Neural effects of TMS trains on the human prefrontal cortex.

How does a train of TMS pulses modify neural activity in humans? Despite adoption of repetitive TMS (rTMS) for the treatment of neuropsychiatric disorders, we still do not understand how rTMS changes the human brain. This limited understanding stems in part from a lack of methods for noninvasively measuring the neural effects of a single TMS train-a fundamental building block of treatment-as well as the cumulative effects of consecutive TMS trains. Gaining this understanding would provide foundational knowledge to guide the next generation of treatments.

Direct cortical stimulation induces short-term plasticity of neural oscillations in humans.

Patterned brain stimulation is commonly employed as a tool for eliciting plasticity in brain circuits and treating neuropsychiatric disorders. Although widely used in clinical settings, there remains a limited understanding of how stimulation-induced plasticity influences neural oscillations and their interplay with the underlying baseline functional architecture. To address this question, we applied 15 minutes of 10Hz focal electrical simulation, a pattern identical to 'excitatory' repetitive transcranial magnetic stimulation (rTMS), to 14 medically-intractable epilepsy patients undergoing intracranial electroencephalographic (iEEG).

Associations of handgrip weakness and asymmetry with new-onset stroke in Chinese middle-aged and older adults: a cohort study.

Background: Weak handgrip strength (HGS) has been linked to adverse health outcomes including stroke. However, the joint associations of HGS weakness and asymmetry between limbs with stroke incidence remain underexplored.

Methods: This cohort study analyzed data of participants aged ≥45 years from three waves (2011, 2013, and 2015) of the China Health and Retirement Longitudinal Study.

miR-431 secreted by human vestibular schwannomas increases the mammalian inner ear's vulnerability to noise trauma.

Introduction: Vestibular schwannoma (VS) is an intracranial tumor that arises on the vestibular branch of cranial nerve VIII and typically presents with sensorineural hearing loss (SNHL). The mechanisms of this SNHL are postulated to involve alterations in the inner ear's microenvironment mediated by the genetic cargo of VS-secreted extracellular vesicles (EVs). We aimed to identify the EV cargo associated with poor hearing and determine whether its delivery caused hearing loss and cochlear damage in a mouse model

Methods: VS tissue was collected from routinely resected tumors of patients with good (VS-GH) or poor (VS-PH) pre-surgical hearing measured via pure-tone average and word recognition scores.

Transthalamic input to higher-order cortex selectively conveys state information.

Communication among different neocortical areas is largely thought to be mediated by long-range synaptic interactions between cortical neurons, with the thalamus providing only an initial relay of information from the sensory periphery. Higher-order thalamic nuclei receive strong synaptic inputs from the cortex and send robust projections back to other cortical areas, providing a distinct and potentially critical route for cortico-cortical communication. However, the relative contributions of corticocortical and thalamocortical inputs to higher-order cortical function remain unclear.

Promoting Surgeon-Scientists in Otolaryngology-Head and Neck Surgery-From Bench to Bedside.

Importance: Surgeon-scientists (defined as principal investigators [PIs] with a Doctor of Medicine [MD] degree or a combined MD and Doctor of Philosophy [PhD] degree) in otolaryngology-head and neck surgery (OHNS) are imperative for achieving clinical translation in the OHNS field.

Objective: To (1) raise awareness about the current state of surgeon-scientists in OHNS, (2) contextualize the landscape of surgeon-scientists in OHNS by comparing it to those of neurosurgery and ophthalmology, and (3) identify strategies for attracting and retaining surgeon-scientists in OHNS.

Evidence Review: Research funding data from fiscal years 2015 to 2021 among surgeon-scientists in OHNS, neurosurgery, and ophthalmology were obtained from the National Institutes of Health (NIH) Research Portfolio Online Reporting Tools Expenditures and Results and the US Department of Defense (DOD) Congressionally Directed Medical Research Programs awards database.

Immune Profiling of Secreted Factors from Human Vestibular Schwannoma Cells and Tumor-associated Macrophages.

Objectives: This study compared the immune-related secretory capacity of human vestibular schwannoma (VS) and tumor-assisted macrophages (TAMs) with their normal counterparts (Schwann cells [SC] and peripheral blood monocyte-derived macrophages [Mo-MFs], respectively), and examined relationships with presurgical hearing and tumor size.

Methods: VS tumors (n = 16), auditory nerve (n = 1), blood (n = 9), and great auricular nerves (n = 3) were used. SCs (S100B ) and TAMs (CD68 ) were isolated from VS tissue for culture.

Curved adhesions mediate cell attachment to soft matrix fibres in three dimensions.

Integrin-mediated focal adhesions are the primary architectures that transmit forces between the extracellular matrix (ECM) and the actin cytoskeleton. Although focal adhesions are abundant on rigid and flat substrates that support high mechanical tensions, they are sparse in soft three-dimensional (3D) environments. Here we report curvature-dependent integrin-mediated adhesions called curved adhesions.

Lateral hypothalamus hypocretin/orexin glucose-inhibited neurons promote food seeking after calorie restriction.

Objective: The present study tests the hypothesis that changes in the glucose sensitivity of lateral hypothalamus (LH) hypocretin/orexin glucose-inhibited (GI) neurons following weight loss leads to glutamate plasticity on ventral tegmental area (VTA) dopamine neurons and drives food seeking behavior.

Methods: C57BL/6J mice were calorie restricted to a 15% body weight loss and maintained at that body weight for 1 week. The glucose sensitivity of LH hypocretin/orexin GI and VTA dopamine neurons was measured using whole cell patch clamp recordings in brain slices.

Bayesian dynamical system analysis of the effects of methylphenidate in children with attention-deficit/hyperactivity disorder: a randomized trial.

Methylphenidate is a widely used and effective treatment for attention-deficit/hyperactivity disorder (ADHD), yet the underlying neural mechanisms and their relationship to changes in behavior are not fully understood. Specifically, it remains unclear how methylphenidate affects brain and behavioral dynamics, and the interplay between these dynamics, in individuals with ADHD. To address this gap, we used a novel Bayesian dynamical system model to investigate the effects of methylphenidate on latent brain states in 27 children with ADHD and 49 typically developing children using a double-blind, placebo-controlled crossover design.

A NanoCurvS platform for quantitative and multiplex analysis of curvature-sensing proteins.

The cell membrane is characterized by a rich variety of topographical features such as local protrusions or invaginations. Curvature-sensing proteins, including the Bin/Amphiphysin/Rvs (BAR) or epsin N-terminal homology (ENTH) family proteins, sense the bending sharpness and the positive/negative sign of these topographical features to induce subsequent intracellular signaling. A number of assays have been developed to study curvature-sensing properties of proteins , but it is still challenging to probe low curvature regime with the diameter of curvature from hundreds of nanometers to micrometers.

Potential Ototoxicity of Insulin-like Growth Factor 1 Receptor Signaling Inhibitors: An In Silico Drug Repurposing Study of the Regenerating Cochlear Neuron Transcriptome.

Spiral ganglion neurons (SGNs) connect cochlear hair cells with higher auditory pathways and their degeneration due to drug toxicity (ototoxicity) contributes to hearing loss. This study aimed to identify drug classes that are negatively correlated with the transcriptome of regenerating SGNs. Human orthologs of differentially expressed genes within the regenerating neonatal mouse SGN transcriptome were entered into CMap and the LINCS unified environment and perturbation-driven gene expression was analyzed.

Both reactive and proactive control are deficient in children with ADHD and predictive of clinical symptoms.

Cognitive control deficits are a hallmark of attention deficit hyperactivity disorder (ADHD) in children. Theoretical models posit that cognitive control involves reactive and proactive control processes but their distinct roles and inter-relations in ADHD are not known, and the contributions of proactive control remain vastly understudied. Here, we investigate the dynamic dual cognitive control mechanisms associated with both proactive and reactive control in 50 children with ADHD (16F/34M) and 30 typically developing (TD) children (14F/16M) aged 9-12 years across two different cognitive controls tasks using a within-subject design.

A generalizable functional connectivity signature characterizes brain dysfunction and links to rTMS treatment response in cocaine use disorder.

Cocaine use disorder (CUD) is a prevalent substance abuse disorder, and repetitive transcranial magnetic stimulation (rTMS) has shown potential in reducing cocaine cravings. However, a robust and replicable biomarker for CUD phenotyping is lacking, and the association between CUD brain phenotypes and treatment response remains unclear. Our study successfully established a cross-validated functional connectivity signature for accurate CUD phenotyping, using resting-state functional magnetic resonance imaging from a discovery cohort, and demonstrated its generalizability in an independent replication cohort.

The pathotome and precision health.

This scientific commentary refers to ‘Pathological combinations in neurodegenerative disease are heterogeneous and disease-associated’ by Robinson (https://doi.org/10.1093/brain/awad059).

Comparative Transcriptomic Analysis of Archival Human Vestibular Schwannoma Tissue from Patients with and without Tinnitus.

Vestibular schwannoma (VS) is an intracranial tumor that commonly presents with tinnitus and hearing loss. To uncover the molecular mechanisms underlying VS-associated tinnitus, we applied next-generation sequencing (Illumina HiSeq) to formalin-fixed paraffin-embedded archival VS samples from nine patients with tinnitus (VS-Tin) and seven patients without tinnitus (VS-NoTin). Bioinformatic analysis was used to detect differentially expressed genes (DEG; i.

Curved adhesions mediate cell attachment to soft matrix fibres in 3D.

Mammalian cells adhere to the extracellular matrix (ECM) and sense mechanical cues through integrin-mediated adhesions . Focal adhesions and related structures are the primary architectures that transmit forces between the ECM and the actin cytoskeleton. Although focal adhesions are abundant when cells are cultured on rigid substrates, they are sparse in soft environments that cannot support high mechanical tensions .

Noise-Induced Hearing Loss.

Noise-induced hearing loss (NIHL) is the second most common cause of sensorineural hearing loss, after age-related hearing loss, and affects approximately 5% of the world's population. NIHL is associated with substantial physical, mental, social, and economic impacts at the patient and societal levels. Stress and social isolation in patients' workplace and personal lives contribute to quality-of-life decrements which may often go undetected.

Associations of Tinnitus Incidence with Use of Tumor Necrosis Factor-Alpha Inhibitors among Patients with Autoimmune Conditions.

Tumor necrosis factor-alpha (TNFα) may promote neuroinflammation prompting tinnitus. This retrospective cohort study evaluated whether anti-TNFα therapy influences incident tinnitus risk among adults with autoimmune disorders and no baseline tinnitus selected from a US electronic health records database (Eversana; 1 January 2010-27 January 2022). Patients with anti-TNFα had ≥90-day history pre-index (first autoimmune disorder diagnosis) and ≥180-day follow-up post-index.

Reliability and Validity of Transcranial Magnetic Stimulation-Electroencephalography Biomarkers.

Noninvasive brain stimulation and neuroimaging have revolutionized human neuroscience with a multitude of applications, including diagnostic subtyping, treatment optimization, and relapse prediction. It is therefore particularly relevant to identify robust and clinically valuable brain biomarkers linking symptoms to their underlying neural mechanisms. Brain biomarkers must be reproducible (i.

Cortical plasticity differences in substance use disorders.

Among substances, opiates and psychostimulants are responsible for the most significant public health problems, yet few studies have characterized their similarities or differences in the cortical plasticity of individuals with these substance related problems. This investigation utilized concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to examine cortical plasticity characteristics of individuals with heroin and methamphetamine related substance use disorder (SUD) relative to healthy controls. TMS-EEG data were collected from healthy control subjects ( = 35), subjects with heroin ( = 72) and methamphetamine ( = 69) use disorder.

Optogenetic stimulation of anterior insular cortex neurons in male rats reveals causal mechanisms underlying suppression of the default mode network by the salience network.

The salience network (SN) and default mode network (DMN) play a crucial role in cognitive function. The SN, anchored in the anterior insular cortex (AI), has been hypothesized to modulate DMN activity during stimulus-driven cognition. However, the causal neural mechanisms underlying changes in DMN activity and its functional connectivity with the SN are poorly understood.