Associations between vascular risk factors and brain MRI indices in UK Biobank Supplementary Material, bioRxiv, 2019-01-04
Aims Several factors are known to increase risk for cerebrovascular disease and dementia, but there is limited evidence on associations between multiple vascular risk factors (VRFs) and detailed aspects of brain macro- and microstructure in large community-dwelling populations across middle- and older age. Methods and Results Associations between VRFs (smoking, hypertension, pulse pressure, diabetes, hypercholersterolaemia, BMI, and waist-hip ratio) and both global and regional brain structural and diffusion MRI markers were examined in UK Biobank (N = 9722, age range 44-77 years). A larger number of VRFs was associated with greater brain atrophy, lower grey matter volume, and poorer white matter health. Effect sizes were small (brain structural R2 ≤ 1.8%). Higher aggregate vascular risk was related to multiple regional MRI hallmarks associated with dementia risk lower frontal and temporal cortical volumes, lower subcortical volumes, higher white matter hyperintensity volumes, and poorer white matter microstructure in association and thalamic pathways. Smoking pack years, hypertension and diabetes showed the most consistent associations across all brain measures. Hypercholesterolaemia was not uniquely associated with any MRI marker. Conclusion Higher levels of VRFs were associated with poorer brain health across grey and white matter macro- and microstructure. Effects are mainly additive, converging upon frontal and temporal cortex, subcortical structures, and specific classes of white matter fibres. Though effect sizes were small, these results emphasise the vulnerability of brain health to vascular factors even in relatively healthy middle and older age, and the potential to partly ameliorate cognitive decline by addressing these malleable risk factors.
biorxiv neuroscience 0-100-users 2019Recording of sonic attacks on U.S. diplomats in Cuba spectrally matches the echoing call of a Caribbean cricket, bioRxiv, 2019-01-04
Beginning in late 2016, diplomats posted to the United States embassy in Cuba began to experience unexplained health problems including ear pain, tinnitus, vertigo, and cognitive difficulties which reportedly began after they heard strange noises in their homes or hotel rooms. In response, the U.S. government dramatically reduced the number of diplomats posted at the U.S. embassy in Havana. U.S. officials initially believed a sonic attack might be responsible for their ailments. The sound linked to these attacks, which has been described as a high-pitched beam of sound, was recorded by U.S. personnel in Cuba and released by the Associated Press (AP). Because these recordings are the only available non-medical evidence of the sonic attacks, much attention has focused on identifying health problems and the origin of the acoustic signal. As shown here, the calling song of the Indies short-tailed cricket (Anurogryllus celerinictus) matches, in nuanced detail, the AP recording in duration, pulse repetition rate, power spectrum, pulse rate stability, and oscillations per pulse. The AP recording also exhibits frequency decay in individual pulses, a distinct acoustic signature of cricket sound production. While the temporal pulse structure in the recording is unlike any natural insect source, when the cricket call is played on a loudspeaker and recorded indoors, the interaction of reflected sound pulses yields a sound virtually indistinguishable from the AP sample. This provides strong evidence that an echoing cricket call, rather than a sonic attack or other technological device, is responsible for the sound in the released recording. Although the causes of the health problems reported by embassy personnel are beyond the scope of this paper, our findings highlight the need for more rigorous research into the source of these ailments, including the potential psychogenic effects, as well as possible physiological explanations unrelated to sonic attacks.
biorxiv biophysics 200-500-users 2019Enjoy The Violence Is appreciation for extreme music the result of cognitive control over the threat response system?, bioRxiv, 2019-01-03
Traditional neurobiological theories of musical emotions explain well why extreme music such as punk, hardcore or metal, whose vocal and instrumental characteristics share much similarity with acoustic threat signals, should evoke unpleasant feelings for a large proportion of listeners. Why it doesn't for metal music fans, however, remains a theoretical challenge metal fans may differ from non-fans in how they process acoustic threat signals at the sub-cortical level, showing deactivated or reconditioned responses that differ from controls. Alternatively, it is also possible that appreciation for metal depends on the inhibition by cortical circuits of a normal low-order response to auditory threat. In a series of three experiments, we show here that, at a sensory level, metal fans actually react equally negatively, equally fast and even more accurately to cues of auditory threat in vocal and instrumental contexts than non-fans. Conversely, cognitive load somewhat appears to reduce fans' appreciation of metal to the level reported by non-fans. Taken together, these results are not compatible with the idea that extreme music lovers do so because of a different low-level response to threat, but rather, highlight a critical contribution of higher-order cognition to the aesthetic experience. These results are discussed in the light of recent higher-order theories of emotional consciousness, which we argue should be generalized to the emotional experience of music across musical genres.
biorxiv neuroscience 200-500-users 2019General visual and contingent thermal cues interact to elicit attraction in female Aedes aegypti mosquitoes, bioRxiv, 2019-01-03
Female Aedes aegypti mosquitoes use multiple sensory modalities to hunt human hosts to obtain a blood-meal for egg production. Attractive cues include carbon dioxide (CO2), a major component of exhaled breath [1, 2]; heat elevated above ambient temperature, signifying warm-blooded skin [3, 4]; and dark visual contrast [5, 6], proposed to bridge long-range olfactory and short-range thermal cues [7]. Any of these sensory cues in isolation is an incomplete signal of a human host, and so a mosquito must integrate multi-modal sensory information before committing to approaching and biting a person [8]. Here, we study the interaction of visual cues, heat, and CO2 to investigate the contributions of human-associated stimuli to host-seeking decisions. We show that tethered flying mosquitoes strongly orient toward dark visual contrast regardless of CO2 stimulation and internal host-seeking status. This suggests that attraction to visual contrast is general, and not contingent on other host cues. In free-flight experiments with CO2, adding a dark contrasting visual cue to a warmed surface enhanced host-seeking. Moderate warmth became more attractive to mosquitoes, and mosquitoes aggregated on the cue at all non-noxious temperatures. Gr3 mutants, unable to detect CO2, were lured to the visual cue at ambient temperatures, but fled and did not return when the surface was warmed to host-like temperatures. This suggests that attraction to thermal cues is contingent on the presence of the additional human sensory cue CO2. Our results illustrate that mosquitoes integrate general attractive visual stimuli with the context-dependent thermal stimuli to seek promising sites for blood-feeding.
biorxiv neuroscience 100-200-users 2019Highly Heritable and Functionally Relevant Breed Differences in Dog Behavior, bioRxiv, 2019-01-02
AbstractVariation across dog breeds presents a unique opportunity for investigating the evolution and biological basis of complex behavioral traits. We integrated behavioral data from more than 17,000 dogs from 101 breeds with breed-averaged genotypic data (N = 5,697 dogs) from over 100,000 loci in the dog genome. Across 14 traits, we found that breed differences in behavior are highly heritable, and that clustering of breeds based on behavior accurately recapitulates genetic relationships. We identify 131 single nucleotide polymorphisms associated with breed differences in behavior, which are found in genes that are highly expressed in the brain and enriched for neurobiological functions and developmental processes. Our results provide insight into the heritability and genetic architecture of complex behavioral traits, and suggest that dogs provide a powerful model for these questions.
biorxiv animal-behavior-and-cognition 200-500-users 2019Whole-genome sequencing of rare disease patients in a national healthcare system, bioRxiv, 2019-01-02
Most patients with hereditary rare diseases do not receive a molecular diagnosis and the aetiological variants and mediating genes for half such disorders remain to be discovered. We implemented whole-genome sequencing (WGS) in a national healthcare system to streamline diagnosis and to discover unknown aetiological variants, in the coding and non-coding regions of the genome. In a pilot study for the 100,000 Genomes Project, we generated WGS data for 13,037 participants, of whom 9,802 had a rare disease, and provided a genetic diagnosis to 1,040 of the 7,065 patients with detailed phenotypic data. We identified 99 Mendelian associations between genes and rare diseases, of which at least 80 are confirmed aetiological. Using WGS of UK Biobank, we showed that rare alleles can explain the presence of some individuals in the tails of a quantitative red blood cell (RBC) trait 1. Finally, we reported novel non-coding variants which cause disease through the disruption of transcription of ARPC1B, GATA1, LRBA and MPL. Our study demonstrates a synergy by using WGS for diagnosis and aetiological discovery in routine healthcare.
biorxiv genomics 200-500-users 2019