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The introduction of monoclonal antibodies (mAbs) directed against the calcitonin gene-related peptide (CGRP), or its receptor (CGRPr), revolutionized migraine management due to their high efficacy and few side effects. Data suggest that the CGRP may even be implicated in circadian rhythm, but studies about the effect of anti-CGRP treatments on sleep are still lacking. The aim of the present study was to assess the effect of erenumab (70 and 140 mg per month), a human mAb directed against CGRPr, on chronotype in chronic migraineurs; secondly, we assessed its efficacy, safety, and the effects on anxiety and depression. Sleep was evaluated using self-administrable questionnaires investigating chronotype, sleep quality, and daytime sleepiness. Migraine diaries and several self-administrable questionnaires regarding headache impact and psychological correlates were evaluated every 3 months during 12 months of treatment. Eighty-eight patients were included; most of them showed a significant reduction in headache frequency and an improvement in psychological symptoms. Moreover, an initial change in chronotype was observed at the three-month assessment from a morning chronotype to an intermediate one; a similar trend remained in the other evaluations, even if it did not reach a statistical significance. Lastly, patients who responded to the treatment showed a progressive sleep efficiency reduction. The present real-life study hypothesized the influence of erenumab on chronotype, representing a link between circadian rhythm, CGRP, and migraine.

During wakeful rest, individuals make small eye movements during fixation. We examined how these endogenously driven oculomotor patterns impact topography and topology of functional brain networks. We used a dataset consisting of eyes-open resting-state (RS) fMRI data with simultaneous eye tracking. The eye-tracking data indicated minor movements during rest, which correlated modestly with RS BOLD data. However, eye-tracking data correlated well with echo-planar imaging time series sampled from the area of the eye-orbit (EO-EPI), which is a signal previously used to identify eye movements during exogenous saccades and movie viewing. Further analyses showed that EO-EPI data were correlated with activity in an extensive motor and sensorimotor network, including components of the dorsal attention network and the frontal eye fields. Partialling out variance related to EO-EPI from RS data reduced connectivity, primarily between sensorimotor and visual areas. It also produced networks with higher modularity, lower mean connectivity strength, and lower mean clustering coefficient. Our results highlight new aspects of endogenous eye movement control during wakeful rest. They show that oculomotor-related contributions form an important component of RS network topology, and that those should be considered in interpreting differences in network structure between populations or as a function of different experimental conditions., (© 2021 Massachusetts Institute of Technology.)

When available, people use prior knowledge to predict dimensions of future events such as their location and semantic features. However, few studies have examined how multi-dimensional predictions are implemented, and mechanistic accounts are absent. Using eye tracking, we evaluated whether predictions of target-location and target-category interact during the earliest stages of orientation. We presented stochastic series so that across four conditions, participants could predict either the location of the next target-image, its semantic category, both dimensions, or neither. Participants observed images in absence of any task involving their semantic content. We modeled saccade latencies using ELATER, a rise-to-threshold model that accounts for accumulation rate (AR), variance of AR over trials, and variance of decision baseline. The main findings were: 1) AR scaled with the degree of surprise associated with a target's location; 2) predictability of semantic-category hindered saccade latencies, suggesting a bottleneck in implementing joint predictions; 3) saccades to targets that satisfied semantic expectations were associated with greater AR-variance than saccades to semantically-surprising images, consistent with a richer repertoire of early evaluative processes for semantically-expected images. Predictability of target-category also impacted gaze pre-positioning prior to target presentation. The results indicate a strong interaction between foreknowledge of object location and semantics during stimulus-guided saccades, and suggest statistical regularities in an input stream can also impact anticipatory, non-stimulus-guided processes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A core question underlying neurobiological and computational models of behavior is how individuals learn environmental statistics and use them to make predictions. Most investigations of this issue have relied on reactive paradigms, in which inferences about predictive processes are derived by modeling responses to stimuli that vary in likelihood. Here we deployed a novel anticipatory oculomotor metric to determine how input statistics impact anticipatory behavior that is decoupled from target-driven-response. We implemented transition constraints between target locations, so that the probability of a target being presented on the same side as the previous trial was 70% in one condition (pret70) and 30% in the other (pret30). Rather than focus on responses to targets, we studied subtle endogenous anticipatory fixation offsets (AFOs) measured while participants fixated the screen center, awaiting a target. These AFOs were small (<0.4° from center on average), but strongly tracked global-level statistics. Speaking to learning dynamics, trial-by-trial fluctuations in AFO were well-described by a learning model, which identified a lower learning rate in pret70 than pret30, corroborating prior suggestions that pret70 is subjectively treated as more regular. Most importantly, direct comparisons with saccade latencies revealed that AFOs: (a) reflected similar temporal integration windows, (b) carried more information about the statistical context than did saccade latencies, and (c) accounted for most of the information that saccade latencies also contained about inputs statistics. Our work demonstrates how strictly predictive processes reflect learning dynamics, and presents a new direction for studying learning and prediction.

When a neuron responds to a sensory stimulus, two fundamental codes [1-6] may transmit the information specifying stimulus identity--spike rate (the total number of spikes in the sequence, normalized by time) and spike timing (the detailed millisecond-scale temporal structure of the response). To assess the functional significance of these codes, we recorded neuronal responses in primary (S1) and secondary (S2) somatosensory cortex of five rats as they used their whiskers to identify textured surfaces. From the spike trains evoked during whisker contact with the texture, we computed the information that rate and timing codes carried about texture identity and about the rat's choice. S1 and S2 spike timing carried more information about stimulus and about choice than spike rates; the conjunction of rate and timing carried more information than either code alone. Moreover, on trials when our spike-timing-decoding algorithm extracted faithful texture information, the rat was more likely to choose correctly; when our spike-timing-decoding algorithm extracted misleading texture information, the rat was more likely to err. For spike rate information, the relationship between faithfulness of the message and correct choice was significant but weaker. These results indicate that spike timing makes crucial contributions to tactile perception, complementing and surpassing those made by rate. The language by which somatosensory cortical neurons transmit information, and the readout mechanism used to produce behavior, appears to rely on multiplexed signals from spike rate and timing., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Fusing left and right eye images into a single view is dependent on precise ocular alignment, which relies on coordinated eye movements. During movements of the head this alignment is maintained by numerous reflexes. Although rodents share with other mammals the key components of eye movement control, the coordination of eye movements in freely moving rodents is unknown. Here we show that movements of the two eyes in freely moving rats differ fundamentally from the precisely controlled eye movements used by other mammals to maintain continuous binocular fusion. The observed eye movements serve to keep the visual fields of the two eyes continuously overlapping above the animal during free movement, but not continuously aligned. Overhead visual stimuli presented to rats freely exploring an open arena evoke an immediate shelter-seeking behaviour, but are ineffective when presented beside the arena. We suggest that continuously overlapping visual fields overhead would be of evolutionary benefit for predator detection by minimizing blind spots.

Different time-frequency techniques may be used to investigate the relation between latency and frequency of transient-evoked otoacoustic emissions. In this work, the optimization of these techniques and the interpretation of the experimental result are discussed. Time-frequency analysis of click-evoked otoacoustic emissions of 42 normal-hearing young subjects has been performed, using both wavelet and matching pursuit algorithms. Wavelet techniques are very effective to provide fast and reliable evaluation of the average latency of large samples of subjects. A major advantage of the matching pursuit technique, as observed by Jedrzejczak et al. [J. Acoust. Soc. Am. 115, 2148-2158 (2004)], is to provide detailed information about the time evolution of the response of single ears at selected frequencies. A hybrid matching pursuit algorithm that includes Fourier spectral information was developed, capable of speeding-up computation times and of identifying "spurious" atoms, whose latency-frequency relation is apparently anomalous. These atoms could be associated with several known phenomena, either intrinsic, such as intermodulation distortion, spontaneous emissions and multiple internal reflections, or extrinsic, such as instrumental noise, linear ringing and the acquisition window onset. A correct interpretation of these phenomena is important to get accurate estimates of the otoacoustic emission latency.

The synthesis of 9 alpha,11 alpha-epoxy-5 alpha-cholest-7-ene-3 beta,5,6 beta-triol (1), a highly oxygenated marine sterol containing a 9,11-epoxide moiety in the nucleus, is described. Epoxy sterol 1 was synthesized from cholesta-5,7-dien-3 beta-ol. Oxidation of this sterol with m-chloroperbenzoic acid followed by hydrolysis and acetylation furnished 5 alpha-cholest-7-ene-3 beta,5,6 alpha-triol 3,6-diacetate (2). Mercuric acetate dehydrogenation of diacetate 2, followed by oxidation with manganese dioxide and epoxidation with m-chloroper-benzoic acid, afforded 9 alpha,11 alpha-epoxy-3 beta,5-dihydroxy-5 alpha-cholest-7-en-6-one (5). Reduction of 5 with lithium aluminum hydride gave the desired compound 1. The structures of all synthetic intermediates were confirmed by 1H and 13C nuclear magnetic resonance (NMR) spectroscopy. A reassignment of resonances for carbons 1, 8, and 15 in the 13C NMR spectrum of 1, based on 2D-NMR correlation spectroscopy, has been accomplished.