The mouse has become an important model system for studying the cellular basis of learning and coding of heading by the vestibular system. Here we recorded from single neurons in the vestibular nuclei to understand how vestibular pathways encode self-motion under natural conditions, during which proprioceptive and motor-related signals as well as vestibular inputs provide feedback about an animal's movement through the world. We recorded neuronal responses in alert behaving mice focusing on a group of neurons, termed vestibular-only cells, that are known to control posture and project to higher-order centers. We found that the majority (70%, n = 21/30) of neurons were bimodal, in that they responded robustly to passive stimulation of proprioceptors as well as passive stimulation of the vestibular system. Additionally, the linear summation of a given neuron's vestibular and neck sensitivities predicted well its responses when both stimuli were applied simultaneously. In contrast, neuronal responses were suppressed when the same motion was actively generated, with the one striking exception that the activity of bimodal neurons similarly and robustly encoded head on body position in all conditions. Our results show that proprioceptive and motor-related signals are combined with vestibular information at the first central stage of vestibular processing in mice. We suggest that these results have important implications for understanding the multisensory integration underlying accurate postural control and the neural representation of directional heading in the head direction cell network of mice.
Chronic migraine is a relatively newly recognized disease. We have an increasing number of medications studied specifically in chronic migraines, and these are briefly introduced. Additionally, there are guidelines to help design trials in chronic migraine. A valid future research question is to further study the efficacy of the medications studied in an undifferentiated migraine population, as there is economic pressure to use these medications as first line.
Objective We used network meta‐analysis (NMA) to characterize the relative effectiveness and harms of acute treatment options for cluster headache. Background There are few evidence‐based acute treatments available for cluster headache. As most treatments were compared only against placebos in clinical trials, few head‐to‐head comparisons of treatments are available. Methods An a priori registered scoping review was performed to identify randomized controlled trials evaluating treatments in adult patients (>18 years old) with cluster headache per accepted diagnostic criteria. Bayesian NMAs were performed to compare treatments in terms of headache relief at 15 or 30 min, and also the occurrence of adverse events. We report odds ratios (ORs) of relative treatment effects along with corresponding 95% credible intervals (CrIs), as well as measures of treatment ranking. Results A total of 13 randomized controlled trials informed NMAs. We found high flow oxygen to be the most effective therapy for headache response at 15 and 30 min (OR 9.0, 95% CrI 5.3 to 15.9 vs. placebo), with injectable sumatriptan demonstrating the next highest effect (OR 6.4, 95% CrI 3.75 to 11.1 vs. placebo). High flow oxygen was also more effective than low flow oxygen (OR 2.55, 95% CrI 1.13 to 5.8), nasal spray zolmitriptan (OR 3.75, 95% CrI 1.72 to 8.4), octreotide (OR 4.5, 95% CrI 1.64 to 12.5), and non‐invasive vagal nerve stimulation (nVNS; OR 5.2, 95% CrI 2.29 to 11.9). Sumatriptan injectable was also effective for headache relief and was found to be better than nasal spray zolmitriptan (OR 2.67, 95% CrI 1.21 to 5.9), octreotide (OR 3.20, 95% CrI 1.17 to 8.8), and nVNS (OR 3.69, 95% CrI 1.63 to 8.4). Octreotide (OR 4.1, 95% CrI 1.71 to 10.5) and sumatriptan (OR 2.40, 95% CrI 1.39 to 4.2) were associated with greater risk of adverse events compared to placebo, while other treatments did not demonstrate increased risk. When focusing on patients with episodic cluster headache, nVNS was significantly better than placebo (OR 4.9, 95% CrI 1.89 to 14.1). Conclusions Our findings suggest that high flow oxygen is more efficacious when compared to low flow oxygen for headache relief. When low flow oxygen fails in patients who can tolerate oxygen, increased flow rates should be tried. Additionally, high flow oxygen is likely more effective than zolmitriptan nasal spray, nVNS, and octreotide. Sumatriptan injectable is more likely to be effective when compared to zolmitriptan nasal spray, octreotide, and nVNS.
Background: Cluster headache is the most common primary headache disorder of the trigeminal autonomic cephalalgias, and it is highly disabling.Objective: We undertake a scoping review to characterize therapies to prevent and acutely treat cluster headache, characterize trial methodology utilized in studies, and recommend future trial "good practices." We also assess homogeneity of studies and feasibility for future network meta-analyses (NMAs) to compare acute and preventive treatments for cluster headache. Methods:A priori protocol for this scoping review was registered and available on Open Science Forum. We sought studies that enrolled adult patients with cluster headache as identified by accepted diagnostic criteria. Both randomized controlled trials (RCTs) and observational studies (with a control group) were included. The interventions of interest were medications, procedures, devices, surgeries, and behavioral/psychological interventions, whereas comparators of interest were placebo, sham, or other active treatments.Outcomes were predefined; however, we did not exclude studies lacking these outcomes.A systemic search was conducted in Ovid Medline, Embase, and Cochrane. We performed a targeted search for conference abstracts from journals prominent in the field. Results:We identified 56 studies: 45 RCTs, four studies only available in clinical trial registries, and seven observational studies. Of the 45 RCTs, 20 focused on acute therapies and 25 on preventive therapies. Overall, we determined that it is feasible to pursue a NMA for acute therapy focusing on 15 or 30-min headache reduction for acute trials, as we identified 11 trials in the combined population of patients with either episodic or chronic cluster headache (2 trials in populations with chronic cluster headache were also found). For preventive therapy of cluster headache, we identified trials with common outcomes that may be considered for NMA, however, as these trials had differences in treatment effect modifiers that could not be corrected, NMAs appear infeasible for this indication. We identified new studies looking at noninvasive vagal nerve stimulation, sphenopalatine ganglion stimulation, prednisone, and oxygen published since the most recent systematic review in the field, although these acute treatments were previously identified as effective. However, for calcitonin gene-related Rationale for this workThere are few evidence-based treatments available in CH, 3,4 as it is a condition that has been under studied. 1 The current scoping review was designed to expand upon past reviews in several ways. First, we sought to identify new studies published since the prior reviews were completed. 3,4 Second, with the data gathered in this scoping review, we aimed to assess the feasibility of pursuing network metaanalyses (NMAs) 5,6 to inform comparisons of multiple treatments based on available direct and indirect evidence in the field. We planned to systematically evaluate study and population features to establish the potential for rigorous N...
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