Human hippocampal theta power indicates movement onset and distance travelled

Rodent hippocampal theta-band oscillations are observed throughout translational movement, implicating theta in the encoding of self-motion. Interestingly, increases in theta power are particularly prominent around movement onset. Here, we use intracranial recordings from epilepsy patients navigating in a desktop virtual reality environment to demonstrate that theta power is also increased in the human hippocampus around movement onset and throughout the remainder of movement. Importantly, these increases in theta power are greater both before and during longer paths, directly implicating human hippocampal theta in the encoding of translational movement. These findings help to reconcile previous studies of rodent and human hippocampal theta oscillations and provide additional insight into the mechanisms of spatial navigation in the human brain

Doxylamine-pyridoxine for nausea and vomiting of pregnancy randomized placebo controlled trial: Prespecified analyses and reanalysis

<div><p>Background</p><p>Doxylamine-pyridoxine is recommended as a first line treatment for nausea and vomiting during pregnancy and it is commonly prescribed. We re-analysed the findings of a previously reported superiority trial of doxylamine-pyridoxine for the treatment of nausea and vomiting during pregnancy using the clinical study report obtained from Health Canada.</p><p>Methods and findings</p><p>We re-analysed individual level data for a parallel arm randomized controlled trial that was conducted in six outpatient obstetrical practices in the United States. Pregnant women between 7 and 14 weeks of gestation with moderate nausea and vomiting of pregnancy symptoms. The active treatment was a tablet containing both doxylamine 10 mg and pyridoxine 10 mg taken between 2 and 4 times per day for 14 days depending on symptoms. The control was an identical placebo tablet taken using the same instructions. The primary outcome measure was improvement in nausea and vomiting of symptoms scores using the 13-point pregnancy unique quantification of emesis scale between baseline and 14 days using an ANCOVA. 140 participants were randomized into each group. Data for 131 active treatment participants and 125 control participants were analysed. On the final day of the trial, 101 active treatment participants and 86 control participants provided primary outcome measures.</p><p>There was greater improvement in symptoms scores with doxylamine-pyridoxine compared with placebo (0.73 points; 95% CI 0.21 to 1.25) when last observation carried forward imputation was used for missing data but the difference is not statistically significant using other approaches to missing data (e.g. 0.38; 95% CI -0.08 to 0.84 using complete data).</p><p>Conclusions</p><p>There is a trend towards efficacy for nausea and vomiting symptoms with doxylamine-pyridoxine compared with placebo but the statistical significance of the difference depends on the method of handling missing data and the magnitude of the difference suggests that there is no clinically important benefit employing the prespecified minimal clinically important difference or “expected difference” of 3 points.</p><p>Trial registration</p><p>Clinical Trial <a href="https://clinicaltrials.gov/ct2/show/NCT00614445" target="_blank">NCT00614445</a></p></div

Mean symptom scores on each study day using last observation carried forward imputation.

<p>Mean symptom scores on each study day using last observation carried forward imputation.</p

Selected differences between sources.

<p>Underlines indicate differences. Bolded text indicates consistency with the clinical study report. Italicized text indicates there is an apparent inconsistency with the clinical study report.</p

Results of prespecified and reported analyses.

<p>Results of prespecified and reported analyses.</p

Most frequently reported treatment emergent adverse events and serious adverse events, as reported in clinical study report.

<p>Most frequently reported treatment emergent adverse events and serious adverse events, as reported in clinical study report.</p

Results of different analyses of the primary outcome.

<p>Results of different analyses of the primary outcome.</p

Mean symptom scores on each study day using available cases.

<p>Mean symptom scores on each study day using available cases.</p

CONSORT flow diagram for “ITT-Efficacy” group based on clinical study report (page 6687).

<p>CONSORT flow diagram for “ITT-Efficacy” group based on clinical study report (page 6687).</p

Baseline characteristics of participants.

<p>Baseline characteristics of participants.</p