ABSTRACT Irritable bowel syndrome (IBS) is a chronic disorder of gut–brain interaction causing significant psychosocial burden. Increasing evidence suggests that autonomic nervous system dysfunction, maladaptive stress responsivity, and abnormal central pain processing play central roles in IBS pathophysiology. Altered sympathovagal balance, reduced parasympathetic tone, and dysregulated hypothalamic‐pituitary‐adrenal (HPA) axis activity have been consistently associated with symptom severity and quality of life. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulatory intervention that modulates cortical excitability, autonomic regulation, emotional processing, and pain perception through targeted electromagnetic stimulation. Various brain areas and networks have shown altered activity and functional connectivity in IBS. Targeting these areas has been reported to be effective in the alleviation of IBS symptoms. Among these areas, stimulation of the dorsolateral prefrontal cortex (DLPFC) could modulate autonomic function. This review summarizes current evidence regarding autonomic abnormalities and stress dysregulation in IBS and evaluates the potential role of rTMS in modulating these mechanisms. Particular emphasis is placed on heart rate variability, visceral pain pathways, HPA‐axis dysfunction, emotional regulation, and cortical‐limbic‐autonomic interactions. Existing evidence suggests that rTMS may represent a promising neuromodulatory strategy for IBS; however, large‐scale studies remain necessary to establish optimal stimulation targets and protocols and long‐term efficacy.
ABSTRACT Glaucoma is conventionally characterized as an intraocular pressure‐dependent optic neuropathy; however, emerging evidence features glaucoma as a complex neurodegenerative disorder of the central nervous system, closely linked to systemic physiological dysregulation. This review aims to combine a rapidly expanding frontier in vision research: the integration of neurotrophic signaling, sleep architecture, and retinal neuroprotection. Neurotrophic factors, particularly the brain‐derived neurotrophic factor‐TrkB axis, are indispensable for the survival and synaptic integrity of retinal ganglion cells. In glaucoma, mechanical and metabolic stressors disrupt the retrograde axonal transport of these survival signals. Furthermore, recent paradigms reveal that neurotrophin expression and downstream signaling cascades are highly modulated by sleep‐wake cycles and circadian rhythms. Sleep fragmentation and chronic sleep disorders, such as obstructive sleep apnea, not only suppress central and ocular neurotrophin synthesis but also exacerbate neuroinflammation, trigger microglial activation, and induce nocturnal ocular perfusion pressure fluctuations. Moreover, the newly characterized ocular glymphatic system shows a highly sleep‐dependent waste clearance mechanism, where sleep deprivation compromises the elimination of neurotoxic aggregates from the optic nerve head. Rather than summarizing this previously separate literature in parallel, this review synthesizes them into a single causal context, explicitly graded by the level of evidentiary certainty, and extends this basis to the clinical dimension of retinal ganglion cell‐related mood disturbance. By integrating these distinct fields, this review proposes an interconnected pathophysiological loop where sleep disturbances diminish neurotrophic support and impair metabolic clearance, rendering retinal ganglion cells highly vulnerable to glaucomatous degeneration. Finally, this review will discuss the therapeutic implications of this network, highlighting chronotherapeutic optimization of intraocular pressure‐lowering agents, small‐molecule TrkB agonists, and targeted sleep interventions as novel, adjuvant neuroprotective strategies. Ultimately, bridging sleep science and sensory neuroscience offers a promising, holistic framework for preserving vision in glaucoma patients.
Age‐related hearing loss (ARHL) is a degenerative disorder of the auditory system, characterized by bilateral symmetrical sensorineural hearing loss that occurs with aging. As a highly prevalent age‐related condition worldwide, ARHL significantly impairs both the quality of life and mental health of the elderly. The pathogenesis of ARHL involves multifactorial mechanisms, with primary pathological features including elevated hearing thresholds, loss of hair cells, degeneration of spiral ganglion neurons, and damage to the stria vascularis. In this review, we summarize the pathogenesis of ARHL, which includes oxidative stress, DNA damage, and inflammation, ultimately contributing to the activation of cell death pathways such as apoptosis, ferroptosis, and pyroptosis. Building upon this mechanistic understanding, preventive strategies focus on minimizing exposure to environmental risk factors such as chronic noise, tobacco, and alcohol consumption. Current therapeutic approaches primarily involve pharmacological interventions targeting oxidative stress, hormonal therapies, and emerging gene‐editing technologies. Notably, regenerative medicine strategies that utilize stem cell‐based technologies to reconstruct cochlear hair cells represent a promising therapeutic direction for future research. In conclusion, a deeper understanding of the multifaceted mechanisms underlying ARHL holds significant promise for developing targeted preventive and therapeutic strategies to improve auditory health and quality of life of the elderly.
To explore associations of vestibular disorders with all‐cause and cause‐specific dementia and underlying biological mechanisms/neuroimaging changes. A population‐based cohort study of 406,348 UK Biobank participants was conducted. Inverse probability of treatment weighting (IPTW) balanced baseline covariates, and Cox proportional hazards models estimated hazard ratios (HRs) for dementia outcomes. Inflammatory markers, plasma metabolites, and brain structure changes were analyzed. During 13.9 (SD 2.1) years of follow‐up, 6702 dementia cases occurred. Vestibular disorders were linked to higher risks of all‐cause dementia (HR 1.86 and 95% CI 1.04–3.30), Alzheimer's disease (AD, 2.36, and 1.01–5.51), and vascular dementia (VD, 3.35, and 1.48–7.59). Eight metabolites (e.g., VLDL cholesterol, and histidine) mediated the vestibular disorder‐dementia association. Vestibular disorders also correlated with alterations in dementia‐related brain structures (cortex, subcortical regions, and white matter tracts). Vestibular disorders increase all‐cause and cause‐specific dementia risk. This modifiable factor should be incorporated into dementia prevention initiatives.
Meniere disease (MD) is an inner ear disorder characterized by episodic vertigo, tinnitus, fluctuating sensorineural hearing loss (SNHL), and aural fullness. Its hallmark pathological feature is endolymphatic hydrops. MD shows significant familial clustering in European and East Asian populations, supporting a strong genetic component in disease susceptibility. Dysfunctional sensory epithelia, particularly in the cochlea and vestibular organs, are increasingly recognized as central to the development of SNHL in MD patients. Notably, numerous non‐syndromic hearing loss genes such as OTOG, MYO7A, TECTA, or TRIOBP are expressed in sensory epithelial cells across the inner ear, including hair cells and supporting cells. Rare variants in these MD‐associated genes may contribute to MD pathogenesis through disruption of hair cell stereocilia, interfering mechanoelectrical transduction, disturbing ionic homeostasis, or affecting inner ear development. This review aims to summarize the current evidence on SNHL genes expressed in the inner ear sensory epithelium and their potential role in the molecular pathophysiology of MD.
Chronic pain is increasingly conceptualized as a network‐level neuroplasticity disorder involving maladaptive interactions among sensory, affective‐salience, and descending modulatory pathways. This narrative review synthesizes evidence for non‐invasive brain stimulation (NIBS) in chronic pain—transcranial magnetic stimulation (TMS), transcranial electrical stimulation (tES), and low‐intensity transcranial focused ultrasound (LITUS)—and outlines systems neuroscience‐grounded routes to personalization. High‐frequency motor cortex rTMS shows the most consistent, though modest, short‐term analgesic effects, especially in neuropathic pain and fibromyalgia, and currently has the strongest guideline support. tES, particularly tDCS, produces small, heterogeneous benefits with low‐certainty evidence, whereas tACS and tRNS remain largely experimental. LITUS provides millimeter‐scale focality and access to deep pain‐relevant structures, with early preclinical and human studies suggesting promising but preliminary analgesic effects. Across modalities, responses are highly variable and usually short‐lived, reflecting reliance on population‐derived targets and protocol‐based dosing that disregard individual network organization. We highlight emerging strategies for target and parameter personalization, including graph‐theoretical targeting, individualized electric/acoustic field modeling, and closed‐loop neuromodulation guided by electrophysiological and imaging biomarkers, to enable more mechanism‐ and network‐informed, phenotype‐sensitive NIBS for chronic pain.
Kanamycin (KM), a widely used aminoglycoside antibiotic, is limited by its ototoxic side effects, primarily targeting cochlear outer hair cells (OHCs) and leading to irreversible sensorineural hearing loss. Our previous work showed that silencing AMP-activated protein kinase alpha 1 (AMPKα1) prevents noise-induced hearing loss through a redox-sensitive regulatory mechanism. Given that both noise-induced and aminoglycoside-induced hearing loss share oxidative stress as a key pathological feature, we tested whether AMPKα1 silencing could mitigate KM-induced damage using an acute ototoxic model combining KM with furosemide (KM + FU). KM + FU exposure markedly increased AMPKα phosphorylation at Thr172. Targeted siRNA-mediated silencing via posterior semicircular canal delivery in CBA/J mice significantly reduced AMPKα1 expression in OHCs and effectively prevented KM + FU-induced OHC loss and hearing impairment. This preventive effect was independent of stria vascularis permeability or cochlear KM uptake. These findings identify AMPKα as a contributor to KM + FU-induced acute ototoxicity and suggest that its inhibition may be a promising strategy for hearing preservation.
ABSTRACT Hearing loss is a leading modifiable risk factor for dementia, yet evidence that hearing interventions reduce dementia risk has been mixed and difficult to translate into practice. Jiang and colleagues address this gap by shifting the focus from hearing aid uptake to hearing aid effectiveness in a pooled analysis of 61,089 adults with hearing loss aged 55+ across seven longitudinal cohorts from 33 countries. Hearing aid use was associated with a modestly lower risk of probable dementia overall (Hazard Ratios, HR, 0.91), but the association was confined to participants reporting improvements in hearing (HR 0.86), with no apparent benefit among those reporting poor improvement in hearing (HR 0.98). Associations were stronger in middle‐income settings (HR 0.76) and in several demographic subgroups, underscoring the potential equity and implementation implications. We argue these findings reposition quality hearing rehabilitation as the key exposure for dementia prevention in adults with hearing loss, and outline priorities to standardize effectiveness measurement, incorporate effectiveness‐oriented endpoints into trials and routine hearing care, and develop implementation strategies that optimize real‐world benefit.
ABSTRACT Olfaction is not only a chemical sensing system but also a neural functional module highly coupled with emotions, memories, and value judgments. Due to the unique direct cortical projection structure of the olfactory pathway, its damage cannot be fully restored through drugs or peripheral repair, leading to the emergence of bioelectronic noses. In recent years, brain–machine interface (BMI) technology targeting the higher olfactory cortex has become an important direction for olfactory reconstruction and artificial olfaction generation. This technology activates regions such as the piriform cortex, amygdala, and orbitofrontal cortex through electrical, biochemical, or optical modulation methods, bypassing the damaged peripheral system to realize the reproduction or substitution of odor perception. The rapid development of technologies such as neural interface materials, wireless recording, optogenetics, closed‐loop stimulation, and deep learning decoding has made it possible for in vivo bioelectronic noses to move from proof‐of‐concept to functional systems. This review systematically summarizes the regulatory basis of olfactory circuits and higher brain regions, in vivo neural recording and stimulation technologies, signal processing and deep decoding methods, typical applications, while proposing future roadmap suggestions, which can promote the advancement of olfactory neural prostheses from basic research to clinical applications.
ABSTRACT Hearing loss is the most common disabling disease among humans, which adversely affects human health. Sensorineural hearing loss (SNHL) accounting for approximately 63% of all hearing loss cases. SNHL may be classified into age‐related hearing loss (ARHL), drug‐induced hearing loss (DIHL), noise‐induced hearing loss (NIHL), and sudden sensorineural hearing loss (SSHL). Up to now, there are some recognized theories of SNHL, mainly including oxidative stress theory, vascular damage theory, and metabolic damage theory. However, the mechanism of SNHL has not yet been fully elucidated due to the highly complex etiologies, pathogenic mechanisms, and pathogenic changes in various types of hearing loss. In addition, the clinical treatment of SNHL is also varied. It mainly includes drug therapy, gene therapy, cochlear implantation, and so on. However, in view of the complex pathogenesis of SNHL, it is still insufficient to find precise and individualized treatment strategies. In this review, we thoroughly elucidate the classification and various pathogenesis of SNHL and introduce various treatment strategies for SNHL in detail, in order to provide scientific evidence for understanding the pathological process of SNHL and rational application of SNHL treatment.
ABSTRACT Plantar and dorsal von Frey (VF) filament assays are widely used to assess mechanical nociception in rodents following peripheral nerve injury, spinal cord injury, and analgesic interventions. However, the effects of repeated testing on withdrawal thresholds and potential sensitization have not been well defined. In the current study, we performed various plantar and dorsal VF assays on unoperated male and female Lewis or Sprague‐Dawley rats with minimally or highly repetitive VF testing schedules across 1–15 days with various rest intervals between days. Plantar VF assays were performed at the tibial‐innervated midplantar region eight times per day at hourly intervals (Group #1). Dorsal VF filaments were applied to sural‐ and saphenous‐innervated regions under four different schedules: (Group #2) eight times at hourly intervals per day at bilateral sural regions; (Group #3) once per day at bilateral sural and saphenous regions; (Group #4) twice per day at bilateral sural and saphenous regions; and (Group #5) eight times per day at hourly intervals at the left sural region and twice per day at all other regions to detect non‐local effects. Minimally repetitive dorsal VF tests (Groups #3 and 4) did not produce sensitization. In contrast, highly repetitive plantar (Group #1) and dorsal VF tests (Groups #2 and #5) all produced significant local sensitization that intensified across consecutive days of testing. Group #5 also showed non‐local sensitization at minimally tested regions. Recovery from sensitization occurred after rest intervals following highly repetitive dorsal VF tests (Groups #2 and 5), but not plantar VF tests (Groups #1). Animal restlessness due to repeated handling and testing did not affect results. No significant sex (Groups #1, 2, and 5) or strain differences (Groups #2 and 5) were found within or across the groups for average VF withdrawal thresholds or sensitization. In summary, highly repetitive VF tests can produce sensitization and should be treated as a methodological variable.
The olfactory system plays a vital role in our lives. A large number of studies have shown that olfactory receptors are implicated in crucial metabolic pathways, such as the metastasis, invasion, and migration of cancer cells. They have also become potential therapeutic targets for various types of cancer, and some have even been the focus of clinical trials. Our review emphasizes the involvement of olfactory receptors in cancer cell metabolism and identifies specific olfactory receptors associated with particular types of cancer, providing new directions for research on cancer treatment.
Tinnitus is a prevalent auditory perceptual disorder, characterized by a subjective sensation of sound without any external acoustic signals. This disorder significantly impacts the quality of daily life of patients. The pathogenesis of tinnitus is complex and generally associated with auditory system damage and abnormal neural activity. Much evidence from individuals with tinnitus indicates that alterations in the rhythmic oscillatory activity of cortical neurons correlate with tinnitus perception. Here, we review the role of neural oscillations across various frequency bands in auditory processing and the pathogenesis of tinnitus. The thalamocortical dysrhythmia (TCD) model proposes that deafferentation leads to altered auditory thalamocortical oscillations, where resting-state alpha activity is replaced by theta–gamma cross-frequency coupling. Additionally, altered oscillatory neural network connectivity in patients with tinnitus suggests modified interactions between various brain regions including auditory and nonauditory areas. We also summarize neural oscillation-based therapeutic approaches, emphasizing precision medicine in tinnitus treatment. This review focuses on the relationship between neural oscillations and tinnitus and related pathogenesis. Targeting neural modulation within specific frequency bands may open up new avenues for tinnitus therapy in clinical practice.
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by both motor and non-motor symptoms, with dysphagia being one of the most frequent and debilitating complications in advanced stages. Deep brain stimulation (DBS), widely used to alleviate motor symptoms in PD, has recently drawn attention for its potential effects on swallowing mechanisms. This narrative review synthesizes the available evidence regarding the relationship between DBS and dysphagia in individuals with PD. The findings indicate that DBS may improve swallowing reflex initiation, coordination of the pharyngeal phase, and reduce aspiration risk; however, inconsistent outcomes have also been reported, including symptom worsening or no significant changes in swallowing function. The variability in results may be attributed to differences in stimulation parameters, target areas, assessment methods, and individual characteristics. Despite the promising therapeutic potential of DBS, current evidence remains inconclusive due to small sample sizes, methodological heterogeneity, and short follow-up durations. Future research should involve larger, well-designed studies with standardized assessment protocols to clarify the long-term efficacy of DBS for dysphagia in PD and to optimize individualized treatment strategies that may include combined rehabilitation approaches.
Sensory neuron disorders, such as peripheral neuropathies and trigeminal neuralgia, cause chronic pain and sensory dysfunction; however, regenerative treatments are limited. Human pluripotent stem cells (hPSCs) provide a powerful platform to model these diseases by generating functional sensory neuron subtypes, including nociceptors and mechanoreceptors. These hPSC-derived neurons mimic key features of dorsal root ganglia (DRG), enabling the study of disease mechanisms and therapeutic responses in a human-relevant system. When combined with functional genomics—such as CRISPR screens, single-cell RNA-seq, and epigenomic profiling—these models allow for the discovery of pathogenic pathways and drug targets. Patient-specific iPSC-derived neurons also support personalized medicine approaches. Brain organoids and animal models complement these systems by offering broader developmental insights and enabling in vivo validation. However, challenges remain in achieving full maturation, subtype specificity, and functional integration of hPSC-derived neurons. Ethical and safety considerations with gene editing also persist. Continued advances in differentiation protocols, multi-model integration, and collaborative efforts are key to unlocking the full therapeutic potential of stem cell-derived sensory neurons. This perspective highlights recent progress in disease modeling and treatment strategies using hPSC-derived neurons and functional genomics.
Music, as an auditory stimulus, has long been recognized for its ability to evoke heart rate variability (HRV) responses. In patients with disorders of consciousness (DOC), these responses may provide valuable insights into consciousness levels. However, the diagnostic value of music-induced HRV and the influence of music type remain unclear. This study evaluated HRV under baseline (BL), patient-preferred music (PPM), and therapist-selected music (TSM) conditions in 15 minimally conscious state (MCS) and 14 vegetative state (VS) patients. Six HRV metrics showed significant differences between MCS and VS groups exclusively during TSM. Principal component analysis reduced these metrics into two components (PC1 was predominantly weighted by HF kurtosis, reflecting vagal modulation, whereas PC2 was associated with LHr, indicating sympathovagal balance), explaining > 99.45% of variance. A linear regression model using PC1 and PC2 under TSM significantly predicted Coma Recovery Scale-Revised (CRS-R) scores (adjusted R 2 = 0.328, p = 0.003), outperforming PPM and BL models. This study establishes TSM-induced HRV as an effective diagnostic biomarker for DOC and links the HRV-based autonomic responses to the CRS-R-based behavioral assessment of consciousness. Clinical Trial Registration: This study was registered as NCT05382260 at ClinicalTrials.gov on March 18, 2022.
Deafness is a prevalent auditory disorder, with a rising incidence attributed to environmental and genetic factors. Although current therapeutic approaches, such as hearing aids and cochlear implants, have made significant contributions to improving the quality of life for hearing-impaired individuals, their effectiveness can be limited in certain situations, highlighting the need for complementary novel treatment strategies to further enhance outcomes. Recent advancements in conductive biomaterials, including graphene, MXene, polypyrrole (PPy), and poly(3,4-ethylenedioxythiophene) (PEDOT), offer transformative potential for auditory therapeutics owing to their exceptional biocompatibility and efficient conductive performance. Electrical stimulation (ES), which modulates the morphology and function of excitable cells, holds promise when integrated with conductive materials. This review synthesizes translational breakthroughs of conductive materials and ES for auditory rehabilitation, focusing on their contributions in the cochlear and their regulatory effects on auditory plasticity. These technologies demonstrate significant potential to promot neuron proliferation, lineage commitment, and maturation, as well as enhance regeneration and recovery after auditory nerve injuries. Furthermore, this article addresses critical challenges in optimizing stable conductive materials, developing effective ES protocols, and ensuring long-term biosafety in vivo. Overall, this review highlights the promising future of conductive materials and ES in advancing auditory therapeutics.
The first clinical descriptions of autism from the late 1960s mentioned sensory dysregulation as one of the commonly reported findings among autistic individuals, yet, it was not until 2013 that they were included as part of the core symptoms of autism spectrum disorder (ASD) in the diagnostic profile, as per the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Abnormal sensory responses are known to be an early clinical feature of ASD, which can severely impact social functioning and also cause some deficits in brain maturation. The lack of understanding of the mechanisms underlying these abnormalities may have caused them to be overlooked in common clinical practice. This review discusses the current knowledge regarding the manner in which different sensory modalities are affected, and the implications they have on the daily functioning of autistic individuals, as well as the possible neural mechanisms underlying them. It was concluded that certain changes can be made in the environment of these individuals that may provide comfort and help them adjust better into society, and further research should be done in this field in order to improve the quality of life of autistic individuals.
