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Input associativity underlies worry recollection rebirth.
PURPOSE Transcranial magnetic stimulation (TMS) has recently emerged as a noninvasive alternative to the intracarotid sodium amytal (Wada) procedure for establishing hemispheric dominance (HD) for language. The accuracy of HD determined by TMS was examined by comparing against the HD derived by magnetoencephalography (MEG), a prominent clinical technique with excellent concordance with the Wada procedure. METHODS Sixty-seven patients (54 patients ≤18 years) underwent language mapping with TMS and MEG as part of clinical epilepsy and tumor presurgical assessment. Language was mapped in MEG during an auditory word recognition paradigm, and a laterality index was calculated using the number of dipoles and their spatial extent in the two hemispheres. Transcranial magnetic stimulation language mapping was performed as patients performed a naming task, and TMS-induced speech disruptions were recorded during 5-Hz TMS applied to anterior and posterior language cortices. Transcranial magnetic stimulation laterality index was estimated using the number and type of speech disruption in the language regions of each hemisphere. RESULTS Transcranial magnetic stimulation and MEG estimates of HD were concordant in 42 (63%) patients, resulting in a sensitivity of 74% and a specificity of 72%. The overall accuracy of TMS was 73%, equivalent to an odds ratio of 7.35. CONCLUSIONS In this first large-scale comparative study in a clinical population, we demonstrate that TMS is a safe and reliable noninvasive tool in determining HD for language. Improving the accuracy of TMS by optimizing TMS parameters and improving task choice will further facilitate the use of TMS to characterize language function, especially in pediatrics.BACKGROUND Neonatal abstinence syndrome (NAS) is an array of signs and symptoms experienced by a newborn due to abrupt discontinuation of intrauterine exposure to certain drugs, primarily opioids. In the United States, the incidence of NAS has tripled over the last decade. https://www.selleckchem.com/products/bi-1015550.html Current standard of care for drug testing includes the analysis of infant urine and meconium. Sample collection is associated with several limitations, including diaper media interferences, limited sample amount, sample heterogeneity, and the need for professional staff for collection. Umbilical cord tissue has emerged as a convenient sample matrix for testing owing to its universal availability. The purpose of this study was to examine umbilical cords using an untargeted metabolomics approach to determine the detected drugs and validate an analytical method to confirm and quantify the identified drugs. METHODS A metabolomics analysis was performed with 21 umbilical cords to screen for drugs and drug metabolites by liquid chromatography mass spectrometry (LC/MS). Drugs were identified using the NIST database and an analytical method was developed and validated using a secondary LC/MS instrument for positive confirmation and quantitative analysis. RESULTS Twenty-one random umbilical cords from women were tested four were positive for cocaine and the primary and secondary metabolites; one was positive for methadone, the primary metabolite; three were positive for cotinine, the metabolite of nicotine; and five were positive for acetyl norfentanyl. CONCLUSIONS Our research is a prospective method development study using untargeted and targeted approaches to characterize steady-state drug metabolite levels in the umbilical cord matrix at the time of delivery. By characterizing drug type and concentration, this methodology can be utilized to develop a reliable complementary testing method for meconium toxicology screens.Pituitary adenylate cyclase activating polypeptide-38 (PACAP38) may play an important role in primary headaches. Preclinical evidence suggests that PACAP38 modulates trigeminal nociceptive activity mainly through PAC1 receptors while clinical studies report that plasma concentrations of PACAP38 are elevated in spontaneous attacks of cluster headache and migraine and normalize after treatment with sumatriptan. Intravenous infusion of PACAP38 induces migraine-like attacks in migraineurs and cluster-like attacks in cluster headache patients. A rodent-specific PAC1 receptor antibody Ab181 was developed and its effect on nociceptive neuronal activity in the trigeminocervical complex was investigated in vivo in an electrophysiological model relevant to primary headaches. Ab181 is potent and selective at the rat PAC1 receptor and provides near maximum target coverage at 10 mg/kg for more than 48 hours. Without affecting spontaneous neuronal activity, Ab181 effectively inhibits stimulus-evoked activity in the trigeminocervical complex. Immunohistochemical analysis revealed its binding in the trigeminal ganglion and sphenopalatine ganglion but not within the CNS suggesting a peripheral site of action. The pharmacological approach using a specific PAC1 receptor antibody could provide a novel mechanism with a potential clinical efficacy in the treatment of primary headaches.Experimental and clinical data strongly support vagus nerve stimulation (VNS) as a novel treatment in migraine. VNS acutely suppresses cortical spreading depression (CSD) susceptibility, an experimental model that has been used to screen for migraine therapies. However, mechanisms underlying VNS efficacy on CSD are unknown. Here, we interrogated the central and peripheral mechanisms using VNS delivered either invasively (iVNS) or non-invasively (nVNS) in male Sprague-dawley rats. CSD susceptibility was evaluated 40 min after the stimulation. iVNS elevated the electrical CSD threshold more than two-fold and decreased KCl-induced CSD frequency by 22% when delivered to intact vagus nerve. Distal vagotomy did not alter iVNS efficacy (2-fold higher threshold and 19% lower frequency in iVNS vs. sham). In contrast, proximal vagotomy completely abolished iVNS effect on CSD. Pharmacological blockade of nucleus tractus solitarius (NTS), the main relay for vagal afferents, by lidocaine or glutamate receptor antagonist CNQX also prevented CSD suppression by nVNS. Supporting a role for both norepinephrine and serotonin, CSD suppression by nVNS was inhibited by more than 50% after abrogating norepinephrinergic or serotonergic neurotransmission alone using specific neurotoxins; abrogating both completely blocked the nVNS effect. Our results suggest that VNS inhibits CSD through central afferents relaying in NTS and projecting to subcortical neuromodulatory centers providing serotonergic and norepinephrinergic innervation to the cortex.
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