The population dynamics of a canonical cognitive circuit Supplementary Information, bioRxiv, 2019-01-10
The brain constructs distributed representations of key low-dimensional variables. These variables may be external stimuli or internal constructs of quantities relevant for survival, such as a sense of one's location in the world. We consider that the high-dimensional population-level activity vectors are the fundamental representational currency of a neural circuit, and these vectors trace out a low-dimensional manifold whose dimension and topology matches those of the represented variable. This manifold perspective -- applied to the mammalian head direction circuit across rich waking behaviors and sleep -- enables powerful inferences about circuit representation and mechanism, including Direct visualization and blind discovery that the network represents a one-dimensional circular variable across waking and REM sleep; fully unsupervised decoding of the coded variable; stability and attractor dynamics in the representation; the discovery of new dynamical trajectories during sleep; the limiting role of external rather than internal noise in the fidelity of memory states; and the conclusion that the circuit is set up to integrate velocity inputs according to classical continuous attractor models.
biorxiv neuroscience 0-100-users 2019False-positive neuroimaging Undisclosed flexibility in testing spatial hypotheses allows presenting anything as a replicated finding, bioRxiv, 2019-01-09
AbstractHypothesis testing in neuroimaging studies relies heavily on treating named anatomical regions (e.g., “the amygdala”) as unitary entities. Though data collection and analyses are conducted at the voxel level, inferences are often based on anatomical regions. The discrepancy between the unit of analysis and the unit of inference leads to ambiguity and flexibility in analyses that can create a false sense of reproducibility. For example, hypothesizing effects on “amygdala activity” does not provide a falsifiable and reproducible definition of precisely which voxels or which patterns of activation should be observed. Rather, it comprises a large number of unspecified sub-hypotheses, leaving room for flexible interpretation of findings, which we refer to as “model degrees of freedom.” From a survey of 135 functional Magnetic Resonance Imaging studies in which researchers claimed replications of previous findings, we found that 42.2% of the studies did not report any quantitative evidence for replication such as activation peaks. Only 14.1% of the papers used exact coordinate-based or a priori pattern-based models. Of the studies that reported peak information, 42.9% of the ‘replicated’ findings had peak coordinates more than 15 mm away from the ‘original’ findings, suggesting that different brain locations were activated, even when studies claimed to replicate prior results. To reduce the flexible and qualitative region-level tests in neuroimaging studies, we recommend adopting quantitative spatial models and tests to assess the spatial reproducibility of findings. Techniques reviewed here include permutation tests on peak distance, Bayesian MANOVA, and a priori multivariate pattern-based models. These practices will help researchers to establish precise and falsifiable spatial hypotheses, promoting a cumulative science of neuroimaging.
biorxiv neuroscience 200-500-users 2019Optical clearing of living brains with MAGICAL to extend in vivo imaging, bioRxiv, 2019-01-09
To understand brain functions, it is important to observe directly how multiple neural circuits are performing in living brains. However, due to tissue opaqueness, observable depth and spatiotemporal resolution are severely degraded in vivo. Here, we propose an optical brain clearing method for in vivo fluorescence microscopy, termed MAGICAL (Magical Additive Glycerol Improves Clear Alive Luminance). MAGICAL enabled two-photon microscopy to capture vivid images with fast speed, at cortical layer V and hippocampal CA1 in vivo. Moreover, MAGICAL promoted conventional confocal microscopy to visualize finer neuronal structures including synaptic boutons and spines in unprecedented deep regions, without intensive illumination leading to phototoxic effects. Fluorescence Emission Spectrum Transmissive Analysis (FESTA) showed that MAGICAL improved in vivo transmittance of shorter wavelength light, which is vulnerable to optical scattering thus unsuited for in vivo microscopy. These results suggest that MAGICAL would transparentize living brains via scattering reduction.
biorxiv neuroscience 200-500-users 2019Associations 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 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 2019