Arousal Regulation Research Articles

Regulation of wakefulness by neurotensin neurons in the lateral hypothalamus

The lateral hypothalamic region (LH) has been identified as a key region for arousal regulation, yet the specific cell types and underlying mechanisms are not fully understood. While neurons expressing orexins (OX) are considered the primary wake-promoting population in the LH, their loss does not reduce daily wake levels, suggesting the presence of additional wake-promoting populations. In this regard, we recently discovered that a non-OX cell group in the LH, marked by the expression of neurotensin (Nts), could powerfully drive wakefulness. Activation of these NtsLH neurons elicits rapid arousal from non-rapid eye movement (NREM) sleep and produces uninterrupted wakefulness for several hours in mice. However, it remains unknown if these neurons are necessary for spontaneous wakefulness and what their precise role is in the initiation and maintenance of this state. To address these questions, we first examined the activity dynamics of the NtsLH population across sleep-wake behavior using fiber photometry. We find that NtsLH neurons are more active during wakefulness, and their activity increases concurrently with, but does not precede, wake-onset. We then selectively destroyed the NtsLH neurons using a diphtheria-toxin-based conditional ablation method, which significantly reduced wake amounts and mean duration of wake bouts and increased the EEG delta power during wakefulness. These findings demonstrate a crucial role for NtsLH neurons in maintaining normal arousal levels, and their loss may be associated with chronic sleepiness in mice.

EEG measures of brain arousal in relation to symptom improvement in patients with major depressive disorder: Results from a randomized placebo-controlled clinical trial

Hyperstable arousal regulation during a 15-min resting electroencephalogram (EEG) has been linked to a favorable response to antidepressants. The EMBARC study, a multicenter randomized placebo-controlled clinical trial, provides an opportunity to examine arousal stability as putative antidepressant response predictor in short EEG recordings. We tested the hypothesis that high arousal stability during a 2-min resting EEG at baseline is related to better outcome in the sertraline arm and explored the specificity of this effect. Outpatients with chronic/recurrent MDD were recruited from four university hospitals and randomized to treatment with sertraline (n = 100) or placebo (n = 104). The change in the Hamilton Rating Scale for Depression (HRSD-17) was the main outcome. Patients were stratified into high and low arousal stability groups. In mixed-model repeated measures (MMRM) analysis HRSD-17 change differed significantly between arousal groups, with high arousal stability being associated with a better outcome in the sertraline arm, and worse outcome in the placebo arm at week 4, with moderate effect sizes. When considering both treatment arms, a significant arousal group x time x treatment interaction emerged, highlighting specificity to the sertraline arm. Although findings indicate that arousal stability is likely to be a treatment-specific marker of response, further out-of-sample validation is warranted.

Sex-Specific Roles of Hypocretin Receptor Signaling in CRF Neurons on Alcohol Drinking, Anxiety, and BNST Neuronal Excitability.

Alcohol use disorder (AUD) is characterized by compulsive alcohol consumption and negative emotional states during withdrawal, often perpetuating a cycle of addiction through arousal dysfunction. The hypocretin/orexin (Hcrt) neuropeptide system, a key regulator of arousal, has been implicated in these processes, particularly in its interactions with corticotropin-releasing factor (CRF) neurons within the bed nucleus of the stria terminalis (BNST). We investigated the role of Hcrt receptor signaling in CRF neurons in modulating alcohol intake, anxiety behaviors, and BNST excitability, with a focus on sex-specific differences. Using CRF-specific genetic deletion of HcrtR1 and/or HcrtR2 receptors in mice, we found that deletion of HcrtR1 significantly reduced alcohol intake, with sex-specific effects on BNST excitability. CRF-specific HcrtR2 deletion, while not affecting alcohol consumption, decreased baseline anxiety-like behaviors in males relative to females. Moreover, the double deletion of both Hcrt receptors from CRF neurons led to reduced alcohol drinking in males and dampened anxiety behaviors and BNST excitability in both sexes during protracted withdrawal. These findings suggest that Hcrt signaling in CRF neurons plays a critical role in the persistence of excessive alcohol consumption and the development of negative affective states, with distinct contributions from HcrtR1 and HcrtR2. The observed sex-specific differences underscore the need for tailored therapeutic approaches targeting the Hcrt system in the treatment of AUD.

Mental processes in professional football players.

Clear connections have been found between mental processes and performance in elite level football. Yet, few studies have investigated how professional football players' experience the influence of mental processes on performance. This study used a qualitative research design and in-depth interview of six Norwegian professional football players at elite level with a mean age of 28, 3 years and represented five professional clubs. The aim of the study was to investigate how they perceived the importance of arousal regulation, mental toughness, and self-confidence, and that of the sport psychologist in developing these skills. The results revealed a complex and multifaceted link between mental processes and performance. All players, demonstrate a conscious awareness of how mental processes influence their performance. The use of a sport psychologist in working with mental processes emerges as a crucial factor for developing their mental skills. Another important aspect is the need for increased knowledge about mental training's effect in elite football. Mental toughness emerges as the most significant mental process for players' performance because it makes them capable of coping with challenging situations and periods. This study shows that mental processes are important for performing, both related to arousal regulation, and self-confidence, and especially mental toughness. However, mental toughness was also considered a product of age and experience, where older players tend to have experience of more situations that enable them to handle adversity better than younger players. Interestingly, the youngest players seem to be most aware of the use of a sports psychologist.

A hypothalamus-lateral periaqueductal gray GABAergic neural projection facilitates arousal following sevoflurane anesthesia in mice.

The lateral hypothalamus (LHA) is an evolutionarily conserved structure that regulates basic functions of an organism, particularly wakefulness. To clarify the function of LHAGABA neurons and their projections on regulating general anesthesia is crucial for understanding the excitatory and inhibitory effects of anesthetics on the brain. The aim of the present study is to investigate whether LHAGABA neurons play either an inhibitory or a facilitatory role in sevoflurane-induced anesthetic arousal regulation. We used fiber photometry and immunofluorescence staining to monitor changes in neuronal activity during sevoflurane anesthesia. Opto-/chemogenetic modulations were employed to study the effect of neurocircuit modulations during the anesthesia. Anterograde tracing was used to identify a GABAergic projection from the LHA to a periaqueductal gray (PAG) subregion. c-Fos staining showed that LHAGABA activity was inhibited by induction of sevoflurane anesthesia. Anterograde tracing revealed that LHAGABA neurons project to multiple arousal-associated brain areas, with the lateral periaqueductal gray (LPAG) being one of the dense projection areas. Optogenetic experiments showed that activation of LHAGABA neurons and their downstream target LPAG reduced the burst suppression ratio (BSR) during continuous sevoflurane anesthesia. Chemogenetic experiments showed that activation of LHAGABA and its projection to LPAG neurons prolonged the anesthetic induction time and promoted wakefulness. In summary, we show that an inhibitory projection from LHAGABA to LPAGGABA neurons promotes arousal from sevoflurane-induced loss of consciousness, suggesting a complex control of wakefulness through intimate interactions between long-range connections.

Contemporary neuroscientific concepts and psychotherapy: possibilities for integration

The article presents a review and analysis of literature aimed at grounding psychotherapy within the context of contemporary neuroscientific concepts. It is suggested that on the neural level psychotherapy is associated with changes in the mentalizing and empathy networks’ connectivity. Several mechanisms underlying these changes are proposed: enhancement of the prefrontal system’s role in arousal regulation, oxytocin-related modulation of the attachment system, and optimization of predictive coding of interpersonal perception, including the prediction error processing pathway. The hypotheses are supported by studies in social, cognitive, affective and behavioral neuroscience, research in the field of psychotherapy, and neuroimaging data on the effects of psychotherapy.

Insomnia symptom severity and dynamics of arousal-related symptoms across the day.

Arousal is a central component of many emotional symptoms and can contribute to insomnia. Here we assessed how the timing and fluctuating nature of arousal-related symptoms over the course of the day relate to insomnia symptom severity. In this study, 361 participants (M age = 31.9 years, 282 women, 77 men, 2 non-binary individuals) completed the Insomnia Severity Index to assess severity of insomnia symptoms, followed by repeated ratings of anxiety or nervousness, stress, sleepiness, and feeling down via their mobile phone between ~08:00 hours and 00:00 hours across 1 day. Measures of dynamics included: mean levels across the day; variation (standard deviation); instability (mean squared successive differences); and resistance to change/inertia (first-order autocorrelation). Time-of-day patterns were modelled using generalized additive mixed effects models. Insomnia symptom severity (mean Insomnia Severity Index = 9.1, SD = 5.2, range 0-25) was associated with higher mean levels of all arousal-related symptoms, and increased instability and variation throughout the day in anxiety or nervousness, stress, and feeling down. Resistance to change (inertia) was not associated with insomnia symptom severity. Generalized additive mixed effects analyses showed that while individuals with more severe insomnia symptoms had elevated symptoms across the entire day, they were especially more anxious or nervous and sleepy in the early morning (~08:00 hours), anxious or nervous, stressed and sleepy in the late afternoon/early evening (~16:00 hours-21:00 hours), and anxious or nervous and stressed in the late evening (~22:00 hours). Remarkably, higher arousal occurred in the presence of high subjective sleepiness. Together these results indicate that insomnia symptom severity is associated with problems with daytime and evening arousal regulation.

Sex differences in the prospective association of excessively long reaction times and hazardous cannabis use at six months

ObjectiveThe neurocognitive risk mechanisms predicting divergent outcomes likely differ between men and women who use cannabis recreationally. Increasingly, the use of descriptive distributions including the ex-Gaussian has been applied to draw stronger inferences about neurocognitive health in clinical populations. The current project examines whether the long tail of reaction times (RTs) in a distribution, as characterized by the ex-Gaussian parameter tau which may represent difficulty with the regulation of arousal, predicts problematic cannabis use 6 months later in those who use cannabis recreationally, and whether sex moderates these prospective associations. MethodYoung adults (ages 18–30, mean age 20.5 years, N =159, 57.2% women, 69.2% Caucasian) who recreationally used cannabis either occasionally (at least once per month) or frequently (three times or more per week) completed the Stroop Color-Word Task at baseline. Ex-Gaussian parameter tau was estimated for each participant. Self-report of hazardous cannabis use (CUDIT-R) and dysregulation of negative (DERS) and positive emotions (DERS-Positive) were obtained at baseline and 6-month follow-up. ResultsFor those with larger tau at baseline, being a man (but not a woman) was associated with increased difficulty regulating positive emotions concurrently (b = −0.01, F (1,159) = 5.48, p = 0.02), and with hazardous cannabis use six months later (b = −0.007, F (1,159) = 4.42, p = 0.037) after controlling for baseline hazardous cannabis use. ConclusionsExcessively long RTs during cognitive performance may help characterize men at risk for increased hazardous use, which contributes to understanding between-sex heterogeneity in pathways towards cannabis use disorders.

The Influence of Music on Athletic Performance

Purpose: This study sought to explore the influence of music on athletic performance. Methodology: The study adopted a desktop research methodology. Desk research refers to secondary data or that which can be collected without fieldwork. Desk research is basically involved in collecting data from existing resources hence it is often considered a low cost technique as compared to field research, as the main cost is involved in executive’s time, telephone charges and directories. Thus, the study relied on already published studies, reports and statistics. This secondary data was easily accessed through the online journals and library. Findings: The findings reveal that there exists a contextual and methodological gap relating to the influence of music on athletic performance. Preliminary empirical review revealed that music served as a potent tool for regulating arousal levels, enhancing motivation, and directing attentional focus during physical activity. By aligning music characteristics with athletes' preferences and task demands, coaches optimized performance outcomes. Moreover, personalized music selection facilitated motor coordination and cognitive engagement, contributing to improved performance and enjoyment of sports. Overall, the study emphasized the importance of considering individual differences and contextual factors in designing effective music interventions for athletes. Unique Contribution to Theory, Practice and Policy: The Arousal Regulation Theory, Synchronization Hypothesis and Attentional Focus Theory may be used to anchor future studies on the influence of music on athletic performance. The study offered comprehensive recommendations for theory, practice, and policy in sports and exercise contexts. These recommendations included integrating music interventions into training and competition protocols, tailoring music selection to individual preferences, and leveraging music's potential to enhance cognitive function and decision-making skills among athletes. Additionally, the study highlighted the importance of strategic manipulation of music tempo and characteristics to elicit specific psychological and physiological responses conducive to optimal performance. Further research was deemed necessary to explore the underlying mechanisms through which music influences athletic performance and to develop evidence-based guidelines for integrating music into sports practice and policy.

Research Progress in the Role of the Ventral Tegmental Area-Medial Prefrontal Cortex Neural Circuit in the Regulation of Arousal

There are mutual neural projections between the ventral tegmental area (VTA) and the medial prefrontal cortex (mPFC),which form a circuit.Recent studies have shown that this circuit is vital in regulating arousal from sleep and general anesthesia.This paper introduces the anatomical structures of VTA and mPFC and the roles of various neurons and projection pathways in the regulation of arousal,aiming to provide new ideas for further research on the mechanism of arousal from sleep and general anesthesia.

A cortical locus for modulation of arousal states.

Fluctuations in global arousal are key determinants of spontaneous cortical activity and function. Several subcortical structures, including neuromodulator nuclei like the locus coeruleus (LC), are involved in the regulation of arousal. However, much less is known about the role of cortical circuits that provide top-down inputs to arousal-related subcortical structures. Here, we investigated the role of a major subdivision of the prefrontal cortex, the anterior cingulate cortex (ACC), in arousal modulation. Pupil size, facial movements, heart rate, and locomotion were used as non-invasive measures of arousal and behavioral state. We designed a closed loop optogenetic system based on machine vision and found that real time inhibition of ACC activity during pupil dilations suppresses ongoing arousal events. In contrast, inhibiting activity in a control cortical region had no effect on arousal. Fiber photometry recordings showed that ACC activity scales with the magnitude of spontaneously occurring pupil dilations/face movements independently of locomotion. Moreover, optogenetic ACC activation increases arousal independently of locomotion. In addition to modulating global arousal, ACC responses to salient sensory stimuli scaled with the size of evoked pupil dilations. Consistent with a role in sustaining saliency-linked arousal events, pupil responses to sensory stimuli were suppressed with ACC inactivation. Finally, our results comparing arousal-related ACC and norepinephrinergic LC neuron activity support a role for the LC in initiation of arousal events which are modulated in real time by the ACC. Collectively, our experiments identify the ACC as a key cortical site for sustaining momentary increases in arousal and provide the foundation for understanding cortical-subcortical dynamics underlying the modulation of arousal states.

Interplay between sexual excitation and inhibition: impact on sexual function and neural correlates of erotic stimulus processing in women.

As outlined by the dual control model (DCM), individual differences in the regulation of sexual arousal following sexual stimulation depend on two distinct neurophysiological processes: sexual excitation (SE) and sexual inhibition (SI). Although associations with sexual function, behavior, and cue processing have been demonstrated in previous research, underlying neural correlates remain insufficiently explored. Moreover, interactive effects of SE/SI as proposed by the DCM, as well as factors impacting SE/SI properties, such as the use of oral contraceptives (OCs), have not received adequate attention in existing research. 90 healthy, sexually active women (n = 51 using OCs, n = 39 naturally cycling) completed an Emotional-Picture-Stroop-Paradigm (EPSP) while a 64-channel EEG was recorded. LPP amplitudes toward erotic and neutral stimuli were consecutively computed as a marker of motivational salience and approach motivation. Additionally, women provided self-reports of SE/SI and sexual function. Moderation analyses were performed to assess interactive effects of SE/SI in predicting LPP amplitudes and sexual function. Sexual function was negatively associated with SI levels but unrelated to SE. Higher SI was associated with reduced LPP amplitudes in response to erotic stimuli. This negative association was, however, attenuated for women high in SE, suggesting interactive effects of SE/SI. Furthermore, women using OCs reported lower SE compared to naturally cycling women. The observed findings provide additional psychophysiological evidence supporting the DCM and underscore the relevance of interactive SE/SI effects in stimulus processing and approach motivation. They also highlight the possible impact of OCs on psychosexual variables that warrants further research.

Neuroanatomical Substrates of Circuit-Specific Cholinergic Modulation across the Primate Anterior Cingulate Cortex.

Acetylcholine is a robust neuromodulator of the limbic system and a critical regulator of arousal and emotions. The anterior cingulate cortex (ACC) and the amygdala (AMY) are key limbic structures that are both densely innervated by cholinergic afferents and interact with each other for emotional regulation. The ACC is composed of functionally distinct dorsal (A24), rostral (A32), and ventral (A25) areas that differ in their connections with the AMY. The structural substrates of cholinergic modulation of distinct ACC microcircuits and outputs to AMY are thought to depend on the laminar and subcellular localization of cholinergic receptors. The present study examines the distribution of muscarinic acetylcholine receptors, m1 and m2, on distinct excitatory and inhibitory neurons and on AMY-targeting projection neurons within ACC areas, via immunohistochemistry and injections of neural tracers into the basolateral AMY in adult rhesus monkeys of both sexes. We found that laminar densities of m1+ and m2+ expressing excitatory and inhibitory neurons depended on area and cell type. Among the ACC areas, ventral subgenual ACC A25 exhibited greater m2+ localization on presynaptic inhibitory axon terminals and greater density of m1+ and m2+ expressing AMY-targeting (tracer+) pyramidal neurons. These patterns suggest robust cholinergic disinhibition and potentiation of amygdalar outputs from the limbic ventral ACC, which may be linked to the hyperexcitability of this subgenual ACC area in depression. These findings reveal the anatomical substrate of diverse cholinergic modulation of specific ACC microcircuits and amygdalar outputs that mediate cognitive-emotional integration and dysfunctions underlying stress and affective disorders.

Centripetal integration of past events in hippocampal astrocytes regulated by locus coeruleus.

An essential feature of neurons is their ability to centrally integrate information from their dendrites. The activity of astrocytes, in contrast, has been described as mostly uncoordinated across cellular compartments without clear central integration. Here we report conditional integration of calcium signals in astrocytic distal processes at their soma. In the hippocampus of adult mice of both sexes, we found that global astrocytic activity, as recorded with population calcium imaging, reflected past neuronal and behavioral events on a timescale of seconds. Salient past events, indicated by pupil dilations, facilitated the propagation of calcium signals from distal processes to the soma. Centripetal propagation to the soma was reproduced by optogenetic activation of the locus coeruleus, a key regulator of arousal, and reduced by pharmacological inhibition of α1-adrenergic receptors. Together, our results suggest that astrocytes are computational units of the brain that slowly and conditionally integrate calcium signals upon behaviorally relevant events.

Psychological Effects of Music in Exercise and Sports Performance

Purpose: The general purpose of this study was to examine the psychological effects of music in exercise and sports performance.
 Methodology: The study adopted a desktop research methodology. Desk research refers to secondary data or that which can be collected without fieldwork. Desk research is basically involved in collecting data from existing resources hence it is often considered a low cost technique as compared to field research, as the main cost is involved in executive’s time, telephone charges and directories. Thus, the study relied on already published studies, reports and statistics. This secondary data was easily accessed through the online journals and library.
 Findings: The findings reveal that there exists a contextual and methodological gap relating to technology and traditional arts in modern sporting events. Preliminary empirical review revealed that music significantly influences psychological states during physical activity. It found that music with faster tempos and motivational lyrics enhanced arousal, mood, and performance outcomes such as endurance and coordination. Additionally, personalized music interventions tailored to individual preferences maximized the performance-enhancing effects of music. The study emphasized the importance of considering both psychological and physiological responses to music in designing effective interventions for optimizing performance outcomes and promoting exercise adherence. Overall, the findings highlighted the intricate relationship between music and exercise performance and suggested potential avenues for future research in this area.
 Unique Contribution to Theory, Practice and Policy: Theory of Arousal Regulation, Self-Determination Theory (SDT) and Attentional Focus may be used to anchor future studies on psychological effects of music in exercise and sports performance. The study provided comprehensive recommendations that contributed to theory, practice, and policy in the field. Through theoretical development, the study refined existing frameworks such as the Theory of Arousal Regulation and Self-Determination Theory, deepening our understanding of how music influences psychological states in athletic contexts. Practical guidelines were established to integrate music into athlete preparation routines, emphasizing personalized playlists and warm-up protocols to optimize performance outcomes. Policy implications highlighted the need to institutionalize music-based interventions in sports programs, promoting athlete well-being and enjoyment. Furthermore, the study identified future research priorities, evaluation frameworks, and public health initiatives to advance the integration of music into exercise and sports settings, fostering physical activity participation and overall health.

A vertebrate family without a functional Hypocretin/Orexin arousal system

The Hypocretin/Orexin signaling pathway suppresses sleep and promotes arousal, whereas the loss of Hypocretin/Orexin results in narcolepsy, including the involuntary loss of muscle tone (cataplexy).1 Here, we show that the South Asian fish species Chromobotia macracanthus exhibits a sleep-like state during which individuals stop swimming and rest on their side. Strikingly, we discovered that the Hypocretin/Orexin system is pseudogenized in C.macracanthus, but in contrast to Hypocretin-deficient mammals, C.macracanthus does not suffer from sudden behavioral arrests. Similarly, zebrafish mutations in hypocretin/orexin show no evident signs of cataplectic-like episodes. Notably, four additional species in the Botiidae family also lack a functional Hypocretin/Orexin system. These findings identify the first vertebrate family that does not rely on a functional Hypocretin/Orexin system for the regulation of sleep and arousal.

Altered EEG Patterns in Individuals with Disorganized Attachment: An EEG Microstates Study.

Over the past years, different studies provided preliminary evidence that Disorganized Attachment (DA) may have dysregulatory and disintegrative effects on both autonomic arousal regulation and brain connectivity. However, despite the clinical relevance of this construct, few studies have investigated the specific alterations underlying DA using electroencephalography (EEG). Thus, the main aim of the current study was to investigate EEG microstate parameters of DA in a non-clinical sample (N = 50) before (pre) and after (post) the administration of the Adult Attachment Interview (AAI). Two EEG eyes-closed Resting State (RS) recordings were performed before and after the AAI, which was used for classifying the participants [i.e., Disorganized/Unresolved (D/U) or Organized/Resolved (O/R) individuals] and to trigger the attachment system. Microstates parameters (i.e., Mean Duration, Time Coverage and Occurrence) were extracted from each recording using Cartool software. EEG microstates clustering analysis revealed 6 different maps (labeled A, B, C, D, E, F) in both groups (i.e., D/U and O/R individuals) and in both conditions (i.e., pre-AAI and post-AAI). In the pre-AAI condition, compared to O/R individuals, D/U participants showed a shorter Mean Duration and Time Coverage of Map F; in the post-AAI condition, a significant reduction in the Mean Duration of Map E was also observed in D/U individuals. Finally, in the "within" statistical analysis (i.e., pre-AAI vs. post-AAI), only the D/U group exhibited a significant increase in Time Coverage of Map F after the AAI. Since these maps are associated with brain networks involved in emotional information processing and mentalization (i.e., Salience Network and Default Mode Network), our result might reflect the deficit in the ability to mentalize caregiver's interaction as well as the increased sensitivity to attachment-related stimuli typically observed in individuals with a D/U state of mind.

Positive Emotion Is Associated with Attentional Focus on Physical Activity and Eating in Adolescents: A Daily Diary Study.

There are emerging data linking positive emotion to health behaviors, yet the self-regulatory processes underlying this link are understudied. The purpose of the current study was to examine the associations between daily positive emotion and daily attentional focus on physical activity and overeating as well as the moderating role of trait positive emotion arousal recovery. Adolescents (N = 47) aged 11 to 17 completed a baseline measure of their perceived positive emotion arousal regulation and a 7-day diary about their positive emotion and attentional focus. Both within-person increases in and greater average daily approach-oriented positive emotion were associated with greater daily attentional focus on physical activity and overeating. Quicker perceived trait approach-oriented positive emotion arousal recovery dampened the association between within-person increases in daily approach-motivated positive emotion and daily attentional focus on overeating but not physical activity. Positive emotion can elicit a narrowing of attentional focus towards emotionally salient health behavior. Future studies should examine the full mechanistic pathway linking positive emotion to health behavior via attentional focus and arousal recovery.

The impact of emotional dysregulation and comorbid depressive symptoms on clinical features, brain arousal, and treatment response in adults with ADHD.

The role of emotional dysregulation (ED) in attention-deficit/hyperactivity disorder (ADHD) has become an important issue. This study, in which we analyzed data from a predictive pharmaco-EEG-trial, aimed to examine whether symptoms of ED in adult ADHD affect ADHD symptom severity, brain arousal regulation as measured by resting EEG, and the response to stimulant medication. ED is defined as having a sex- and age-corrected T-score of >70 on the emotional lability subscale of the German version of Conners' Adult ADHD Rating Scale. A total of 115 participants were included in the study, 56 of whom had ED. Participants with ED were more impaired in terms of the severity of core ADHD symptoms, especially inattentive symptoms, comorbid depressive symptoms, interpersonal relationships, and quality of life. In addition, participants with ED were more likely to report a total score above 13 on the Beck Depression Inventory-II, which was considered to be the cutoff for mild depression. No differences were found between the ED and non-ED groups in response to stimulant medication or in brain arousal regulation. In addition, there was no significant effect of ED with comorbid depressive symptoms on treatment response. There was a trend for subgroups that showed a change in brain arousal regulation associated with symptom improvement. Our findings may support the assumption that ED may be an important feature of ADHD. The use of EEG-based brain arousal regulation as a diagnostic and predictive tool in ADHD in the presence of ED and comorbid depressive symptoms should be further investigated.

Cerebellar Purkinje cell firing promotes conscious recovery from anesthesia state through coordinating neuronal communications with motor cortex.

Background: The neurobiological basis of gaining consciousness from unconscious state induced by anesthetics remains unknown. This study was designed to investigate the involvement of the cerebello-thalamus-motor cortical loop mediating consciousness transitions from the loss of consciousness (LOC) induced by an inhalational anesthetic sevoflurane in mice. Methods: The neural tracing and fMRI together with opto-chemogenetic manipulation were used to investigate the potential link among cerebello-thalamus-motor cortical brain regions. The fiber photometry of calcium and neurotransmitters, including glutamate (Glu), γ-aminobutyric acid (GABA) and norepinephrine (NE), were monitored from the motor cortex (M1) and the 5th lobule of the cerebellar vermis (5Cb) during unconsciousness induced by sevoflurane and gaining consciousness after sevoflurane exposure. Cerebellar Purkinje cells were optogenetically manipulated to investigate their influence on consciousness transitions during and after sevoflurane exposure. Results: Activation of 5Cb Purkinje cells increased the Ca2+ flux in the M1 CaMKIIα+ neurons, but this increment was significantly reduced by inactivation of posterior and parafascicular thalamic nucleus. The 5Cb and M1 exhibited concerted calcium flux, and glutamate and GABA release during transitions from wakefulness, loss of consciousness, burst suppression to conscious recovery. Ca2+ flux and Glu release in the M1, but not in the 5Cb, showed a strong synchronization with the EEG burst suppression, particularly, in the gamma-band range. In contrast, the Glu, GABA and NE release and Ca2+ oscillations were coherent with the EEG gamma band activity only in the 5Cb during the pre-recovery of consciousness period. The optogenetic activation of Purkinje cells during burst suppression significantly facilitated emergence from anesthesia while the optogenetic inhibition prolonged the time to gaining consciousness. Conclusions: Our data indicate that cerebellar neuronal communication integrated with motor cortex through thalamus promotes consciousness recovery from anesthesia which may likely serve as arousal regulation.