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1.
Cognition ; 251: 105908, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39094255

RESUMEN

Retrieval-induced forgetting (RIF) experiments show that the act of retrieving some recently encoded items from a given conceptual category leads to greater forgetting of competing items from that same category. However, RIF studies using emotional stimuli have produced mixed results, perhaps due to the reinstatement of arousal or negative affect during retrieval practice. To induce forgetting of negative episodic memories more indirectly, we examined if retrieving neutral semantic memories leads to RIF of related negative memories. In two experiments, participants studied eight categorized lists comprised of an equal number of negative and neutral words (Experiment 1) or neutral words preceded by neutral or negative images (Experiment 2). To avoid re-exposing individuals to negative material during retrieval practice, participants then performed a semantic memory retrieval task in which they generated (i.e., completed word-stems for) new neutral words from half of the studied categories. We found that semantic retrieval, or word generation, induced forgetting of recently studied words irrespective of their emotional valence or original emotional context. Additionally, across both experiments, less successful word generation was associated with stronger RIF effects. In Experiment 2, the magnitude of RIF was also correlated with higher subjective ratings of retrieval effort during word generation. Together, these results suggest that even when retrieving neutral semantic memories, effortful retrieval may enhance inhibitory processes that lead to forgetting of both neutral and negative episodic memories.

2.
Autism Res ; 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39087850

RESUMEN

Different empathic responses are often reported in autism but remain controversial. To investigate which component of empathy is most affected by autism, we examined the affective, cognitive, and motivational components of empathy in 25 5- to 8-year-old autistic and 27 neurotypical children. Participants were presented with visual stimuli depicting people's limbs in painful or nonpainful situations while their eye movements, pupillary responses, and verbal ratings of pain intensity and empathic concern were recorded. The results indicate an emotional overarousal and reduced empathic concern to others' pain in autism. Compared with neurotypical children, autistic children displayed larger pupil dilation accompanied by attentional avoidance to others' pain. Moreover, even though autistic children rated others in painful situations as painful, they felt less sorry than neurotypical children. Interestingly, autistic children felt more sorry in nonpainful situations compared with neurotypical children. These findings demonstrated an emotional overarousal in response to others' pain in autistic children, and provide important implications for clinical practice aiming to promote socio-emotional understanding in autistic children.

3.
Brain Struct Funct ; 2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39096390

RESUMEN

Emotional arousal is caused by the activity of two parallel ascending systems targeting mostly the subcortical limbic regions and the prefrontal cortex. The aversive, negative arousal system is initiated by the activity of the mesolimbic cholinergic system and the hedonic, appetitive, arousal is initiated by the activity of the mesolimbic dopaminergic system. Both ascending projections have a diffused nature and arise from the rostral, tegmental part of the brain reticular activating system. The mesolimbic cholinergic system originates in the laterodorsal tegmental nucleus and the mesolimbic dopaminergic system in the ventral tegmental area. Cholinergic and dopaminergic arousal systems have converging input to the medial prefrontal cortex. The arousal system can modulate cortical EEG with alpha rhythms, which enhance synaptic strength as shown by an increase in long-term potentiation (LTP), whereas delta frequencies are associated with decreased arousal and a decrease in synaptic strength as shown by an increase in long-term depotentiation (LTD). It is postulated that the medial prefrontal cortex is an adaptable node with decision making capability and may control the switch between positive and negative affect and is responsible for modifying or changing emotional state and its expression.

4.
bioRxiv ; 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38948871

RESUMEN

Matching arousal level to the motor activity of an animal is important for efficiently allocating cognitive resources and metabolic supply in response to behavioral demands, but how the brain coordinates changes in arousal and wakefulness in response to motor activity remains an unclear phenomenon. We hypothesized that the locus coeruleus (LC), as the primary source of cortical norepinephrine (NE) and promoter of cortical and sympathetic arousal, is well-positioned to mediate movement-arousal coupling. Here, using a combination of physiological recordings, fiber photometry, optogenetics, and behavioral tracking, we show that the LCNE activation is tightly coupled to the return of organized movements during waking from an anesthetized state. Moreover, in an awake animal, movement initiations are coupled to LCNE activation, while movement arrests, to LCNE deactivation. We also report that LCNE activity covaries with the depth of anesthesia and that LCNE photoactivation leads to sympathetic activation, consistent with its role in mediating increased arousal. Together, these studies reveal a more nuanced, modulatory role that LCNE plays in coordinating movement and arousal.

5.
J Sleep Res ; : e14275, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38952031

RESUMEN

Sleepwalking and related parasomnias are thought to result from incomplete awakenings out of non-rapid eye movement (non-REM) sleep. Non-REM parasomnia behaviours have been described as unconscious and automatic, or related to vivid, dream-like conscious experiences. Similarly, some observations have suggested that patients are unresponsive during episodes, while others that they can interact with their surroundings. To better grasp and characterise the full spectrum of consciousness and environmental (dis)connection associated with behavioural episodes, 35 adult patients with non-REM sleep parasomnias were interviewed in-depth about their experiences. The level of consciousness during parasomnia episodes was reported to be variable both within and between individuals, ranging from minimal or absent consciousness and largely automatic behaviours (frequently/always present in 36% of patients) to preserved conscious experiences characterised by delusional thinking to varying degrees of specificity (65%), often about impending danger, variably formed, uni- or multisensory hallucinations (53%), impaired insight (77%), negative emotions (75%), and variable, but often pronounced, amnesia (30%). Patients described their experiences as a dream scene during which they felt awake ("awake dreaming"). The surroundings were either realistically perceived, misinterpreted (in the form of perceptual illusions or misidentifications of people), or entirely hallucinated as a function of the prevailing delusion. These observations suggest that the level of consciousness, amnesia and sensory disconnection during non-REM parasomnia episodes is variable and graded. In their full-fledged expression, non-REM parasomnia experiences feature several core features of dreams. They therefore represent a valuable model for the study of consciousness, sleep-related sensory disconnection and dreaming.

6.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(3): 402-408, 2024 Jun.
Artículo en Chino | MEDLINE | ID: mdl-38953264

RESUMEN

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.


Asunto(s)
Nivel de Alerta , Corteza Prefrontal , Área Tegmental Ventral , Corteza Prefrontal/fisiología , Área Tegmental Ventral/fisiología , Nivel de Alerta/fisiología , Humanos , Animales , Vías Nerviosas/fisiología
7.
Front Neurosci ; 18: 1406814, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38962177

RESUMEN

Introduction: Decoding an individual's hidden brain states in responses to musical stimuli under various cognitive loads can unleash the potential of developing a non-invasive closed-loop brain-machine interface (CLBMI). To perform a pilot study and investigate the brain response in the context of CLBMI, we collect multimodal physiological signals and behavioral data within the working memory experiment in the presence of personalized musical stimuli. Methods: Participants perform a working memory experiment called the n-back task in the presence of calming music and exciting music. Utilizing the skin conductance signal and behavioral data, we decode the brain's cognitive arousal and performance states, respectively. We determine the association of oxygenated hemoglobin (HbO) data with performance state. Furthermore, we evaluate the total hemoglobin (HbT) signal energy over each music session. Results: A relatively low arousal variation was observed with respect to task difficulty, while the arousal baseline changes considerably with respect to the type of music. Overall, the performance index is enhanced within the exciting session. The highest positive correlation between the HbO concentration and performance was observed within the higher cognitive loads (3-back task) for all of the participants. Also, the HbT signal energy peak occurs within the exciting session. Discussion: Findings may underline the potential of using music as an intervention to regulate the brain cognitive states. Additionally, the experiment provides a diverse array of data encompassing multiple physiological signals that can be used in the brain state decoder paradigm to shed light on the human-in-the-loop experiments and understand the network-level mechanisms of auditory stimulation.

8.
Br J Anaesth ; 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38965013

RESUMEN

BACKGROUND: Dopaminergic psychostimulants can restore arousal in anaesthetised animals, and dopaminergic signalling contributes to hippocampal-dependent memory formation. We tested the hypothesis that dopaminergic psychostimulants can antagonise the amnestic effects of isoflurane on visuospatial working memory. METHODS: Sixteen adult Sprague-Dawley rats were trained on a trial-unique nonmatching-to-location (TUNL) task which assessed the ability to identify a novel touchscreen location after a fixed delay. Once trained, the effects of low-dose isoflurane (0.3 vol%) on task performance and activity, assessed by infrared beam breaks, were assessed. We attempted to rescue deficits in performance and activity with a dopamine D1 receptor agonist (chloro-APB), a noradrenergic reuptake inhibitor (atomoxetine), and a mixed dopamine/norepinephrine releasing agent (dextroamphetamine). Anaesthetic induction, emergence, and recovery from anaesthesia were also investigated. RESULTS: Low-dose isoflurane impaired working memory in a sex-independent and intra-trial delay-independent manner as assessed by task performance, and caused an overall reduction in activity. Administration of chloro-APB, atomoxetine, or dextroamphetamine did not restore visuospatial working memory, but chloro-APB and dextroamphetamine recovered arousal to levels observed in the baseline awake state. Performance did not differ between induction and emergence. Animals recovered to baseline performance within 15 min of discontinuing isoflurane. CONCLUSIONS: Low-dose isoflurane impairs visuospatial working memory in a nondurable and delay-independent manner that potentially implicates non-hippocampal structures in isoflurane-induced memory deficits. Dopaminergic psychostimulants counteracted sedation but did not reverse memory impairments, suggesting that isoflurane-induced amnesia and isoflurane-induced sedation have distinct underlying mechanisms that can be antagonised independently.

9.
Behav Res Ther ; 180: 104571, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-39084003

RESUMEN

Given the bidirectional association between psychopathology and relationship distress, an in-depth understanding of couples' interaction processes that contribute to psychopathology is needed. This study examined the interpersonal dynamics of vocally-encoded emotional arousal (fundamental frequency, f0) during couple conversations and their associations with depressive symptoms, anxiety symptoms, and relationship distress. Data from eight samples were pooled (N = 404 couples) to examine (a) overall trajectories of f0 across the interaction and (b) moment-by-moment intraindividual changes in and interpersonal reactivity to partners' f0. Multilevel growth models and repeated-measures actor-partner interdependence models demonstrated that individuals with more severe depression showed more synchronizing reactivity to their partners' f0 on a moment-by-moment basis, and their overall baseline level of f0 was lower. More severe relationship distress was associated with more steeply increasing trajectories of f0 and with greater synchronizing reactivity to partners' f0. Relative differences in depressive symptoms between the two members of a couple were associated with interpersonal dynamics of f0 as well. There were no associations with anxiety symptoms. Thus, depressive symptoms were associated with characteristic interpersonal dynamics of vocally-encoded emotional arousal; yet, most consistent associations emerged for relationship distress, which future studies on individual psychopathology should take into account.

10.
J Psychopharmacol ; 38(7): 581-596, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39041250

RESUMEN

Pramipexole, a D2/D3 dopamine receptor agonist, is used to treat the motor symptoms of Parkinson's disease, caused by degeneration of the dopaminergic nigrostriatal pathway. There are three paradoxes associated with its mode of action. Firstly, stimulation of D2/D3 receptors leads to neuronal inhibition, although pramipexole does not inhibit but promotes some dopamine-modulated functions, such as locomotion and reinforcement. Secondly, another dopamine-modulated function, arousal, is not promoted but inhibited by pramipexole, leading to sedation. Thirdly, pramipexole-evoked sedation is associated with an increase in pupil diameter, although sedation is expected to cause pupil constriction. To resolve these paradoxes, the path from stimulation of D2/D3 receptors to the modification of dopamine-modulated functions has been tracked. The functions considered are modulated by midbrain dopaminergic nuclei: locomotion - substantia nigra pars compacta (SNc), reinforcement/motivation - ventral tegmental area (VTA), sympathetic activity (as reflected in pupil function) - VTA; arousal - ventral periaqueductal grey (vPAG), with contributions from VTA and SNc. The application of genetics-based molecular techniques (optogenetics and chemogenetics) has enabled tracing the chains of neurones from the dopaminergic nuclei to their final targets executing the functions. The functional neuronal circuits linked to the D2/D3 receptors in the dorsal and ventral striata, stimulated by inputs from SNc and VTA, respectively, may explain how neuronal inhibition induced by pramipexole is translated into the promotion of locomotion, reinforcement/motivation and sympathetic activity. As the vPAG may increase arousal mainly by stimulating cortical D1 dopamine receptors, pramipexole would stimulate only presynaptic D2/D3 receptors on vPAG neurones, curtailing their activity and leading to sedation.


Asunto(s)
Agonistas de Dopamina , Dopamina , Pramipexol , Receptores de Dopamina D2 , Receptores de Dopamina D3 , Pramipexol/farmacología , Animales , Humanos , Agonistas de Dopamina/farmacología , Receptores de Dopamina D3/metabolismo , Receptores de Dopamina D3/agonistas , Receptores de Dopamina D3/efectos de los fármacos , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D2/efectos de los fármacos , Dopamina/metabolismo , Benzotiazoles/farmacología , Locomoción/efectos de los fármacos , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/metabolismo , Nivel de Alerta/efectos de los fármacos
11.
Trends Hear ; 28: 23312165241258056, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39053892

RESUMEN

This study investigated the morphology of the functional near-infrared spectroscopy (fNIRS) response to speech sounds measured from 16 sleeping infants and how it changes with repeated stimulus presentation. We observed a positive peak followed by a wide negative trough, with the latter being most evident in early epochs. We argue that the overall response morphology captures the effects of two simultaneous, but independent, response mechanisms that are both activated at the stimulus onset: one being the obligatory response to a sound stimulus by the auditory system, and the other being a neural suppression effect induced by the arousal system. Because the two effects behave differently with repeated epochs, it is possible to mathematically separate them and use fNIRS to study factors that affect the development and activation of the arousal system in infants. The results also imply that standard fNIRS analysis techniques need to be adjusted to take into account the possibilities of multiple simultaneous brain systems being activated and that the response to a stimulus is not necessarily stationary.


Asunto(s)
Estimulación Acústica , Nivel de Alerta , Sueño , Espectroscopía Infrarroja Corta , Humanos , Espectroscopía Infrarroja Corta/métodos , Estimulación Acústica/métodos , Lactante , Sueño/fisiología , Femenino , Masculino , Nivel de Alerta/fisiología , Percepción del Habla/fisiología , Corteza Auditiva/fisiología , Corteza Auditiva/diagnóstico por imagen , Vías Auditivas/fisiología , Mapeo Encefálico/métodos , Factores de Tiempo , Factores de Edad , Oxihemoglobinas/metabolismo
12.
eNeuro ; 11(7)2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39029953

RESUMEN

Perceptual decisions are often accompanied by a feeling of decision confidence. Where the parietal cortex is known for its crucial role in shaping such perceptual decisions, metacognitive evaluations are thought to additionally rely on the (pre)frontal cortex. Because of this supposed neural differentiation between these processes, perceptual and metacognitive decisions may be divergently affected by changes in internal (e.g., attention, arousal) and external (e.g., task and environmental demands) factors. Although intriguing, causal evidence for this hypothesis remains scarce. Here, we investigated the causal effect of two neuromodulatory systems on behavioral and neural measures of perceptual and metacognitive decision-making. Specifically, we pharmacologically elevated levels of catecholamines (with atomoxetine) and acetylcholine (with donepezil) in healthy adult human participants performing a visual discrimination task in which we gauged decision confidence, while electroencephalography was measured. Where cholinergic effects were not robust, catecholaminergic enhancement improved perceptual sensitivity, while at the same time leaving metacognitive sensitivity unaffected. Neurally, catecholaminergic elevation did not affect sensory representations of task-relevant visual stimuli but instead enhanced well-known decision signals measured over the centroparietal cortex, reflecting the accumulation of sensory evidence over time. Crucially, catecholaminergic enhancement concurrently impoverished neural markers measured over the frontal cortex linked to the formation of metacognitive evaluations. Enhanced catecholaminergic neuromodulation thus improves perceptual but not metacognitive decision-making.


Asunto(s)
Clorhidrato de Atomoxetina , Catecolaminas , Toma de Decisiones , Electroencefalografía , Metacognición , Humanos , Masculino , Femenino , Toma de Decisiones/fisiología , Toma de Decisiones/efectos de los fármacos , Metacognición/fisiología , Adulto , Adulto Joven , Catecolaminas/metabolismo , Clorhidrato de Atomoxetina/farmacología , Percepción Visual/fisiología , Percepción Visual/efectos de los fármacos , Inhibidores de Captación Adrenérgica/farmacología , Acetilcolina/metabolismo
13.
Artículo en Inglés | MEDLINE | ID: mdl-39053579

RESUMEN

BACKGROUND: Posttraumatic stress disorder (PTSD) is characterized not only by its direct association with traumatic events but also by a potential deficit in inhibitory control across emotional, cognitive, and sensorimotor domains. Recent research has shown that a continuous sensorimotor feedback control task, the rapid assessment of motor processing (RAMP) paradigm, can yield reliable measures of individual sensorimotor control performance. This study used this paradigm to investigate control deficits in PTSD relative to both healthy volunteer and a non-PTSD psychiatric comparison group. METHODS: We examined control processing using the RAMP paradigm in a sample of 40 individuals with PTSD, along with matched groups of 40 individuals with mood and anxiety (MA) complaints and 40 healthy controls (HC). We estimated Kp (drive) and Kd (damping) parameters using a proportion-derivative (PD) control modeling approach. RESULTS: The Kp parameter was lower in the PTSD group compared to the HC (Cohen's d = .86) and MA groups (Cohen's d = 0.63). After controlling for color-word inhibition, Kp remained lower in the PTSD group versus HC (Cohen's d = 0.79) and versus MA (Cohen's d = 0.62). Mediation analysis showed that Kd significantly mediated the relationship between PTSD and control deficits in the Kp parameter, with 96% of the effect mediated by Kd. CONCLUSIONS: These findings underscore the potential of using dynamic control paradigms to elucidate the control dysfunctions in PTSD and suggests that different psychiatric conditions may distinctly influence subcomponents of sensorimotor control.

14.
Biol Psychol ; : 108850, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39074541

RESUMEN

Prior research suggests that cognitive control, indicated by NoGo N2 amplitudes in Go/NoGo tasks, is associated with dispositional anxiety. This negative association tends to be reduced in anxiety-enhancing experimental conditions. However, anxiety-reducing conditions have not yet been investigated systematically. Thus, the present study compares the effect of a relaxation instruction with the conventional speed/accuracy instruction in a Go/NoGo task on the correlation of the NoGo N2 with two subconstructs of dispositional anxiety, namely anxious apprehension and anxious arousal. As the test of differences between correlations needs considerable statistical power, the present study was included into the multi-lab CoScience Project. The hypotheses, manipulation checks, and the main path of pre-processing and statistical analysis were preregistered. Complete data sets of 777 participants were available for data analysis. Preregistered general linear models revealed that the different instructions of the task (speed/accuracy vs. relaxation) had no effect on the association between dispositional anxiety and the NoGo N2 amplitude in general. This result was supported by Cooperative-Forking-Path analysis. In contrast, a preregistered latent growth model with categorical variables revealed that anxious arousal was a negative predictor of the NoGo N2 intercept and a positive predictor of the NoGo N2 slope. Non-preregistered growth models, allowing for correlations of anxious apprehension with anxious arousal, revealed that higher anxious apprehension scores were associated with more negative NoGo N2 amplitudes with increased relaxation. Results are discussed in the context of the compensatory error monitoring hypothesis and the revised Reinforcement Sensitivity Theory.

15.
Curr Opin Behav Sci ; 592024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39070697

RESUMEN

Brain and behavior undergo measurable changes in their underlying state and neuromodulators are thought to contribute to these fluctuations. Why do we undergo such changes, and what function could the underlying neuromodulatory systems perform? Here we examine theoretical answers to these questions with respect to the locus coeruleus/norepinephrine system focusing on peripheral markers for arousal, such as pupil diameter, that are thought to provide a window into brain wide noradrenergic signaling. We explore a computational role for arousal systems in facilitating internal state transitions that facilitate credit assignment and promote accurate perceptions in non-stationary environments. We summarize recent work that supports this idea and highlight open questions as well as alternative views of how arousal affects cognition.

16.
J Sex Med ; 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39079074

RESUMEN

BACKGROUND: There are currently no Food and Drug Administration-approved treatments for female sexual arousal disorder (FSAD), which is physiologically analogous to male erectile dysfunction. AIMS: The study sought to test the systemic and local genital safety of topical sildenafil cream, 3.6% (sildenafil cream) among healthy premenopausal women with FSAD and their sexual partners over a 12-week treatment period. METHODS: This was a phase 2b, exploratory, randomized, placebo-controlled, double-blind study of sildenafil cream among healthy premenopausal women with FSAD. Safety was assessed by the frequency and incidence of treatment-emergent adverse events (TEAEs) among participants and their sexual partners. Participants recorded the incidence of TEAEs in a daily eDiary (electronic diary). Sexual partners were contacted within 72 hours of each sexual event in which investigational product was used. All participants used placebo cream for 1 month, during a single-blind run-in period, and then if eligible, were randomized 1:1 to sildenafil cream or placebo cream. Participants used their assigned investigational product over a 12-week double-blind dosing period. They attended monthly follow-up visits, in which their eDiary TEAE data were reviewed by the study staff and graded for severity and relationship to study product. OUTCOMES: The frequency and incidence of TEAEs among participants and their sexual partners. RESULTS: During the 12-week double-blind dosing period, there were 78 TEAEs reported by 29 of 99 sildenafil-assigned participants and 65 TEAEs reported by 28 of 94 placebo-assigned participants (P = .76). All TEAEs were mild or moderate in severity. The most common treatment-related TEAE among active and placebo-assigned participants was application site discomfort. There were no differences in the number of treatment-related TEAEs among sildenafil cream vs placebo cream users (P > .99). Four sildenafil cream participants and 3 placebo cream participants discontinued the study due to TEAEs involving application site discomfort (P > .99). There were 9 TEAEs reported by 7 of 91 sexual partners exposed to sildenafil cream vs 4 TEAEs reported by 4 of 84 sexual partners exposed to placebo cream (P = .54). CLINICAL IMPLICATIONS: These data support further clinical development of topical sildenafil cream for the treatment of FSAD. STRENGTHS AND LIMITATIONS: Safety was assessed among participants and their sexual partners after 1357 and 1160 sexual experiences in which sildenafil cream or placebo cream were used, respectively. The phase 2b study was powered for the primary objectives of efficacy, rather than safety. CONCLUSION: These data demonstrate that topically applied sildenafil cream was safe and well tolerated by exposed users and their sexual partners.

17.
J Sex Med ; 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39059373

RESUMEN

BACKGROUND: Efficacy assessments in clinical trials of treatments for female sexual arousal disorder (FSAD) and other female sexual dysfunction (FSD) diagnoses rely on various patient-reported outcomes (PROs). AIMS: We sought to compare 1-month recall PRO measures among participants enrolled in a clinical trial who provided these data without (test population) vs with (control population) use of an at-home, 24-hour recall electronic diary (eDiary), capturing similar data. METHODS: Preplanned subset analysis as performed during a phase 2b, exploratory, randomized, placebo-controlled, double-blind study of sildenafil cream, 3.6% (sildenafil cream) among healthy premenopausal women with FSAD. Preliminary product efficacy was assessed via 1-month recall and 24-hour recall questionnaires. A subset of the participants, the Evaluation of Recall Subset [ERS] provided PROs via the 1-month recall instruments but did not provide data via the 24-hour recall eDiary. OUTCOMES: Responses to the 1-month recall instruments were compared among ERS (test) vs non-ERS (control) participants. Among the non-ERS population, correlations between 1-month and 24-hour recall endpoints were calculated. RESULTS: There were no significant differences in the study co-primary 1-month recall efficacy endpoints, the Arousal Sensation (AS) domain of the 28-item Sexual Function Questionnaire (SFQ28) and the Female Sexual Distress Scale - Desire, Arousal, Orgasm question 14, among ERS vs non-ERS participants during the initial 1-month no-drug run-in period or the 1-month single-blind placebo run-in period (P values > .47). Scores on these 1-month recall PROs continued to be similar after randomization for sildenafil cream (P values > .30) and placebo cream (P values > .20) assigned ERS and non-ERS participants during the 3-month double-blind dosing period. There were strong correlations between the SFQ28 AS and eDiary AS scores during the no-drug run-in (R = 0.79, P < .01) and the single-blind run-in (R = 0.73 P < .001). During the double-blind dosing period, the SFQ28 AS score continued to be highly correlated with the eDiary AS score among sildenafil cream users (R = 0.83; P < .001) and placebo cream users (R = 0.8; 2 P < .001). CLINICAL IMPLICATIONS: There was no evidence that 1-month recall PRO instruments introduce recall bias; assessing arousal sensations with 24-hour vs 1-month PRO instruments is similar and either method could be used to assess efficacy depending on study objectives. STRENGTHS AND LIMITATIONS: This preplanned subset analysis compared efficacy of PROs based on recall duration. While the subset was preplanned, the study was powered to detect significant differences in the primary efficacy objectives, not among this subset analyses. CONCLUSION: These data will be used in planning future efficacy assessments of sildenafil cream for FSAD. CLINICAL TRIAL REGISTRATION: This clinical trial was registered with ClinicalTrials.gov, NCT04948151.

18.
Biol Open ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38989667

RESUMEN

This research provides an in-depth exploration into the triggers and corresponding autonomic responses of piloerection, a phenomenon prevalent across various species. In non-human species, piloerection occurs in reaction to a variety of environmental changes, including social interactions and temperature shifts. However, its understanding in humans has been confined to emotional contexts. This is problematic because it reflects solely upon subjective experience rather than an objective response to the environment. Further, given our shared evolutionary paths, piloerection should function similarly in humans and other animals. I observed 1,198 piloerection episodes from eight participants while simultaneously recording multiple autonomic and body temperature indices, finding that piloerection in humans can be elicited by thermal, tactile, and audio-visual stimuli with equal effectiveness. The data also revealed variations in cardiac reactivity measures: audio-visual piloerection was associated with greater sympathetic arousal, while tactile piloerection was linked to greater parasympathetic arousal. Despite prevailing notions of piloerection as a vestigial response in humans, it does respond to decreases in skin temperature and is associated with a rise in skin temperature during episodes. This research underscores that piloerection in humans is not purely vestigial, nor is it solely an affective response to emotional stimuli. Rather, it is best understood as a reflexive response to environmental changes, suggesting a shared functional similarity with other species.

19.
Brain Circ ; 10(2): 119-133, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39036297

RESUMEN

BACKGROUND: Disorders of consciousness (DOC) incorporate stages of awareness and arousal. Through coma arousal therapy sensory deprivation experienced by patients with DOC can be mitigated. Nevertheless, consensus concerning its effectiveness on these patients is still fractional. PURPOSE: This review aims to investigate the effectiveness of coma arousal therapies on patients with DOC. METHODS: A meta-analysis was performed by searching electronic databases using search terms, the studies investigating the effect of coma arousal therapy in patients with DOC using the Coma Recovery Scale-Revised and Glasgow Coma Scale as outcome measures were included. The risk of bias was assessed, using Cochrane and Joanna Briggs Institute critical appraisal tools. Further, analysis was conducted for the included studies. RESULTS: Out of 260 studies, 45 trials were reviewed and assessed for bias, with 31 studies included for analysis. The analysis demonstrates a significant difference in pre- and post - sensory stimulation, vagus nerve stimulation, transcranial magnetic stimulation, and transcranial direct current stimulation. Sensory stimulation showed the greatest mean difference of -4.96; 95% CI = -5.76 to - 4.15. The patients who underwent intervention after 3 months of illness showed significant improvement. CONCLUSION: The result shows that sensory stimulation, transcranial magnetic stimulation, and transcranial direct stimulation can improve behavioral outcomes of patients with DOC, wherein sensory stimulation is found to be more effective.

20.
Sleep Adv ; 5(1): zpae039, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39036744

RESUMEN

Background: Opioids are effective for acute pain management following surgery among adolescents, yet are associated with significant negative consequences, including respiratory depression and opioid misuse. Sleep deficiency is common following surgery and extant research indicates strong cross-sectional associations between sleep deficiency and increased problematic opioid use. Objective: This study examined longitudinal associations between postsurgical sleep deficiency and opioid use among adolescents undergoing outpatient surgery. We also examined daily pain and mood as mechanisms linking previous night's sleep deficiency and next day prescription opioid use. Methods: This prospective, observational study enrolled 106 adolescents (11-19 years) who underwent orthopedic outpatient surgery and collected pre-surgery and longitudinal measurements. Participants were 52% female, African-American (7%), American Indian/Alaska Native (7%), Hispanic (9%), Native Hawaiian or Other Pacific Islander (4%), or white, non-Hispanic (66%). Using ecological momentary assessment methods, participants reported sleep, pain, and mood in real time over the first 14 days following surgery. Postsurgical opioid use was measured using an electronic medication cap monitoring device, eCAPTM. Associations between variables were measured using multilevel structural equation modeling. Results: Using multi-level mediation models, pain, but not mood-mediated associations between postsurgical sleep deficiency (sleep quality, total sleep time, sleep onset latency, and wake after sleep onset) and opioid use, at both the within-person and between-person levels. Results highlight that greater previous night's sleep deficiency (both generally and greater than a person's mean level) was associated with higher next day pain (both generally and greater than a person's mean level), which, in turn, was associated with higher opioid use. Furthermore, between-person total effect models provide support for sleep deficiency predicting higher opioid use. Conclusions: Our findings should be considered preliminary yet underscore the need for a comprehensive and personalized approach to postsurgical pain management and opioid use, potentially implementing interventions targeting sleep quality and quantity to reduce pain and opioid use.

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