly over 10% of the population is enigmatic because it is associated with stigma, increased psychopathology, and cognitive deficits. In a community sample of 9,352 individuals (age range 8-21 years) with neurobehavioral assessments, left-handers (N=1,281, 673 male) indeed showed greater psychopathology and performed more poorly than right-handers (N=8,076, 3,839 male) on tests of executive function, memory, complex cognition, and social cognition, while excelling in motor speed. Furthermore, the variance was higher and within-individual variability (WIV) - the extent to which scores in the different domains varied within individuals - was higher in left-handers. Since low WIV indicates even distribution of abilities while high WIV reflects specialization in circumscribed areas, the finding indicates that left-handers are "neurocognitive specialists". This combination of behavioral traits could confer resilience against natural selection pressures and help explain preponderance of left-handers in highly specialized professions requiring specific talents. Our findings encourage more research on left-handers, who are currently excluded from multiple brain behavior studies.

PurposeParkinsons disease (PD) is a neurodegenerative disease that affects motor control but can also influence sensory perception. Changes in vision and proprioception are well-documented but less is known about how PD alters auditory perception, particularly perception of speech acoustic properties. The current study examined perception of speech rate and intensity in PD and the relationship of auditory perception to disease severity. MethodPeople with PD were compared to age- and hearing-matched controls using perceptual tasks focused on discrimination and learning of speech rate and intensity. For rate discrimination, speech, non-speech, and visual stimuli were included to determine whether performance differences for PD participants and controls were specific to speech. Disease severity was assessed using the MDS-Unified Parkinsons Disease Rating Scale (MDS-UPDRS) and the relationship to performance on perceptual discrimination and learning tasks was evaluated. ResultsPeople with PD performed significantly worse than controls in the rate discrimination task for all types of stimuli. There were no significant group differences for intensity discrimination. However, participants with greater PD disease severity demonstrated significantly poorer intensity discrimination accuracy. Performance on learning tasks utilizing rate and intensity manipulations did not differ between PD and control participants and was unrelated to PD disease severity. ConclusionsPeople with PD had difficulty discriminating rate differences across speech, non-speech, and visual stimuli, indicating that challenges with rate perception are not limited to speech. The relationship between intensity discrimination and disease severity suggests common dopaminergic networks between motor symptoms and auditory perception in PD.

The present study examined whether thematic reversal anomalies are processed similarly across subject and object experiencer constructions in Malayalam. Event-related brain potentials (ERPs) were recorded as 30 first-language speakers of Malayalam read transitive sentences with the two types of experiencer verbs, in which the thematic role assignment for the preceding arguments was either correct or reverse. The reversal anomaly became apparent only at the position of the experiencer verb. A linear mixed-models analysis confirmed a biphasic N400-P600 effect at the verb for both verb types when the argument roles were reverse. Thus, our results suggest a uniform processing strategy for TRAs irrespective of the type of experiencer verb involved. However, the N400 amplitude was larger for the object experiencer verb compared to subject experiencer verbs. We suggest that the quantitative difference observed for object experiencer verbs is due to the inverse linking of grammatical function and thematic roles associated with these verbs. In other words, verb-specific linking properties modulate the processing of TRAs involving object experiencer verbs. We argue that this modulation occurs because the parser recalibrates cue weighting when the expected form-to-meaning mappings are overridden by the inverse linking properties of object experiencer verbs.

Apathy is characterized by reduced motivation for goal-directed behaviour and may emerge following brain injury. Currently, little is known about apathy in children and adolescents with neurodevelopmental disorders (NDDs) exposed to repetitive head impacts. This exploratory study investigated associations between apathy, repetitive head-banging behaviour, and substantia nigra neuromelanin-sensitive MRI (NM-MRI) signal in youth with NDDs. Forty-seven participants (14 typically developing; 33 ADHD/ASD) completed Behaviour Assessment System for Children (BASC-3) measures, from which apathy-related items were harmonized across developmental forms and subjected to principal component analysis. A one-component solution explained 47.3% of variance and was used to derive apathy scores. Although head-banging severity and NM-MRI signal were not independently associated with apathy, a significant interaction emerged, whereby greater head-banging severity strengthened the relationship between apathy and substantia nigra NM-MRI signal. These preliminary findings suggest repetitive self-injurious head impacts may influence dopaminergic systems linked to motivational dysfunction in youth with NDDs.

Meditation has been associated with improvements in attention, emotional regulation, and mental well-being, motivating increasing interest in objective methods for assessing meditative states. In this study, we investigate whether EEG-based machine learning can reliably distinguish between multiple meditation styles and mind-wandering states. EEG data were recorded from experienced meditators performing three meditation styles, Shamatha, Vipassana, and Metta, together with an eyes-closed mind-wandering condition. EEG signals were preprocessed to remove artifacts, and features were extracted from frequency, time-frequency, and time domains. Classification was evaluated using both intra-subject and inter-subject strategies with multiple machine learning classifiers. Results demonstrate high intra-subject classification accuracy across meditation-versus-mind-wandering and meditation-style comparisons, indicating strongly discriminative subject-specific neural signatures. In contrast, inter-subject performance decreased substantially, particularly for distinguishing meditation styles, suggesting considerable inter-individual variability in meditation-related EEG patterns. Furthermore, temporal analysis revealed that classification performance increase over time, indicating that the neural distinctions between meditation states become increasingly pronounced over time. Additionally, t-SNE visualization showed clear within-subject clustering but increased overlap across subjects, explaining the reduced inter-subject generalization. Overall, these findings highlight the potential of EEG-based machine learning for personalized assessment and monitoring of meditative states while emphasizing the challenges of developing subject-independent meditation classification systems.

It has been proposed that bilinguals have better executive function (EF) arising from the constant selection of one language while inhibiting the other, and gray matter has been found to differ in bilinguals in regions linked to EF (frontal-parietal and subcortical structures). Attention Deficit Hyperactivity Disorder (ADHD) is associated with poorer EF and neuroanatomical differences underlying EF. Given the EF advantage in bilinguals, we investigated whether a bilingual experience affects EF performance and brain structure differentially in those with ADHD. Using the Adolescent Brain and Cognitive Development Study, we compared early Spanish-English bilinguals and English-speaking monolinguals with and without ADHD. ANOVAs for the Flanker, Working Memory, and Card Sort Tasks revealed no main effects of Language Experience (Bilingual versus Monolingual), a main effect of Diagnostic Group for Card Sort (ADHD worse than Controls), and no interaction effects on performance for any task. ANOVAs for gray matter volume (GMV) revealed a main effect of Language Experience in many regions, a main effect of Diagnostic Group in some regions, but no interactions. GMV in left thalamus was affected by both ADHD and bilingualism, but the effect of ADHD was not significantly diminished or enhanced by the dual-language experience. For cortical thickness, there was a main effect of Language Experience in several regions, no main effect of Diagnostic Group, and no interactions. Taken together, bilingualism has some impact on EF performance, a strong impact on neuroanatomy, but there was no disproportionate impact by bilingualism on the differences caused by ADHD for any measure. Research HighlightsExecutive function and brain structure differ in ADHD and in bilinguals, prompting the need to investigate interactive effects. Bilingualism did not disproportionately affect performance differences in ADHD for executive function, nor for gray matter volume or for cortical thickness differences in ADHD. Gray matter volume was less in ADHD than non-ADHD, as well as greater in bilinguals than monolinguals in the left thalamus, but without interaction effect. These independent effects indicate that the brain basis of ADHD is not impacted by a dual-language experience.

The addictive properties of opioids are due in part to these drugs ability to alter ventral tegmental area (VTA) activity via activation of mu opioid receptors (MORs) on local and distal inputs. Prior studies have identified numerous opioid-modulated afferents to the VTA, some of which show differing levels of functional modulation by opioids, but the degree to which this parallels differences in receptor expression is not known. Hence, we used retrograde labeling combined with RNAscope to examine oprm1 mRNA expression in VTA-projecting afferents arising from a variety of distal brain regions. Because opioids are thought to be particularly influential on GABAergic afferents to the VTA, we also examined colocalization of oprm1 with GABAergic markers in VTA-projecting neurons. Interestingly, we found that oprm1 mRNA is present in both GABAergic and non-GABAergic VTA-projecting neurons. However, many (though not all) GABAergic afferents expressed higher levels of oprm1 compared to most non-GABAergic afferents (especially those arising from the cortex). These results complement previous anatomical studies that had examined oprm1 expression in these regions but in a non-quantitative way and without regard to their efferent targets. Our findings encourage future work to examine the functional implications of MOR sensitivity within these afferent pathways.