BackgroundParoxysmal sympathetic hyperactivity (PSH) is a devastating complication of traumatic brain injury (TBI), characterized by the simultaneous onset of various manifestations due to sympathetic overactivity. Paradoxical bradycardia, an uncommon manifestation of PSH, is poorly characterized, and there is limited evidence regarding its clinical features, pathophysiological mechanisms and targeted management.Case presentationA 25-years-old male sustained severe traumatic brain injury in a nighttime motorcycle collision with a parked vehicle and underwent multiple neurosurgical procedures. He developed typical PSH on day 48 post injury, with a Paroxysmal Sympathetic Hyperactivity Assessment Measure (PSH-AM) score of 27. On the 92nd day post-injury, the patient developed persistent resting bradycardia (40–66 beats/min) after cranioplasty, while a reduced maximum heart rate (140–159 beats/min) was noted during PSH episodes. He subsequently experienced an acute PSH episode with severe bradycardia (38–43 beats/min, PSH-AM score of 20). After excluding common predisposing factors, intravenous isoproterenol (initial dose 4 μg/min, titrated to 2 μg/min) was administered in combination with anti-PSH medication regimen, and the patient’s clinical symptoms were relieved. The patient was discharged in a stable condition and had no further episodes of bradycardia at the 3-months follow-up.ConclusionParadoxical bradycardia represents an atypical clinical phenotype of post-TBI PSH, likely mediated by an atypical Cushing reflex secondary to fluctuating intracranial pressure elevations during PSH exacerbations. Clinically, for TBI patients with unexplained bradycardia, potential primary causes should be actively explored, with particular attention to monitoring dynamic changes in intracranial pressure.
Bridging the gap from mechanism to clinic: a translational perspective on taVNS for gastrointestinal disorders
In recent years, multiple clinical and translational studies have investigated the application and mechanisms of transcutaneous auricular vagus nerve stimulation (taVNS) in gastrointestinal disorders (GIDs), with consideration given to pathophysiology, stimulation parameters, and patient-specific factors. In this review, we systematically synthesize recent evidence from clinical trials and preclinical models published in leading gastroenterology and neurology journals. Our focus is on taVNS-mediated modulation of the brain–gut axis, particularly its role in improving autonomic balance, reducing visceral sensitivity, and attenuating inflammatory responses, with the aim of enhancing therapeutic outcomes in functional and inflammatory GIDs. There is a need to optimize stimulation protocols through mechanistic insights and to promote the use of this non-invasive, well-tolerated neuromodulation approach. These advances are essential for expanding taVNS accessibility in clinical practice, especially for patients with refractory symptoms, comorbid psychological conditions, and in settings where conventional treatments are limited or contraindicated. Personalized taVNS strategies and biomarker-guided dosing represent emerging trends in neuromodulation therapy. However, standardized protocols and predictive models have yet to be established for widespread clinical implementation.
Body mass index affects EEG microstate dynamics through blood viscosity in high-altitude environments
High-altitude hypoxia imposes substantial challenges on cerebral oxygen delivery and brain functional regulation. Body mass index (BMI) may influence neurophysiological adaptation to such environments through metabolic and hemorheological pathways, yet its relationship with resting-state Electroencephalography (EEG) microstate dynamics remains unclear. This study examined whether blood viscosity (BV) mediates the association between BMI and EEG microstate characteristics in a high-altitude population. A total of 123 permanent residents from Lhasa, Tibet, were initially included. Because only five participants met the obesity criterion, the main statistical analyses were conducted in 118 participants after excluding the obese subgroup. Resting-state eyes-closed EEG data were recorded using a 64-channel system, and standardized 180-s artifact-free segments were used for microstate analysis. Four canonical microstates were identified, and temporal parameters, including coverage, duration, global explained variance, global field power, occurrence, and transition probabilities, were extracted. BMI was calculated from measured height and weight, and BV was estimated using hematological indicators based on a validated high-altitude prediction model. The four identified microstate maps showed topographic patterns broadly consistent with previous EEG microstate studies. Microstate C showed the highest values across several temporal parameters, suggesting a potentially dominant resting-state pattern under high-altitude conditions. BMI was positively correlated with BV, while BV was negatively correlated with the occurrence of microstate B. The mediation model suggested an indirect statistical pathway from BMI to microstate B occurrence through estimated BV: higher BMI was associated with higher estimated BV, which in turn was associated with reduced microstate B occurrence. These findings suggest that BMI-related alterations in resting-state brain dynamics at high altitude may be linked to hemorheological changes. Overall, this study provides preliminary evidence for a BMI–blood viscosity–brain microstate pathway in high-altitude residents. The results highlight BV as a potential physiological bridge between body composition and spontaneous brain activity under chronic hypoxic exposure.
Acoustic stimulation in pain management: neurobiological mechanisms and clinical applications—a narrative review
Pain affects over 30% of the global population, with an underlying pathogenesis involving a complex interplay of biopsychosocial factors. Despite the availability of conventional pharmacological and interventional therapies, their clinical utility is frequently constrained by concerns regarding substance misuse, surgical complications, and other adverse sequelae. Acoustic stimulation (AS) has emerged as a promising alternative in pain management, characterized by its non-invasive nature, favorable safety profile, and high cost-effectiveness. However, current literature lacks a comprehensive evaluation of cutting-edge AS technologies and a profound decryption of its pleiotropic analgesic mechanisms, which has hindered the integration of AS into multimodal analgesic strategies. This review provides the first comprehensive synthesis of the neurobiological mechanisms and clinical applications of AS. We comprehensively evaluate the analgesic efficacy of diverse modalities, ranging from established interventions—such as music therapy (MT), natural sounds (NS)/noise, and auditory beat stimulation (ABS)—to emerging approaches, including vibroacoustic therapy (VAT) and immersive interactive technologies that integrate multisensory acoustic information. Emerging evidence suggests that AS exerts its therapeutic effects via a multidimensional neurobiological framework, notably through the modulation of corticothalamic circuits, the activation of descending pain-inhibitory systems, and the dynamic regulation of neurochemical mediators. Clinical data consistently highlight the adjunctive value of MT, NS/noise, and VAT in the management of both acute and chronic pain. Furthermore, the convergence of AS with immersive interactive technologies is pioneering a novel digital intervention paradigm, facilitating the seamless integration of AS into multimodal analgesic frameworks. Collectively, these findings suggest that AS represents a robust, non-pharmacological strategy that warrants further exploration as a cornerstone of future personalized, multimodal pain management.
Enhancing adult neurogenesis attenuates hippocampal-related behavioral deficits in an Alzheimer’s mouse model
Alzheimer’s disease (AD) is the most prevalent form of dementia, characterized by progressive memory loss, cognitive decline, and emotional dysregulation. Adult hippocampal neurogenesis (AHN) critically contributes to cognition and mood but undergoes precipitous decline during AD progression. Here, we investigated whether enhancing AHN through genetic expansion of endogenous neural stem cells (NSC) ameliorates AD-related phenotypes. Using lentiviral overexpression of the cell cycle regulators Cdk4 and CyclinD1 in the dentate gyrus of 3xTg-AD mice, we show that enhancing AHN is accompanied by partial improvements in selected behavioral measures associated with hippocampal function, including in the open-field test and Morris water maze. These findings indicate that the AD-compromised neurogenic niche remains responsive to NSC-targeted stimulation and support the use of AHN as a potential additional avenue for multi-modal therapeutic strategies for AD.
Network analysis of spousal support and fear of childbirth in pregnant women of advanced maternal age
BackgroundFear of childbirth is an important perinatal mental health concern, particularly among women of advanced maternal age. However, the specific interrelations between spousal support and fear of childbirth remain unclear.MethodsThis cross-sectional study recruited 279 pregnant women of advanced maternal age from a tertiary hospital in Henan, China, using convenience sampling. Spousal support and fear of childbirth were assessed using the Spouse Support Inventory and the Childbirth Attitude Questionnaire. A regularized partial-correlation network was estimated using EBICglasso, and central and bridge nodes were identified. Network stability was examined using bootstrap procedures.ResultsThe prevalence of any fear of childbirth, defined as a CAQ score ≥28 and including mild, moderate, and severe categories, was 86.4% (n = 241). Negative associations predominated between the spousal support and fear of childbirth communities. The strongest cross-community association was observed between “teaching you how to do things you do not know how to do” and “concern about fetal health.” The most central nodes were “participating in activities together to reduce your stress” and “providing you with helpful information,” whereas the strongest bridge nodes were “helping you understand why things did not go well” and “giving you encouragement.ConclusionSpecific supportive behaviors, especially informational and cognitive-appraisal support, occupied central positions in the network linking spousal support and fear of childbirth among pregnant women of advanced maternal age. Strengthening these forms of spousal support may inform the development of couple-based interventions to reduce childbirth fear and promote perinatal mental health.
Psychotherapy initiation is associated with discontinuation of psychotropic medications without dose escalation: a ten-year real-world cohort study (2014-2024)
BackgroundIncreasing psychotropic prescribing has raised concerns about long-term safety and regimen complexity in mental health care. Although psychotherapy is an established treatment, its role in medication optimization and psychotropic medication reduction in real-world practice across patient subgroups remains insufficiently characterized.ObjectiveTo evaluate whether initiation of psychotherapy is associated with short-term changes in psychotropic medication exposure and regimen complexity, and to examine differences by sex, age, and diagnostic category. Methods: A retrospective cohort study was conducted using anonymized pharmacy dispensing data from the Mental Health Service of Hospital Marina Baixa (Alicante, Spain) between 2014 and 2024. Patients with at least one active prescription for a benzodiazepine or antidepressant within 90 days before psychotherapy initiation were included. Psychotropic exposure was compared in symmetric 90-day pre- and post-therapy windows using number of active agents, total Defined Daily Doses, and prevalence of benzodiazepine and antidepressant use, with stratified analyses by sex, age group, and diagnosis.ResultsThe cohort comprised 86,502 patients and 20.76 million dispensations. The median number of psychotropic medications decreased from 5 to 2 (p < 0.001), while total dose remained stable (median Defined Daily Dose ≈ 21.7; p = 0.999). Benzodiazepine use declined from 87.6% to 67.5% and antidepressant use from 81.8% to 68.8% (both p < 0.001). Men were more likely than women to discontinue benzodiazepines (odds ratio 1.27, 95% confidence interval 1.13–1.43), and simplification increased with age (median reduction −1 in <18 years to −4 in ≥65 years). The largest benzodiazepine reductions occurred in depressive, personality, and episodic mood disorders (−23 to −27 percentage points).ConclusionsIn routine public mental health care, psychotherapy initiation is associated with substantial simplification of psychotropic treatment regimens without increasing overall medication dose, supporting a potential role in facilitating rational medication simplification.
Editorial: Psychological health in the digital age across global communities
Cognitive-attitudinal factors predict CBT-I enrollment willingness in Chinese sleep clinic patients: a knowledge-attitudes-practices survey
BackgroundDespite strong evidence for cognitive behavioral therapy for insomnia (CBT-I), uptake remains constrained by poorly understood cognitive, attitudinal, and practical barriers. This study examined determinants of willingness to enroll in sleep improvement programs among adults at risk of sleep disorders—including insomnia, obstructive sleep apnea, and comorbid psychological distress—attending a tertiary sleep clinic in China.MethodsA cross-sectional knowledge-attitudes-practices survey was conducted among 2,661 adults attending the sleep and behavioral medicine outpatient clinic at Ganzhou Hospital-Nanfang Hospital, Southern Medical University, Ganzhou, Jiangxi, China, between February 2022 and June 2025. Willingness to enroll in a structured sleep improvement program was assessed alongside sleep health knowledge, perceived need, CBT-I versus medication effectiveness beliefs, telehealth acceptability, clinical severity (Insomnia Severity Index, Epworth Sleepiness Scale, STOP-Bang), psychological symptoms (PHQ-2, GAD-2), perceived barriers, and sociodemographic characteristics. Multivariable logistic regression identified independent predictors of willingness to enrollment, with secondary analyses evaluating model discrimination and testing prespecified interactions.ResultsAmong 2,661 participants (median age 45 years, 56.5% female, median ISI = 13), 1,386 (52.1%) expressed willingness to enroll. Univariable comparisons showed no significant differences between willing and not-willing groups across demographics, clinical characteristics, or barriers (all p>0.05). However, multivariable modeling revealed that when considered simultaneously, cognitive-attitudinal factors emerged as significant independent predictors, suggesting complex interactions rather than simple bivariate associations. In multivariable models, perceived need (OR = 1.20, 95% CI: 1.16–1.25, p<0.001), beliefs that CBT-I is more effective and durable than sleep medication (OR = 1.12, 95% CI: 1.08–1.16, p<0.001), sleep health and treatment knowledge (assessed by a six-item knowledge score) (OR = 1.09, 95% CI: 1.05–1.13, p<0.001), and anxiety symptoms (OR = 1.07, p=0.005) positively predicted willingness. Paradoxically, depression symptoms (OR = 0.94, p<0.001) and insomnia severity (OR = 0.93, p<0.001) inversely predicted willingness. Model discrimination was modest (AUC = 0.543, 95% CI: 0.504–0.590). Time (mean 3.54) and cost (3.44) were most severe barriers but showed no independent association with willingness (p>0.05).ConclusionCognitive-attitudinal factors (perceived need, CBT-I beliefs, knowledge) independently predicted enrollment willingness, whereas demographics and practical barriers did not. Depression and insomnia severity paradoxically reduced willingness, creating an inverse care law. However, poor model discrimination and measurement of stated willingness rather than actual enrollment limit conclusions. Prospective validation and motivational enhancement strategies for patients with depression are needed.