Hippocampal barques and their manifestation as 14&6 Hz positive spikes during sleep.

OBJECTIVE: This study investigates variations in hippocampal barque occurrence during sleep and compares findings to respective variations of their scalp manifestation as 14&6/sec positive spikes. METHODS: From 11 epilepsy patients, 12 non-epileptogenic hippocampi with barques were identified for this study. Using the first seizure-free whole-night sleep stereo-encephalography (sEEG) recording, we performed sleep staging and measured the occurrence of barques and 14&6/sec positive spikes variants. RESULTS: Hippocampal barques (total count: 9,183; mean count per record: 765.2 ± 251.2) occurred predominantly during non-rapid eye movement (NREM) II sleep (total: 5,744; mean: 478.6 ± 176.1; 62.2 ± 6.0%) and slow-wave sleep (SWS) (total: 2,950; mean: 245.83 ± 92.9; 32.0 ± 6.2%), with rare to occasional occurrence in NREM I (total: 85; mean: 7.0 ± 2.8; 0.9 ± 0.4%), rapid eye movement (REM) (total: 153; mean: 12.75 ± 4.0; 1.7 ± 0.6) and wakefulness (total: 251; mean: 20.9 ± 6.3; 2.9 ± 0.9%). Barque rate increased during SWS (mean: 2.7 ± 1.0 per min) compared to NREM II (2.2 ± 1.0 per min) and other states (wakefulness: 0.1 ± 0.0 per min; NREM I: 0.3 ± 0.1 per min; REM: 0.1 ± 0.0 per min). The 14&6/sec positive spikes variant (total count: 2,406; mean: 343.7 ± 106.7) was present in NREM II (total: 2,059; mean: 249.1 ± 100.2, 84.9 ± 3.6%) and SWS (total: 347; mean: 49.5 ± 12.8, 15.0 ± 3.6%) stages, and absent from the rest of sleep and wakefulness. While all 14&6/sec positive spikes correlated with barques, only 44.7 ± 6.1% of barques manifested as 14&6/sec positive spikes. CONCLUSIONS: Hippocampal barques are predominant in NREM II and SWS, and tend to increase their presence during SWS. Their scalp manifestation as 14&6/sec positive spikes is confounded by wakefulness, REM and NREM I stages, and "masked" by the co-occurrence of NREM II and SWS slow waves, and overlapping reactive micro-arousal elements. SIGNIFICANCE: Our study highlighted the overnight profile of hippocampal barques, in relation to the respective profile of their scalp manifestation, the 14&6/sec positive spikes variant.

Clinical characterisation of women with persistent genital arousal disorder: the iPGAD-study.

Persistent Genital Arousal Disorder (PGAD) is a rare condition-mostly in women-where patients perceive prolonged genital arousal without any sexual desire or stimulation. Etiopathological considerations reach from peripheral to central issues over local disturbance of the pudendal nerve to neuropathy, psychosocial, and pharmacological theories. Since well controlled clinical studies about PGAD in conjunction with a mental and somatic health status are missing, this study is a detailed clinical investigation of PGAD patients compared to healthy controls. 26 women who fulfilled diagnostic criteria for PGAD were compared to 26 age matched healthy controls. Investigations included comparison of vegetative, gynaecological and sexual history, psychiatric features as well as a (neuro-)radiological, neurophysiological and gynaecological examination. Moreover, a detailed clinical characterisation of PGAD symptoms was performed. PGAD symptoms were mostly characterised as tingling or prickling and were permanently present. In over 80%, PGAD symptoms were located in the clitoris. Almost 70% reported radiations to other regions of the body. Most frequent trigger factors were tight clothes, mental stress, driving a car/bus/bicycle and sexual intercourse. Relieving factors were mainly distraction, relaxation, physical exercise, masturbation and swimming. In group comparisons, PGAD presented with significant higher rates of sexual dysfunctions, spontaneous orgasms, swelling of the genitals, extraordinary lubrication as well as higher rates in depression, agoraphobia, generalized anxiety disorder and lifetime panic disorder. Significantly more PGAD patients were diagnosed with restless legs symptoms. In contrast childhood traumatization, somatization disorder, suicidality, gynaecological as well as neurophysiological examination of the pudendal nerve were not different between the groups. MRI of the brain, pelvis and spinal cord was unsuspicious and incidental findings - including Tarlov cysts or pelvic venous congestion - were equally distributed among the groups. In summary, our study provides a careful characterization of women with PGAD highlighting a serious mental burden, most probably as a consequence of PGAD. With the current set of clinical investigations there was no evidence of a clear causal relationship to a specific clinical finding as it has been previously discussed. Future studies and additional techniques will have to further explore where and how in the peripheral or central nervous systems PGAD develops.

Bidirectional relationship between sexual arousal and (sex-related) disgust.

Sexual stimuli provoke both sexual arousal and disgust, and the coaction between these emotions determines sexually behavioral outcomes. The current research includes two experiments to explore the bidirectional relationship between sexual arousal toward erotic stimuli and disgust induced by sexual body fluids. Study 1 presented 234 participants (117 women) with sexual body (vs. neutral) fluids followed by erotic stimuli, and Study 2 presented 235 participants (117 women) with erotic (vs. neutral) videos followed by sexual body fluids (and a non-sex-related stimulus). Study 1 showed that exposure to sexual body fluids reduced sexual arousal and the likelihood of sexual engagement toward erotic stimuli in participants with high sexual disgust sensitivity but increased sexual arousal and the likelihood of sexual engagement in participants with low sexual disgust sensitivity, while Study 2 suggested that men exposed to erotic (vs. neutral) stimuli reported lower disgust, stronger sexual arousal state, and higher willingness to interact with the sexual body fluids. There was no relationship between subjective feelings of sexual arousal and disgust in these experiments, while the balance of sexual arousal and disgust toward sexual body fluids and erotic stimuli had a positive association. Also, exposure to erotic stimuli had no effect on reactions to generally disgusting stimulus, but feelings of sexual arousal toward erotic stimuli were positively associated with disgust induced by generally disgusting fluid. These findings suggest that Behavior Immune System regulates disgust to establish a balance between benefit and cost related to sex as well as provide insight into the process underlying sexual dysfunctions.

Assessing Affective Valence and Activation in Stretching Activities with the Feeling Scale and the Felt Arousal Scale: A Systematic Review.

Affective responses have been considered key determinants for exercise adherence, but research on affective responses to stretching activities is scarce. Given the role of these responses in exercise adherence, our aim in this review was to explore (a) the utility and feasibility of core affect in stretching-related activities as measured by the Feeling Scale (FS) and/or the Felt Arousal Scale (FAS); (b) the timing of administering these scales; and (c) the scales' applicability and interpretability in this context. Inclusion criteria for studies in this review were experimental and non-experimental studies written in English that based affect assessment on the FS and/or FAS and that applied these scales to participants engaged in physical activity, individually or in groups. We also considered studies that focused on stretching activities that were either isolated or components of a class/activity and studies that used healthy participants of any age. Exclusion criteria were populations with mental health problems, cancer, diabetes, hypertension, cardiovascular disease, or diseases likely to alter pain perception or be associated with chronic pain, instrument validation studies, gray literature, and systematic reviews. We searched PubMed, SPORTDiscus and PsycINFO databases, and we added studies retrieved manually from reference sections while following PRISMA guidelines. We used the Effective Public Health Practice Project tool for judging methodological quality of research articles. Our final analyses were based on 12 empirical studies published between 2003 and 2021with a total of 718 participants. Both scales were found to be useful and feasible in the most usual places for exercise, but core affect results cannot be properly interpreted due to variability of study protocols and the absence of guidelines for adequate baseline assessment. Most studies recorded affect responses pre-session, during session, and post-session. We observed no standardized timing or frequency of assessment, and there was high heterogeneity among stretching protocols. Currently, research in core affect assessment of stretching-related activities lacks sufficient methodological quality to draw generalizable conclusions.

A gut-secreted peptide suppresses arousability from sleep.

Suppressing sensory arousal is critical for sleep, with deeper sleep requiring stronger sensory suppression. The mechanisms that enable sleeping animals to largely ignore their surroundings are not well understood. We show that the responsiveness of sleeping flies and mice to mechanical vibrations is better suppressed when the diet is protein rich. In flies, we describe a signaling pathway through which information about ingested proteins is conveyed from the gut to the brain to help suppress arousability. Higher protein concentration in the gut leads to increased activity of enteroendocrine cells that release the peptide CCHa1. CCHa1 signals to a small group of dopamine neurons in the brain to modulate their activity; the dopaminergic activity regulates the behavioral responsiveness of animals to vibrations. The CCHa1 pathway and dietary proteins do not influence responsiveness to all sensory inputs, showing that during sleep, different information streams can be gated through independent mechanisms.

Same but different: The influence of context framing on subjective disgust, eye movements and pupillary responses.

The adaptive value of disgust has been associated with situations of threat to our survival. This study explored this topic using eye-tracking, which provides an objective measurement of attention, while solving previous methodological issues (e.g., not considering discrete emotions and comparing across perceptually-different stimuli). We used the same stimuli and manipulated the emotional state via contextual framing. Participants' eye movements and pupillary responses were recorded while they explored pictures of objects held by clean or dirty hands; the latter were framed in a disease or a non-disease context. Pictures were then rated for arousal, disgust, and valence. Framing stimuli in a disease (vs non-disease) context induced a more adverse subjective emotional experience. Importantly, our objective measures revealed that such manipulation also led to a higher information-seeking behavior and greater pupil constriction. Overall, our data suggest that the same stimuli can effectively be used to induce different emotional states by manipulating their framing.

Electrophysiological normative responses to emotional, neutral, and cigarette-related images.

To create reproducible emotional probes, affective scientists rely on sets of standardized pictures that are normed using subjective ratings of valence and emotional arousal. However, when emotional responses are investigated using neurophysiological measures, it might be more appropriate to select pictures integrating information from normative subjective reports and normative neurophysiological responses. Here, we provide electrophysiological normative responses for 323 emotional pictures (215 from the IAPS) covering a wide range of categories (erotica, romantic, appetizing foods, landscapes, people engaged in mundane activities, household objects, disgusting objects, accidents, sad people, violence, mutilations, and cigarette-related contents). Event-related potentials (ERPs) and subjective ratings of pleasure and emotional arousal were collected from 763 individuals (52% females, 41% white) aged between 18 and 65 (mean = 43). For each image, the mean amplitude of the late positive potential (LPP, an electrophysiological index of motivational relevance) and the mean subjective ratings of valence and arousal were calculated. We validated our procedure by showing that the subjective ratings of valence and arousal from this sample were highly correlated to the IAPS' published norms (Pearson r = .97 for pleasure and r = .82 for emotional arousal). LPP responses and subjective ratings of emotional arousal also were correlated (Pearson r = .61), but some categories reported being significantly more arousing than neutral (i.e., food, landscapes, and unpleasant objects) did not evoke LPPs significantly different from those evoked by neutral pictures. Researchers interested in probing the brain's affective systems can use these electrophysiological normative responses to create emotional probes that evoke reliable neuroaffective responses.

An Ensemble Learning Method for Emotion Charting Using Multimodal Physiological Signals.

Emotion charting using multimodal signals has gained great demand for stroke-affected patients, for psychiatrists while examining patients, and for neuromarketing applications. Multimodal signals for emotion charting include electrocardiogram (ECG) signals, electroencephalogram (EEG) signals, and galvanic skin response (GSR) signals. EEG, ECG, and GSR are also known as physiological signals, which can be used for identification of human emotions. Due to the unbiased nature of physiological signals, this field has become a great motivation in recent research as physiological signals are generated autonomously from human central nervous system. Researchers have developed multiple methods for the classification of these signals for emotion detection. However, due to the non-linear nature of these signals and the inclusion of noise, while recording, accurate classification of physiological signals is a challenge for emotion charting. Valence and arousal are two important states for emotion detection; therefore, this paper presents a novel ensemble learning method based on deep learning for the classification of four different emotional states including high valence and high arousal (HVHA), low valence and low arousal (LVLA), high valence and low arousal (HVLA) and low valence high arousal (LVHA). In the proposed method, multimodal signals (EEG, ECG, and GSR) are preprocessed using bandpass filtering and independent components analysis (ICA) for noise removal in EEG signals followed by discrete wavelet transform for time domain to frequency domain conversion. Discrete wavelet transform results in spectrograms of the physiological signal and then features are extracted using stacked autoencoders from those spectrograms. A feature vector is obtained from the bottleneck layer of the autoencoder and is fed to three classifiers SVM (support vector machine), RF (random forest), and LSTM (long short-term memory) followed by majority voting as ensemble classification. The proposed system is trained and tested on the AMIGOS dataset with k-fold cross-validation. The proposed system obtained the highest accuracy of 94.5% and shows improved results of the proposed method compared with other state-of-the-art methods.

Examining the impact of multilevel upper airway surgery on the obstructive sleep apnoea endotypes and their utility in predicting surgical outcomes.

BACKGROUND AND OBJECTIVE: Upper airway surgery for obstructive sleep apnoea (OSA) is an alternative treatment for patients who are intolerant of continuous positive airway pressure (CPAP). However, upper airway surgery has variable treatment efficacy with no reliable predictors of response. While we now know that there are several endotypes contributing to OSA (i.e., upper airway collapsibility, airway muscle response/compensation, respiratory arousal threshold and loop gain), no study to date has examined: (i) how upper airway surgery affects all four OSA endotypes, (ii) whether knowledge of baseline OSA endotypes predicts response to surgery and (iii) whether there are any differences when OSA endotypes are measured using the CPAP dial-down or clinical polysomnographic (PSG) methods. METHODS: We prospectively studied 23 OSA patients before and ≥3 months after multilevel upper airway surgery. Participants underwent clinical and research PSG to measure OSA severity (apnoea-hypopnoea index [AHI]) and endotypes (measured in supine non-rapid eye movement [NREM]). Values are presented as mean ± SD or median (interquartile range). RESULTS: Surgery reduced the AHITotal (38.7 [23.4 to 79.2] vs. 22.0 [13.3 to 53.5] events/h; p = 0.009). There were no significant changes in OSA endotypes, however, large but variable improvements in collapsibility were observed (CPAP dial-down method: ∆1.9 ± 4.9 L/min, p = 0.09, n = 21; PSG method: ∆3.4 [-2.8 to 49.0]%Veupnoea , p = 0.06, n = 20). Improvement in collapsibility strongly correlated with improvement in AHI (%∆AHISupineNREM vs. ∆collapsibility: p < 0.005; R2  = 0.46-0.48). None of the baseline OSA endotypes predicted response to surgery. CONCLUSION: Surgery unpredictably alters upper airway collapsibility but does not alter the non-anatomical endotypes. There are no baseline predictors of response to surgery.

Treatments for Persistent Genital Arousal Disorder in Women: A Scoping Review.

BACKGROUND: Persistent genital arousal disorder (PGAD) is characterized by elevated discomfort associated with persistent genital arousal in the absence of sexual desire. AIM: To perform a scoping review of the proposed treatments for PGAD and their efficacy. METHODS: A scoping review was carried out (PRISMA-Scr) that included articles on PGAD as the main disorder, only in women, which explained, in detail, the treatment and its efficacy, was empirical, was written in English and Spanish. No prior filtering by years was performed. OUTCOMES: Three different effective treatments were found (Physical therapies, pharmacological therapies, and psychotherapeutics in combination with other therapies). RESULTS: Thirty-eight articles were selected. From physical therapies, treatments using neuromodulation, transcutaneous electrical stimulation, Botox, surgery, electroconvulsive therapy, manual therapy, pelvic floor therapy, dietary changes, and transcranial magnetic stimulation showed effectiveness. Using the pharmacological approach, paroxetine, duloxetine, pramipexole, ropinirole, and clonazepam treatments were effective. Psychotherapy treatments showed effectiveness only in combination with other types of treatments, specifically a combination of cognitive-behavioral strategies with pharmacological treatment. CLINICAL IMPLICATIONS: Pharmacological treatment, specifically SSRIs, have proven to be the therapy of choice for different subtypes of patients. STRENGTHS AND LIMITATIONS: This study analyzed treatment effectiveness with different approaches and took into consideration those articles where psychotherapy was used as a combination treatment with pharmacological and physical therapy. The main limitation is that it was focused exclusively on women, and the results cannot be generalized to include men. CONCLUSIONS: To date, a combination of pharmacological interventions with physical therapy and, in some occasions, with psychological therapy is main strategy followed to accomplish effective treatment of PGAD. Martín-Vivar M, Villena-Moya A, Mestre-Bach G, et al. Treatments for Persistent Genital Arousal Disorder in Women: A Scoping Review. J Sex Med 2022;19:961-974.

Dysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in mice.

Hypersomnolence disorder (HD) is characterized by excessive sleep, which is a common sequela following stroke, infection, or tumorigenesis. HD is traditionally thought to be associated with lesions of wake-promoting nuclei. However, lesions of a single wake-promoting nucleus, or even two simultaneously, did not exert serious HD. Therefore, the specific nucleus and neural circuitry for HD remain unknown. Here, we observed that the paraventricular nucleus of the hypothalamus (PVH) exhibited higher c-fos expression during the active period (23:00) than during the inactive period (11:00) in mice. Therefore, we speculated that the PVH, in which most neurons are glutamatergic, may represent one of the key arousal-controlling centers. By using vesicular glutamate transporter 2 (vglut2Cre) mice together with fiber photometry, multichannel electrophysiological recordings, and genetic approaches, we found that PVHvglut2 neurons were most active during wakefulness. Chemogenetic activation of PVHvglut2 neurons induced wakefulness for 9 hr, and photostimulation of PVHvglut2→parabrachial complex/ventral lateral septum circuits immediately drove transitions from sleep to wakefulness. Moreover, lesioning or chemogenetic inhibition of PVHvglut2 neurons dramatically decreased wakefulness. These results indicate that the PVH is critical for arousal promotion and maintenance.

Failure to detect ward hypoxaemia and hypotension: contributions of insufficient assessment frequency and patient arousal during nursing assessments.

BACKGROUND: Postoperative hypotension and hypoxaemia are common and often unrecognised. With intermittent nursing vital signs, hypotensive or hypoxaemic episodes might be missed because they occur between scheduled measurements, or because the process of taking vital signs arouses patients and temporarily improves arterial blood pressure and ventilation. We therefore estimated the fraction of desaturation and hypotension episodes that did not overlap nursing assessments and would therefore usually be missed. We also evaluated the effect of taking vital signs on blood pressure and oxygen saturation. METHODS: We estimated the fraction of desaturated episodes (arterial oxygen saturation <90% for at least 90% of the time within 30 continuous minutes) and hypotensive episodes (MAP <70 mm Hg for 15 continuous minutes) that did not overlap nursing assessments in patients recovering from noncardiac surgery. We also evaluated changes over time before and after nursing visits. RESULTS: Among 782 patients, we identified 878 hypotensive episodes and 2893 desaturation episodes, of which 79% of the hypotensive episodes and 82% of the desaturation episodes did not occur within 10 min of a nursing assessment and would therefore usually be missed. Mean BP and oxygen saturation did not improve by clinically meaningful amounts during nursing vital sign assessments. CONCLUSIONS: Hypotensive and desaturation episodes are mostly missed because vital sign assessments on surgical wards are sparse, rather than being falsely negative because the assessment process itself increases blood pressure and oxygen saturation. Continuous vital sign monitoring will detect more disturbances, potentially giving clinicians time to intervene before critical events occur.

Rapid eye movement sleep and slow wave sleep rebounded and related factors during positive airway pressure therapy.

This study aimed to investigate the clinical characteristics and predictors of increased rapid eye movement (REM) sleep or slow wave sleep (SWS) in patients with obstructive sleep apnea (OSA) following positive airway pressure (PAP) therapy. The study retrospectively analyzed data from patients with OSA who underwent both diagnostic polysomnography (PSG) and pressure titration PSG at the Tangdu Hospital Sleep Medicine Center from 2011-2016. Paired diagnostic PSG and pressure titration studies from 501 patients were included. REM rebound was predicted by a higher oxygen desaturation index, lower REM proportion, higher arousal index, lower mean pulse oxygen saturation (SpO2), higher Epworth sleepiness score and younger age (adjusted R2 = 0.482). The SWS rebound was predicted by a longer total duration of apneas and hypopneas, lower N3 duration, lower SpO2 nadir, lower REM proportion in diagnostic PSG and younger age (adjusted R2 = 0.286). Patients without REM rebound or SWS rebound had a high probability of comorbidities with insomnia and mood complaints. Some parameters (subjective and objective insomnia, excessive daytime sleepiness, age and OSA severity) indicate changes in REM sleep and SWS between diagnostic and titration PSG tests. Treatment of insomnia and mood disorders in patients with OSA may helpful to improve the use PAP.

Phase specific suppression of neutrophil function in hibernating Syrian hamster.

Hibernation consists of alternating periods of reduced metabolism (torpor) with brief periods of metabolism similar to summer euthermia (arousal). The function of the innate immune system is reduced during hibernation, of which the underlying mechanisms are incompletely understood. Here, we studied neutrophil functionality during hibernation in Syrian hamsters. The inflammatory response to LPS-induced endotoxemia is inhibited in hibernation, partly mediated by reduced IL-6 production in early arousal. Furthermore, neutrophil pathogen binding, phagocytosis and oxidative burst is profoundly reduced in early arousal. Functionality of both summer and early arousal neutrophils was repressed in plasma from early arousal and mixed plasma from early arousal and summer euthermic, but restored by summer euthermic plasma, signifying that a plasma factor in early arousal inhibits TLR-recognition. Identification of the inhibiting factor may offer a target to modulate neutrophil function with relevance to (auto-)inflammatory diseases.

Enhanced bodily states of fear facilitates bias perception of fearful faces.

We investigated whether enhanced interoceptive bodily states of fear would facilitate recognition of the fearful faces. Participants performed an emotional judgment task after a bodily imagery task inside a functional magnetic resonance imaging scanner. In the bodily imagery task, participants were instructed to imagine feeling the bodily sensations of two specific somatotopic patterns: a fear-associated bodily sensation (FBS) or a disgust-associated bodily sensation (DBS). They were shown faces expressing various levels of fearfulness and disgust and instructed to classify the facial expression as fear or disgust. We found a stronger bias favoring the "fearful face" under the congruent FBS condition than under the incongruent DBS condition. The brain response to fearful versus intermediate faces increased in the fronto-insular-temporal network under the FBS condition, but not the DBS condition. The fearful face elicited activity in the anterior cingulate cortex and extrastriate body area under the FBS condition relative to the DBS condition. Furthermore, functional connectivity between the anterior cingulate cortex/extrastriate body area and the fronto-insular-temporal network was modulated according to the specific bodily sensation. Our findings suggest that somatotopic patterns of bodily sensation provide informative access to the collective visceral state in the fear processing via the fronto-insular-temporal network.

Substantia Nigra Abnormalities Provide New Insight on the Neural Mechanisms Underlying the Sleep-Arousal Phase Dysfunctions in Sudden Infant Death Syndrome.

The purpose of this study was to research possible developmental alterations of the substantia nigra (SN) in sudden infant death syndrome (SIDS), a syndrome frequently attributed to arousal failure from sleep. Brain stems of 46 victims of sudden infant death, aged from 1 to about 7 months (4 to 30 postnatal weeks), were investigated. Twenty-six of these cases were diagnosed as SIDS, due to the lack of any pathological finding, while the remaining 20 cases in which the cause of death was determined at autopsy served as controls. Maternal smoking was reported in 77% of SIDS and 10% of controls. Histopathological examination of the SN was done on 5-µm-thick sections of caudal midbrain stained with both hematoxylin-eosin and Klüver-Barrera. Densitometry, immunohistochemistry and histochemistry were applied to highlight the neuronal concentration, the tyrosine hydroxylase (TH) expression, and the presence of neuromelanin (NM) in this structure. Hypoplasia of the pars compacta portion of the SN was observed in 69% of SIDS but never in controls; TH expression was significantly higher in controls than in SIDS; and NM was observed only in 4 infants of the control group but not in SIDS. A significant correlation was found between SIDS, hypoplasia/low neuronal density, low TH expression in the pars compacta, and maternal smoking. Because the SN pars compacta, being the major dopamine brain center, controls many functions, including the sleep-arousal phase, its alterations, especially concurrently with smoking exposure, may contribute to explain the pathogenesis of SIDS that occur in the great part of cases at awakening from sleep.

Early developmental electroencephalography abnormalities, neonatal seizures, and induced spasms in a mouse model of tuberous sclerosis complex.

OBJECTIVE: Tuberous sclerosis complex (TSC) is one of the most common genetic causes of epilepsy. Seizures in TSC typically first present in infancy or early childhood, including focal seizures and infantile spasms. Infantile spasms in TSC are particularly characteristic in its strong responsiveness to vigabatrin. Although a number of mouse models of epilepsy in TSC have been described, there are very limited electroencephalographic (EEG) or seizure data during the preweanling neonatal and infantile-equivalent mouse periods. Tsc1GFAP CKO mice are a well-characterized mouse model of epilepsy in TSC, but whether these mice have seizures during early development has not been documented. The objective of this study was to determine whether preweanling Tsc1GFAP CKO mice have developmental EEG abnormalities or seizures, including spasms. METHODS: Longitudinal video-EEG and electromyographic recordings were performed serially on Tsc1GFAP CKO and control mice from postnatal days 9-21 and analyzed for EEG background abnormalities, sleep-wake vigilance states, and spontaneous seizures. Spasms were also induced with varying doses of N-methyl-D-aspartate (NMDA). RESULTS: The interictal EEG of Tsc1GFAP CKO mice had excessive discontinuity and slowing, suggesting a delayed developmental progression compared with control mice. Tsc1GFAP CKO mice also had increased vigilance state transitions and fragmentation. Tsc1GFAP CKO mice had spontaneous focal seizures in the early neonatal period and a reduced threshold for NMDA-induced spasms, but no spontaneous spasms were observed. SIGNIFICANCE: Neonatal Tsc1GFAP CKO mice recapitulate early developmental aspects of EEG abnormalities, focal seizures, and an increased propensity for spasms. This mouse model may be useful for early mechanistic and therapeutic studies of epileptogenesis in TSC.

Journey towards a personalised medicine approach for OSA: Can a similar approach to adult OSA be applied to paediatric OSA?

The concept of personalised medicine is likely to revolutionise the treatment of adult obstructive sleep apnoea as a result of recent advances in the understanding of disease heterogeneity by identifying clinical phenotypes, pathophysiological endotypes, biomarkers and treatable traits. Children with the condition show a similar level of heterogeneity and paediatric obstructive sleep apnoea would also benefit from a more targeted approach to diagnosis and management. This review aims to summarise the adult literature on the phenotypes and endotypes of obstructive sleep apnoea and assess whether a similar approach may also be suitable to guide the development of new diagnostic and management approaches for paediatric obstructive sleep apnoea.

Distinct temporal integration of noradrenaline signaling by astrocytic second messengers during vigilance.

Astrocytes may function as mediators of the impact of noradrenaline on neuronal function. Activation of glial α1-adrenergic receptors triggers rapid astrocytic Ca2+ elevation and facilitates synaptic plasticity, while activation of ß-adrenergic receptors elevates cAMP levels and modulates memory consolidation. However, the dynamics of these processes in behaving mice remain unexplored, as do the interactions between the distinct second messenger pathways. Here we simultaneously monitored astrocytic Ca2+ and cAMP and demonstrate that astrocytic second messengers are regulated in a temporally distinct manner. In behaving mice, we found that while an abrupt facial air puff triggered transient increases in noradrenaline release and large cytosolic astrocytic Ca2+ elevations, cAMP changes were not detectable. By contrast, repeated aversive stimuli that lead to prolonged periods of vigilance were accompanied by robust noradrenergic axonal activity and gradual sustained cAMP increases. Our findings suggest distinct astrocytic signaling pathways can integrate noradrenergic activity during vigilance states to mediate distinct functions supporting memory.

The Reciprocal Relationship Between Sexual Arousal and Disgust as Evidenced in Automatic Approach-Avoidance Behavior.

Sexual encounters imply exposure to stimuli that in other contexts typically elicit disgust-induced avoidance. To explain why people nevertheless tend to show sexual approach, it has been proposed that heightened sexual arousal may temporarily inhibit disgust. In line with this, studies have found that sexually aroused individuals showed heightened willingness to approach disgusting stimuli. Because automatic processes are critically involved in sexual behaviors, we examined whether the impact of sexual arousal extends to automatic responses to disgust-elicitors. To test the proposed reciprocal relationship between sex and disgust, we also investigated whether disgust reduces automatic sexual approach. In Study 1, 116 female participants (M = age 19.53) were assigned to a sexual arousal or control condition and performed a speeded approach-avoidance task to assess automatic responses to disgusting stimuli. In Study 2, 174 female participants (M = age 22.14) were assigned to a disgust, sexual arousal, or control condition and performed an approach-avoidance task involving both sex and disgust-relevant stimuli. Sexual arousal did not affect automatic responses to disgusting stimuli, and disgust did not influence automatic responses towards sexual stimuli. The reciprocal relationship between sexual arousal and disgust that was previously found for controllable responses did not extend to automatic responses.