Animal behavior emerges from collective dynamics of neurons, making it vulnerable to damage. Paradoxically, many organisms exhibit a remarkable ability to maintain significant behavior even after large-scale neural injury. Molecular underpinnings of this extreme robustness remain largely unknown. Here, we develop a quantitative pipeline to measure long-lasting latent states in planarian flatworm behaviors during whole-brain regeneration. By combining >20,000 animal trials with neural network modeling, we show that long-range volumetric peptidergic signals allow the planarian to rapidly restore coarse behavior output after large perturbations to the nervous system, while slow restoration of small-molecule neuromodulator functions refines precision. This relies on the different time and length scales of neuropeptide and small-molecule transmission to generate incoherent patterns of neural activity that competitively regulate behavior. Controlling behavior through opposing communication mechanisms creates a more robust system than either alone and may serve as a generalizable approach for constructing robust neural networks.

Biotin and arginine play crucial roles in lipid metabolism and may offer promising interventions against obesity. This study examined the combined effect of magnesium biotinate (MgB) and inositol-stabilized arginine silicate complex (ASI) on obesity-related oxidative imbalance, inflammation, lipid metabolism and neuromodulation in rats on a high-fat diet (HFD). Forty rats were divided into five groups: (a) control: rats were fed a standard diet containing 12% of energy from fat; (b) HFD: rats were fed the HFD with 42% of energy from fat; (c) HFD + MgB: rats were fed the HFD and given 0.31 mg/kg body weight (BW) MgB, (d) HFD + ASI: rats were fed the HFD and were given 12.91 mg/kg BW ASI), and (e) HFD + MgB + ASI: rats were fed the HFD and given 0.31 mg/kg BW MgB and 12.91 mg/kg BW ASI). The combined administration of MgB and ASI reduced the levels of serum cholesterol, free fatty acid (FFA), and malondialdehyde (MDA), as well as liver inflammatory cytokines, sterol regulatory element-binding protein 1-c (SREBP-1c), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) proteins (P < 0.001) compared to HFD rats without supplementation. Moreover, this combination increased the activities of antioxidant enzymes (P < 0.05) and boosted the brain-derived neurotrophic factor (BDNF), serotonin, dopamine (P < 0.001), as well as liver insulin receptor substrate 1 (IRS-1) and peroxisome proliferator-activated receptor gamma (PPAR-γ) (P < 0.001). These findings suggest that combining MgB and ASI could deter liver fat accumulation and enhance lipid metabolism in HFD-fed rats by modulating various metabolic pathways and neuromodulators related to energy metabolism. This combination demonstrates potential in addressing obesity and its related metabolic dysfunctions.

BACKGROUND: Neurogenic cough (NC) is thought to be related to sensory neuropathy in the hypopharynx and larynx. Defined as a cough persisting longer than 8 weeks refractory to standard therapy, it is a diagnosis of exclusion when other common etiologies (asthma, gastroesophageal reflux disease (GERD), medication side effects) are ruled out. It affects roughly 11 % of Americans and can negatively impact quality of life.
METHODS: Following institutional review board approval, we evaluated the medical records of adult patients seen at the University of Arizona\'s tertiary laryngology center from 2018 to 2023. Patients were included if their cough persisted for >8 weeks, and they either did not respond to prior proton pump inhibitor and asthma therapy or had GERD and asthma ruled out. These patients underwent a progressive escalation of therapy, which included neuromodulators with or without cough suppression therapy, superior laryngeal nerve (SLN) block, and laryngeal botulinum toxin injections. The primary outcome was patient-reported improvement in cough symptoms rated on a 1-5 scale: 1 = no response, 2 = mild improvement, 3 = moderate improvement, 4 = significant improvement, 5 = complete resolution.
RESULTS: A total of 56 patients were included. Mean (SD) age was 64.6 (14.8) years, and 66 % were female. Overall, 42 patients (75.0 %) responded to treatment. Among responders, 7 (16.7 %) experienced mild improvement, 14 (33.3 %) experienced moderate improvement, 17 (40.5 %) experienced significant improvement, and 4 (9.5 %) experienced complete resolution of their cough. 33 patients (58.9 %) were managed exclusively with neuromodulators ± cough suppression therapy; 27 responded, with an average response rating of 3.0 (SD = 1.2). 11 patients (19.6 %) failed medical therapy and underwent SLN block without subsequent botox treatment; 7 responded, with an average response rating of 2.5 (SD = 1.4). 9 patients (16.1 %) failed all previous therapies and underwent laryngeal botulinum toxin injections; 6 responded with an average response rating of 2.4 (SD = 1.3). The remaining 3 patients underwent cough suppression therapy alone, with 2 responding and an average response rating of 3.3 (SD = 1.7).
CONCLUSIONS: Neurogenic cough can be effectively treated with a stepwise multimodal approach, including neuromodulators, cough suppression therapy, SLN block, and laryngeal botulinum toxin injections.

METHODS: The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update (CPU) is to review the available evidence and provide expert advice regarding the diagnosis and management of cyclic vomiting syndrome.
METHODS: This CPU was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. This expert commentary incorporates important as well as recently published studies in this field, and it reflects the experiences of the authors who are experts in treating patients with cyclic vomiting syndrome.

OBJECTIVE: Physical activity (PA) is a key component for brain health and Reserve, and it is among the main dementia protective factors. However, the neurobiological mechanisms underpinning Reserve are not fully understood. In this regard, a noradrenergic (NA) theory of cognitive reserve (Robertson, 2013) has proposed that the upregulation of NA system might be a key factor for building reserve and resilience to neurodegeneration because of the neuroprotective role of NA across the brain. PA elicits an enhanced catecholamine response, in particular for NA. By increasing physical commitment, a greater amount of NA is synthetised in response to higher oxygen demand. More physically trained individuals show greater capabilities to carry oxygen resulting in greater Vo 2 max - a measure of oxygen uptake and physical fitness (PF).
METHODS: We hypothesized that greater Vo 2 max would be related to greater Locus Coeruleus (LC) MRI signal intensity. In a sample of 41 healthy subjects, we performed Voxel-Based Morphometry analyses, then repeated for the other neuromodulators as a control procedure (Serotonin, Dopamine and Acetylcholine).
RESULTS: As hypothesized, greater Vo 2 max related to greater LC signal intensity, and weaker associations emerged for the other neuromodulators.
CONCLUSIONS: This newly established link between Vo 2 max and LC-NA system offers further understanding of the neurobiology underpinning Reserve in relationship to PA. While this study supports Robertson\'s theory proposing the upregulation of the NA system as a possible key factor building Reserve, it also provides ground for increasing LC-NA system resilience to neurodegeneration via Vo 2 max enhancement.

BACKGROUND: The use of neuromodulators is prevalent in various functional gastrointestinal disease. However, data concerning the outcomes of these treatments in functional esophageal disorders (FED) remains limited and inadequate.
OBJECTIVE: The aim of the present study is to examine the efficacy of central neuromodulators in FED.
METHODS: We searched PubMed, EMBASE, and the Cochrane library databases from inception to April 2023. Randomized controlled trials that compared the effects of neuromodulators and placebos on FED are included. Primary outcome is the symptom improvement, and Rome IV criteria is used to assess eligible studies.
RESULTS: Eleven randomized controlled studies (three for functional chest pain, four for reflux hypersensitivity/functional heartburn, three for globus, and one for functional dysphagia) were included in the final analysis. Neuromodulators reduced chest pain by 52%-71% in patients with functional chest pain, and alleviated symptom by 46%-75% in patients with globus (n = 3, Odds ratio 6.30, 95% confidence interval 4.17-9.50). However, the results were inconsistent for reflux hypersensitivity and functional heartburn. There was a lack of convincing evidence to support the use of neuromodulators for functional dysphagia. The use of neuromodulators did not have a significant impact on the quality of life.
CONCLUSIONS: Functional chest pain and globus may potentially benefit from the use of neuromodulators, but their effectiveness for functional dysphagia, functional heartburn and reflux hypersensitivity remains controversial. More controlled trials are needed to confirm the therapeutic effects on these conditions.

Sensorimotor computation integrates bottom-up world state information with top-down knowledge and task goals to form action plans. In the rodent whisker system, a prime model of active sensing, evidence shows neuromodulatory neurotransmitters shape whisker control, affecting whisking frequency and amplitude. Since neuromodulatory neurotransmitters are mostly released from subcortical nuclei and have long-range projections that reach the rest of the central nervous system, mapping the circuits of top-down neuromodulatory control of sensorimotor nuclei will help to systematically address the mechanisms of active sensing. Therefore, we developed a neuroinformatic target discovery pipeline to mine the Allen Institute\'s Mouse Brain Connectivity Atlas. Using network connectivity analysis, we identified new putative connections along the whisker system and anatomically confirmed the existence of 42 previously unknown monosynaptic connections. Using this data, we updated the sensorimotor connectivity map of the mouse whisker system and developed the first cell-type-specific map of the network. The map includes 157 projections across 18 principal nuclei of the whisker system and neuromodulatory neurotransmitter-releasing. Performing a graph network analysis of this connectome, we identified cell-type specific hubs, sources, and sinks, provided anatomical evidence for monosynaptic inhibitory projections into all stages of the ascending pathway, and showed that neuromodulatory projections improve network-wide connectivity. These results argue that beyond the modulatory chemical contributions to information processing and transfer in the whisker system, the circuit connectivity features of the neuromodulatory networks position them as nodes of sensory and motor integration.

UNASSIGNED: Increasing evidence over the last decade suggests that many cases of unexplained chronic cough (UCC) have a neurogenic etiology, with laryngeal hypersensitivity (LH) being identified as a key mechanism. Official guidelines since 2015 have adopted use of neuromodulators and adjuvant speech therapy as a result, but historically implementation of guidelines is slow. Our survey aimed to investigate gaps in diagnosis and management practices of otolaryngology providers in caring for patients with UCC.
UNASSIGNED: Cross-sectional study.
UNASSIGNED: Survey.
UNASSIGNED: 12-item survey was distributed to 110 otolaryngology practitioners experienced in diagnosis and treatment of chronic cough at a regional otolaryngology continuing education conference. Statistical analysis included Kendall\'s Tau Rank Correlation to measure the ordinal association between responses to questions, and Fisher\'s exact test to determine if there were associations between responses and years of career experience.
UNASSIGNED: Forty eligible respondents underwent subsequent analysis. There was no association between frequency of identifying LH as a primary etiology and use of neuromodulators (τ = 0.23, P = .10). However, there was a significant correlation between LH and referrals to speech therapy (τ = 0.27, P = .05). Fisher\'s exact test did not reveal any significant differences among any responses based on practitioner experience.
UNASSIGNED: Our results indicate a possible disparity in treatment of UCC with neuromodulators and the utilization of speech therapy despite guideline recommendations advocating for neuromodulators with adjuvant speech therapy. Further research with larger sample sizes and more specific inquiries is necessary to elucidate this association and control for any regional differences.

Pain is a common symptom among patients with inflammatory bowel disease (IBD). Although pain typically occurs during episodes of inflammation, it is also commonly experienced when intestinal inflammation is quiescent. Many gastroenterologists are at a loss how to approach pain symptoms when they occur in the absence of gut inflammation. We provide guidance in this area as to the evaluation, diagnosis, and treatment of pain among patients with IBD.
This CPU was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. This expert commentary incorporates important as well as recently published studies in this field, and it reflects the experiences of the authors. Formal ratings regarding the quality of evidence or strength of the presented considerations were not included because systematic reviews were not performed.

BACKGROUND: Botulinum toxin injections are widely sought after in the field of medical aesthetics, offering consumers a variety of brand choices. Two commonly available botulinum toxin products, onabotulinumtoxinA and neubotulinumtoxinA, are featured in numerous clinics, leading many to question whether there are discernible differences in results, given their varying price ranges.
OBJECTIVE: To evaluate the efficacy and safety of neubotulinumtoxinA for the treatment of forehead horizontal lines.
METHODS: A 12-week prospective, single-centre, interventional split-face study was conducted, including 30 subjects. These enrolled subjects received a single treatment session, with neubotulinumtoxinA applied to the left side of the forehead and onabotulinumtoxinA to the right side. A superficial injection was performed in all individuals, where the product was injected subdermally in the frontalis muscle. Evaluation was conducted at baseline, 7 days, 14, days and 4, 8, and 12 weeks after treatment, both when the eyebrows were at maximum lift and in a resting position. Treatment efficacy was assessed by two physicians and self-assessed by the patients, using the Fitzpatrick Wrinkle Classification system. Adverse events were documented to evaluate safety.
RESULTS: The study found no statistically significant difference in the efficacy of neubotulinum and onabotulinum for treating forehead wrinkles, as indicated by p-values above 0.05 for both static and dynamic conditions. No safety and adverse events were observed in both formulations.
CONCLUSIONS: This study has demonstrated that neither formulation is inferior to each other in the treatment of forehead horizontal lines.