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1.
J Clin Sleep Med ; 2024 Oct 04.
Article in English | MEDLINE | ID: mdl-39364956

ABSTRACT

STUDY OBJECTIVES: Arousal burden (AB) is defined as the cumulative duration of arousals during sleep divided by the total sleep time. However, in-depth analysis of AB related to sleep characteristics is lacking. Based on previous studies addressing the arousal index (ArI), we hypothesized that the AB would peak in the supine sleeping position and during non-rapid eye movement stage 1 (N1) and show high variability between scorers. METHODS: Nine expert scorers analyzed polysomnography recordings of 50 participants, the majority with an increased risk for obstructive sleep apnea. AB was calculated in different sleeping positions and sleep stages. A generalized estimating equation was utilized to test the association between AB and sleeping positions, sleep stages, and scorers. The correlation between AB and ArI was tested with Spearman's rank-order correlation. RESULTS: AB significantly differed between sleeping positions (p<0.001). The median AB in the supine sleeping position was 47-62% higher than in the left and right position. The AB significantly differed between the sleep stages (p<0.001); the median AB was more than 200% higher during N1 than during other sleep stages. In addition, the AB differed significantly between scorers (p<0.001) and correlated strongly with ArI (r=0.935, p<0.001). CONCLUSIONS: AB depends on the sleeping position, sleep stage, and scorer as hypothesized. AB behaved similarly as the ArI, but the high variability in the ABs between scorers indicates a potential limitation caused by subjective manual scoring. Thus, the development of more accurate techniques for scoring arousals is required before AB can be reliably utilized.

3.
Sleep Med ; 124: 299-307, 2024 Sep 29.
Article in English | MEDLINE | ID: mdl-39366085

ABSTRACT

Adolescents devote a significant portion of their time to smartphone usage, often engaging in social media activities. Social media use has previously been linked to diminished sleep quality and reduced sleep durations in correlational studies. In this experimental study, we aimed to investigate the influence of pre-sleep social media use on memory consolidation, subjective arousal and objectively assessed sleep quality in adolescents. We compared the social media condition to two reading conditions, one involving reading a book on a smartphone and the other reading from a physical book in a within-subjects design. Twenty participants between 12 and 14 years engaged in these activities for 45 min before bedtime. Contrary to our expectations, the results indicated that pre-sleep social media use did not have a discernible impact on sleep quality, pre-sleep arousal or memory consolidation. All assessed sleep measures remained consistent across the three conditions. Subjectively, the social media condition was rated less thrilling than the reading conditions. This suggests that, within the confines of this experiment, pre-sleep social media exposure did not significantly disrupt adolescents' sleep or their ability to consolidate memories during sleep. This deviation from previous correlational studies might be explained by a possible impact of mental health factors on media consumption and sleep or the fact that contrary to their daily routines participants had to sleep after our intervention and could not continue to engage in their activities. This highlights the need for further investigations into the complexities of this interaction.

4.
Sleep Med ; 124: 396-403, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39395262

ABSTRACT

STUDY OBJECTIVES: The respiratory effort-related arousal (RERA) has been combined with apneas and hypopneas into the respiratory disturbance index (RDI). RERAs are characterized by ≥ 10 s of increasing upper airway effort terminating in arousal without meeting hypopnea criteria. The recent change to hypopnea definitions now includes a ≥30 % reduction in airflow for 10 s with EITHER a 3 % oxygen desaturation OR an arousal. Consequently, many events previously categorized as RERAs will now be included in the 3 % hypopneas, likely reducing the number of events scored as RERAs. We hypothesized that the 3 % apnea-hypopnea index (3%AHI) would approximate the 4%RDI, with the number of 3 % RERAs being negligible. RESEARCH QUESTION: How does the transition from the 4 % to the 3 % hypopnea rules impact the significance of RERAs in clinical practice, and how we should relate the AHI and RDI using the different hypopnea rules? METHODS: We prospectively collected 76 consecutive polysomnography results in 4 adult age groups. We re-scored the respiratory events utilizing both the 3 % and the 4 % hypopnea rules and compared the outcomes. RESULTS: Among 76 diagnostic studies (mean age 47.5 years, males 47.4 %), the 3 % RERA index [0.8 (0.0, 3.1)] [median (Q1, Q3)] was significantly lower than the 4 % RERA index [3.5 (1.0, 7.3)]. The 3%AHI was 3.07 ± 9.23 (mean ± SD) higher than the 4%RDI (p = 0.005). The 3%AHI was 8.63 ± 8.86 higher than the 4%AHI in all age groups (p < 0.001). This was mainly due to an increased hypopnea index (+8.51 ± 9.03, p < 0.001). In patients with obstructive sleep apnea (OSA), the 3%RERA contributes 4.3 % to the 3%RDI, while the 4%RERA contributes 27.7 % to the 4%RDI. INTERPRETATIONS: Both 3%RDI and 3%AHI are higher than the 4%RDI, primarily due to identification of more hypopnea events, resulting in more patients being classified as having OSA. This change in criteria complicates the comparison of hypopnea and RERA contributions between sleep studies scored using the different hypopnea rules.

5.
Article in English | MEDLINE | ID: mdl-39379767

ABSTRACT

Everyday experiences often overlap, challenging our ability to maintain distinct episodic memories. One way to resolve such interference is by exaggerating subtle differences between remembered events, a phenomenon known as memory repulsion. Here, we tested whether repulsion is influenced by emotional arousal, when resolving memory interference is perhaps most needed. We adapted an existing paradigm in which participants repeatedly studied object-face associations. Participants studied two different-colored versions of each object: a to-be-tested "target" and its not-to-be-tested "competitor" pair mate. The level of interference between target and competitor pair mates was manipulated by making the object colors either highly similar or less similar, depending on the participant group. To manipulate arousal, the competitor object-face associations were preceded by either a neutral tone or an aversive and arousing burst of white noise. Memory distortion for the color of the target objects was tested after each study round to examine whether memory distortions emerge after learning. We found that participants with greater sound-induced pupil dilations, an index of physiological arousal, showed greater memory attraction of target colors towards highly similar competitor colors. Greater memory attraction was also correlated with greater memory interference in the last round of learning. Additionally, individuals who self-reported higher trait anxiety showed greater memory attraction when one of the overlapping memories was associated with something aversive. Our findings suggest that memories of similar neutral and arousing events may blur together after repeated exposures, especially in individuals who show higher arousal responses and symptoms of anxiety.

6.
Psicol Reflex Crit ; 37(1): 41, 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39327361

ABSTRACT

BACKGROUND: The Self-Assessment Manikin (SAM), a pictorial scale for the measurement of pleasure and arousal dimensions of emotions, is one of the most applied tools in the emotion research field. OBJECTIVE: We present a detailed description of a remote method to collect affective ratings in response to pictures by using the SAM scale. METHODS: To empirically validate our remote method, we conducted a study using a digitized version of the SAM scale and delivered online didactic instructions that followed the normative rating procedure for the International Affective Picture System (IAPS) to the participants. We presented 70 pictures from the IAPS and an additional set of 22 food pictures to the participants. RESULTS: We found strong correlations between the ratings of IAPS pictures obtained in our sample and those reported by North American and Brazilian participants in previous in-person studies that applied the same pictures and methodology. We were also able to obtain an additional standardized set of food pictures. CONCLUSION: The protocols described here may be useful for researchers interested in collecting remotely valid and reliable affecting ratings.

7.
PNAS Nexus ; 3(9): pgae370, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39282005

ABSTRACT

The skin conductance (SC) and eye tracking data are two potential arousal-related psychophysiological signals that can serve as the interoceptive unconditioned response to aversive stimuli (e.g. electric shocks). The current research investigates the sensitivity of these signals in detecting mild electric shock by decoding the hidden arousal and interoceptive awareness (IA) states. While well-established frameworks exist to decode the arousal state from the SC signal, there is a lack of a systematic approach that decodes the IA state from pupillometry and eye gaze measurements. We extract the physiological-based features from eye tracking data to recover the IA-related neural activity. Employing a Bayesian filtering framework, we decode the IA state in fear conditioning and extinction experiments where mild electric shock is used. We independently decode the underlying arousal state using binary and marked point process (MPP) observations derived from concurrently collected SC data. Eight of 11 subjects present a significantly (P-value < 0.001 ) higher IA state in trials that were always accompanied by electric shock ( CS + US + ) compared to trials that were never accompanied by electric shock ( CS - ). According to the decoded SC-based arousal state, only five (binary observation) and four (MPP observation) subjects present a significantly higher arousal state in CS + US + trials than CS - trials. In conclusion, the decoded hidden brain state from eye tracking data better agrees with the presented mild stimuli. Tracking IA state from eye tracking data can lead to the development of contactless monitors for neuropsychiatric and neurodegenerative disorders.

8.
Diagnostics (Basel) ; 14(18)2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39335756

ABSTRACT

Introduction: Accurately detecting arousal events during sleep is essential for evaluating sleep quality and diagnosing sleep disorders, such as sleep apnea/hypopnea syndrome. While the American Academy of Sleep Medicine guidelines associate arousal events with electroencephalogram (EEG) signal variations, EEGs are often not recorded during home sleep testing (HST) using wearable devices or smartphone applications. Objectives: The primary objective of this study was to explore the potential of alternatively relying on combinations of easily measurable physiological signals during HST for arousal detection where EEGs are not recorded. Methods: We conducted a data-driven retrospective study following an incremental device-agnostic analysis approach, where we simulated a limited-channel setting using polysomnography data and used deep learning to automate the detection task. During the analysis, we tested multiple signal combinations to evaluate their potential effectiveness. We trained and evaluated the model on the Multi-Ethnic Study of Atherosclerosis dataset. Results: The results demonstrated that combining multiple signals significantly improved performance compared with single-input signal models. Notably, combining thoracic effort, heart rate, and a wake/sleep indicator signal achieved competitive performance compared with the state-of-the-art DeepCAD model using electrocardiogram as input with an average precision of 61.59% and an average recall of 56.46% across the test records. Conclusions: This study demonstrated the potential of combining easy-to-record HST signals to characterize the autonomic markers of arousal better. It provides valuable insights to HST device designers on signals that improve EEG-free arousal detection.

9.
Behav Sci (Basel) ; 14(9)2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39335985

ABSTRACT

Sexual satisfaction is an important dimension of sexual health. Despite there being evidence about its relations with sexual arousal, this association has not been addressed considering arousal as a trait and as a state. Therefore, the goal of this laboratory study was to examine, in young women with different levels of sexual satisfaction in their relationships, sexual arousal as a trait (i.e., propensity for sexual excitation/inhibition) and as a state (i.e., genital response and self-reported sexual arousal to a video with explicit sexual content). The sample was composed of 45 Spanish heterosexual women with a partner, from 18 to 25 years old. In the first phase, we evaluated the propensity for sexual inhibition/excitation and sexual satisfaction of the participants. In the second phase-in the context of a sexuality laboratory-the vaginal pulse amplitude, the rating of sexual arousal, and the rating of genital sensations were evaluated. The participants, distributed in three groups with different levels of sexual satisfaction (p < 0.001), were compared based on the different measures of sexual arousal. The results indicated that the group with lower sexual satisfaction, compared to the group with higher sexual satisfaction, reported more sexual inhibition due to the threat of performance failure (p = 0.011) and due to the threat of performance consequences (p = 0.038). However, no significant differences in sexual arousal status were found between the three groups. In conclusion, the negative association between sexual satisfaction and propensity for sexual inhibition in young women with a partner is supported, but not the positive association between trait/state sexual arousal and sexual satisfaction.

10.
Behav Sci (Basel) ; 14(9)2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39336009

ABSTRACT

Social media use is associated with poor sleep outcomes. We aimed to extend previous research by examining how measures of social media use would affect two sleep characteristics: sleep quality and insomnia symptoms. In addition, we tested a serial mediation model linking social media use to sleep through increases in negative social comparison and pre-sleep cognitive arousal. Participants were 830 emerging adults (ages 18-30) who were recruited for an online survey study in February 2024. The sample was 63.1% female, with an average age of 24. We examined three measures of social media use: duration (minutes of daily use), frequency (number of weekly visits to social media platforms), and emotional investment (attachment to and integration of social media into daily life). Consistent with our hypothesis, greater emotional investment in social media and more frequent social media use were associated with poorer sleep quality and greater insomnia severity. We also found evidence supporting our hypothesized serial mediation model: emotional investment in social media and more frequent social media use were associated with increased negative social comparison, which subsequently increased pre-sleep cognitive arousal, which then led to poorer sleep outcomes. Our findings suggest that negative social comparison and pre-sleep cognitive arousal are important mechanisms linking social media use to poor sleep outcomes. Future studies should aim to test this serial mediation model using longitudinal data and experimental methods.

11.
Behav Sci (Basel) ; 14(9)2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39336024

ABSTRACT

(1) Background: This study examines the role of subjective anxiety (mathematics and spatial anxiety), along with physiological responses, in mathematics or math and mental rotation performance in 131 German primary school students (65 girls, 66 boys; Mean age = 8.73 years). (2) Method: Students' preference for math vs. German and their subjective anxiety were assessed using standardized questionnaires. Emotional reactivity was measured using the Galvanic Skin Response (GSR). Math performance was evaluated via percentage scored and completion times on number line estimation, word problems, and missing terms tasks. Spatial skills were assessed using a novel mental rotation task (nMRT) incorporating gender-congruent and -neutral stimuli. (3) Results: Girls outperformed boys on percentage scored on the math task but took longer to complete this. No gender differences were found in performance on the nMRT. Girls demonstrated higher math anxiety and were less likely to prefer math over German. Math anxiety predicted math scores and accuracy on the nMRT while gender predicted math performance and mental rotation response time. Subject preference was associated with longer completion times and emotional reactivity with longer response times. Girls' preference for math and lower emotional reactivity was linked to shorter completion times, while lower math anxiety predicted higher scores. In contrast, these factors did not affect boys' math performance. Additionally, subjective anxiety, emotional reactivity, or subject preference did not impact spatial performance for either gender. (4) Conclusions: Supporting mathematical self-efficacy and emotional regulation, especially in girls, is crucial for enhancing STEM outcomes in primary education. Gender-fair assessment in mental rotation reveals equitable spatial performance and reduces the impact of anxiety.

12.
J Clin Med ; 13(18)2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39336964

ABSTRACT

Background: Increasing research data suggest that the dysfunction of emotional brain systems may be an important contributor to the pathophysiology of schizophrenia. However, contemporary psychopathology consistently underestimates the role of emotions in the phenomenology of the disease. Psychotic arousal (PA) is a conceptually defined psychopathological construct aiming to portray the experiential emotional state of acute psychosis. The concept provides an explanatory model for the emergence of psychosis, and the formation and maintenance of delusions based on neurobiological models on the formation of core consciousness and subjectivity. This is the first exploratory study of the major assumptions, endorsed in the project summarized as follows: (1) psychotic arousal is a discrete state, eligible for investigation; (2) abnormal experiential feelings are an integral part of this state; and (3) the state is responsive to antipsychotic intervention during the first weeks of treatment. Methods: We developed the Psychotic Arousal Scale (PAS) accordingly, explored its first psychometric properties and tested its relation to other psychopathological measures. Fifty-five acute schizophrenia patients were evaluated with the PAS, the Positive and Negative Syndrome Scale, the Brown Assessment of Beliefs Scale, the Hamilton Anxiety Scale, and the Calgary Depression Scale. Cronbach α coefficients, t-test analysis, correlations and mixed linear regression models were applied for testing the internal reliability of the scale, associations between parameters and sensitivity to change in three time periods during therapeutic intervention. Results: The results of the study support that (PA) is eligible for investigation as a discrete psychopathological state. Abnormal experiential feelings are an integral part of this state, presenting high affinity with other affective measures; their degree of severity relates to the delusions' conviction and are amenable to antipsychotics early in treatment during the acute psychotic episode. Conclusions: The findings of this exploratory study are connotative of the presence of an emotional arousal permeated by abnormal experiential feelings during acute psychosis, largely overlooked by contemporary psychopathology.

13.
World J Mens Health ; 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39344114

ABSTRACT

PURPOSE: Twenty five years have passed since the first national survey on erectile dysfunction (ED) in Japan. The Japanese Society for Sexual Medicine conducted a nationwide survey on the actual status of sexual function targeting men over 20 years old in Japan using validated questionnaires commonly used in clinical practice. MATERIALS AND METHODS: Japanese men aged 20 to 79 years participated in our online epidemiological study on sexual dysfunction. Erectile status was assessed by direct questioning and specific questionnaires. Risk factors and frequencies of sexual intercourse, masturbation, nocturnal erections, and feeling sexual desire were assessed. The prevalence of these risk factors was compared between men with and without ED. Prevalence and frequencies were calculated for each 5-year age group. Main outcomes were the prevalence and number of patients with ED and simultaneous evaluation of age-related variations. RESULTS: Direct questioning of the men revealed that 13.0% felt troubled by ED. Although 81.0% of them had at least some ED symptoms based on a Sexual Health Inventory For Men score of ≤21, the prevalence of men with ED by Erection Hardness Score (EHS), the most appropriate questionnaire for Japanese with low sexual activity, was 30.9%, indicating that 14,012,596 men have ED. Most risk factors were related with ED, whereas frequencies of sexual intercourse, masturbation, nocturnal erections, and feeling sexual desire were affected by aging. However, the low frequency of these factors in the young generation was surprising. CONCLUSIONS: The EHS-based assessment revealed a prevalence of ED of 30.9%, which affected approximately 14 million men, and that the sexual desire, erection stiffness, orgasms, and satisfaction were lower than expected in young Japanese men, especially those aged 20 to 24 years, although those factors tended to worsen with aging. We believe that these findings actually reveal the current sexual status of men in Japan.

14.
Curr Biol ; 2024 Sep 07.
Article in English | MEDLINE | ID: mdl-39265569

ABSTRACT

Sleeping animals can be woken up rapidly by external threat signals, which is an essential defense mechanism for survival. However, neuronal circuits underlying the fast transmission of sensory signals for this process remain unclear. Here, we report in mice that alerting sound can induce rapid awakening within hundreds of milliseconds and that glutamatergic neurons in the pontine central gray (PCG) play an important role in this process. These neurons exhibit higher sensitivity to auditory stimuli in sleep than wakefulness. Suppressing these neurons results in reduced sound-induced awakening and increased sleep in intrinsic sleep/wake cycles, whereas their activation induces ultra-fast awakening from sleep and accelerates awakening from anesthesia. Additionally, the sound-induced awakening can be attributed to the propagation of auditory signals from the PCG to multiple arousal-related regions, including the mediodorsal thalamus, lateral hypothalamus, and ventral tegmental area. Thus, the PCG serves as an essential distribution center to orchestrate a global auditory network to promote rapid awakening.

15.
bioRxiv ; 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39345640

ABSTRACT

Subcortical arousal systems are known to play a key role in controlling sustained changes in attention and conscious awareness. Recent studies indicate that these systems have a major influence on short-term dynamic modulation of visual attention, but their role across sensory modalities is not fully understood. In this study, we investigated shared subcortical arousal systems across sensory modalities during transient changes in attention using block and event-related fMRI paradigms. We analyzed massive publicly available fMRI datasets collected while 1,561 participants performed visual, auditory, tactile, and taste perception tasks. Our analyses revealed a shared circuit of subcortical arousal systems exhibiting early transient increases in activity in midbrain reticular formation and central thalamus across perceptual modalities, as well as less consistent increases in pons, hypothalamus, basal forebrain, and basal ganglia. Identifying these networks is critical for understanding mechanisms of normal attention and consciousness and may help facilitate subcortical targeting for therapeutic neuromodulation.

16.
J Med Signals Sens ; 14: 20, 2024.
Article in English | MEDLINE | ID: mdl-39234591

ABSTRACT

Background: This study explores a novel approach to detecting arousal levels through the analysis of electroencephalography (EEG) signals. Leveraging the Faller database with data from 18 healthy participants, we employ a 64-channel EEG system. Methods: The approach we employ entails the extraction of ten frequency characteristics from every channel, culminating in a feature vector of 640 dimensions for each signal instance. To enhance classification accuracy, we employ a genetic algorithm for feature selection, treating it as a multiobjective optimization task. The approach utilizes fast bit hopping for efficiency, overcoming traditional bit-string limitations. A hybrid operator expedites algorithm convergence, and a solution selection strategy identifies the most suitable feature subset. Results: Experimental results demonstrate the method's effectiveness in detecting arousal levels across diverse states, with improvements in accuracy, sensitivity, and specificity. In scenario one, the proposed method achieves an average accuracy, sensitivity, and specificity of 93.11%, 98.37%, and 99.14%, respectively. In scenario two, the averages stand at 81.35%, 88.65%, and 84.64%. Conclusions: The obtained results indicate that the proposed method has a high capability of detecting arousal levels in different scenarios. In addition, the advantage of employing the proposed feature reduction method has been demonstrated.

17.
Psychiatry Res ; 342: 116165, 2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39316999

ABSTRACT

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.

18.
CNS Neurosci Ther ; 30(9): e70047, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39317457

ABSTRACT

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Subject(s)
Anesthetics, Inhalation , Arousal , GABAergic Neurons , Neural Pathways , Periaqueductal Gray , Sevoflurane , Animals , Sevoflurane/pharmacology , Periaqueductal Gray/drug effects , Periaqueductal Gray/metabolism , GABAergic Neurons/drug effects , GABAergic Neurons/physiology , Mice , Anesthetics, Inhalation/pharmacology , Male , Arousal/drug effects , Arousal/physiology , Neural Pathways/drug effects , Neural Pathways/physiology , Mice, Inbred C57BL , Hypothalamic Area, Lateral/drug effects , Hypothalamic Area, Lateral/physiology , Mice, Transgenic , Optogenetics , Hypothalamus/drug effects , Hypothalamus/metabolism
19.
J Neurochem ; 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39233365

ABSTRACT

Fear-related psychopathologies, such as post-traumatic stress disorder, are linked to dysfunction in neural circuits that govern fear memory and arousal. The lateral hypothalamus (LH) and zona incerta (ZI) regulate fear, but our understanding of the precise neural circuits and cell types involved remains limited. Here, we examined the role of relaxin family peptide receptor 3 (RXFP3) expressing cells in the LH/ZI in conditioned fear expression and general arousal in male RXFP3-Cre mice. We found that LH/ZI RXFP3+ (LH/ZIRXFP3) cells projected strongly to fear learning, stress, and arousal centres, notably, the periaqueductal grey, lateral habenula, and nucleus reuniens. These cells do not express hypocretin/orexin or melanin-concentrating hormone but display putative efferent connectivity with LH hypocretin/orexin+ neurons and dopaminergic A13 cells. Following Pavlovian fear conditioning, chemogenetically activating LH/ZIRXFP3 cells reduced fear expression (freezing) overall but also induced jumping behaviour and increased locomotor activity. Therefore, the decreased freezing was more likely to reflect enhanced arousal rather than reduced fear. Indeed, stimulating these cells produced distinct patterns of coactivation between several motor, stress, and arousal regions, as measured by Fos expression. These results suggest that activating LH/ZIRXFP3 cells generates brain-wide activation patterns that augment behavioural arousal.

20.
Front Psychiatry ; 15: 1415135, 2024.
Article in English | MEDLINE | ID: mdl-39247616

ABSTRACT

Introduction: While abnormal responses to threat, including overgeneralization to conditioned fear, have been postulated to play a critical role in pathological anxiety, the relevance of previous findings to social anxiety disorder (SAD) is unclear. We investigated conditioned and generalized fear responses in patients with SAD using socially relevant stimuli. Methods: A total of 26 patients with SAD and 25 healthy controls participated in a fear conditioning and generalization paradigm consisting of two neutral faces as conditioned stimuli (CS+ or CS-) and an angry face with contemptuous comments as unconditioned stimuli. Eight morphed faces of two conditioned stimuli in each continuum were given to test generalization. Behavioral data and physiological responses were acquired. Results: Successful conditioning was observed in the risk ratings for both groups, while only a marginal indication of conditioning was noted in physiological measures. During the generalization phase, patients rated the risk higher than CS- when the stimuli close to CS- contained a portion of CS+ features. Larger skin conductance responses to this stimulus were linked to higher fear of negative evaluation. In addition, patients spent a longer time evaluating safe and ambiguous stimuli than healthy controls and exhibited consistently high levels of subjective arousal. Discussion: Taken together, our findings suggest that SAD patients may exhibit a tendency towards overgeneralization of fear responses and show distinct patterns in processing generalized threat stimuli compared to healthy controls. Even though overgeneralization was not evident in physiological measures, it is necessary to consider this behavioral characteristic in the clinical management of patients with SAD.

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