PaperPlayer biorxiv neuroscience

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.11.21.391458v1?rss=1

Authors: Cataldo, A., Hagura, N., Hyder, Y., Haggard, P.

Abstract:

Human perception of touch is mediated by inputs from multiple channels. Classical theories postulate independent contributions of each channel to each tactile feature, with little or no interaction between channels. In contrast to this view, we show that inputs from two sub-modalities of mechanical input channels interact to determine tactile perception. The flutter-range vibration channel was activated anomalously using hydroxy--sanshool, a bioactive compound of Szechuan pepper, which chemically induces tingling sensations. We tested whether this tingling sensation on the lips was modulated by sustained mechanical pressure. Across four experiments, we show that sustained touch inhibits sanshool tingling sensations in a location-specific, pressure-level and time-dependent manner. Additional experiments ruled out mediation of nociceptive or affective (C-tactile) channels underlying this interaction. These results reveal novel inhibitory influence from steady-pressure onto flutter-range tactile perceptual channels, consistent with early-stage interactions between mechanoreceptor inputs within the somatosensory pathway.

Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.11.20.391482v1?rss=1

Authors: Lopez-Gonzalez, A., Panda, R., Ponce-Alvarez, A., Zamora, G., Escrichs, A., Martial, C., Thibaut, A., Gosseries, O., Kringelbach, M. L., Annen, J., Laureys, S., Deco, G.

Abstract:

Low-level states of consciousness are characterised by disruptions of brain dynamics that sustain arousal and awareness. Yet, how structural, dynamical, local and network brain properties interplay in the different levels of consciousness is unknown. Here, we studied the fMRI brain dynamics from patients that suffered brain injuries leading to a disorder of consciousness and from subjects undergoing propofol-induced anaesthesia. We showed that pathological and pharmacological low-level states of consciousness displayed less recurrent, less diverse, less connected, and more segregated synchronization patterns than conscious states. We interpreted these effects using whole-brain models built on healthy and injured connectomes. We showed that altered dynamics arise from a global reduction of network interactions, together with more homogeneous and more structurally constrained local dynamics. These effects were accentuated using injured connectomes. Notably, these changes lead the hub regions to lose their stability during low-level states of consciousness, thus attenuating the core-periphery structure of brain dynamics.

Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.11.22.393397v1?rss=1

Authors: Magri, C., Konkle, T., Caramazza, A.

Abstract:

In human occipitotemporal cortex, brain responses to depicted inanimate objects have a large-scale organization by real-world object size. Critically, the size of objects in the world is systematically related to behaviorally-relevant properties: small objects are often grasped and manipulated (e.g., forks), while large objects tend to be less motor-relevant (e.g., tables), though this relationship does not always have to be true (e.g., picture frames and wheelbarrows). To determine how these two dimensions interact, we measured brain activity with functional magnetic resonance imaging while participants viewed a stimulus set of small and large objects with either low or high motor-relevance. The results revealed that the size organization was evident for objects with both low and high motor-relevance; further, a motor-relevance map was also evident across both large and small objects. Targeted contrasts revealed that typical combinations (small motor-relevant vs. large non-motor-relevant) yielded more robust topographies than the atypical covariance contrast (small non-motor-relevant vs. large motor-relevant). In subsequent exploratory analyses, a factor analysis revealed that the construct of motor-relevance was better explained by two underlying factors: one more related to manipulability, and the other to whether an object moves or is stable. The factor related to manipulability better explained responses in lateral small-object preferring regions, while the factor related to object stability (lack of movement) better explained responses in ventromedial large-object preferring regions. Taken together, these results reveal that the structure of neural responses to objects of different sizes further reflect behavior-relevant properties of manipulability and stability, and contribute to a deeper understanding of some of the factors that help the large-scale organization of object representation in high-level visual cortex.

Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.11.20.392308v1?rss=1

Authors: Ohata, R., Asai, T., Imaizumi, S., Imamizu, H.

Abstract:

The subjective experience of causing an action is known as the sense of agency. Dysfunction in the sense of agency has been suggested as a cause of auditory hallucinations (AHs), an important diagnostic criterion for schizophrenia. However, agency over speech has not been extensively characterized in previous empirical studies. Here, we examine both implicit and explicit measures of the sense of agency and reveal bottom-up and top-down components that constitute self-agency during speech. The first is action-outcome causality, which is perceived based on a low-level sensorimotor process when hearing their own voice following their speech. The second component is self-voice identity, which is embedded in the acoustic quality of voice and dominantly influences agency over speech at the cognitive judgment level. Our findings provide profound insight into the sense of agency over speech and present an informative perspective for understanding aberrant experience in AHs.

Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.11.20.392001v1?rss=1

Authors: Györi, J., Kohn, A. B., Romanova, D., Moroz, L. L.

Abstract:

ATP and its ionotropic P2X receptors are components of the most ancient signaling systems. However, little is known about the distribution and function of purinergic transmission in invertebrates. Here, we cloned, expressed, and pharmacologically characterized P2X receptors in the sea slug Aplysia californica - the prominent model in cellular and system neuroscience. These P2X receptors were successfully expressed in Xenopus oocytes and displayed activation by ATP (EC50=306 M) with two-phased kinetics as well as Na+-dependence. The ATP analog, Bz-ATP, was a less effective agonist (~20%) than ATP, and PPADS was a more potent inhibitor of the P2X receptors than the suramin. We showed that P2X receptors are uniquely expressed within Aplysia's cerebral bioenergetic center (F-cluster). Using RNA-seq, we found that the F-cluster contains more than a dozen unique secretory peptides, including three insulins, interleukins, and potential toxins, as well as ecdysone-type receptors and a district subset of ion channels. This structure is one of the most prominent integrative centers in the entire CNS and remarkably different from the morphologically similar neurosecretory center (bag-cluster) involved in egg-laying behavior. Using RNA-seq, we also characterized the expression of P2X receptors across more than a dozen Aplysia peripheral tissues and developmental stages. We showed that P2X receptors are predominantly expressed in chemosensory structures and during early cleavage stages. The localization and pharmacology of P2X receptors in Aplysia highlight the evolutionary conservation of bioenergetic sensors and chemosensory purinergic transmission across animals. This study also provides a foundation to decipher homeostatic mechanisms in development and neuroendocrine systems.

Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.11.20.390955v1?rss=1

Authors: Minino, R., Troisi Lopez, E., Sorrentino, P., Rucco, R., Lardone, A., Pesoli, M., Tafuri, D., Mandolesi, L., Sorrentino, G., Liparoti, M.

Abstract:

The use of rhythmic acoustic stimulation (RAS) in improving gait and balance in healthy elderly subjects has been widely investigated. However, methodologies and results are often controversial. In this study, we hypothesize that both the kinematic features of gait and stability, depend on the frequency at which RAS is administered. Our aim was to observe, through 3D Gait Analysis, the effect of different types of RAS (at a fixed frequency or based on the average cadence of each subject) on both gait spatio-temporal parameters and stability. The latter was estimated through an innovative measure, the trunk displacement index (TDI) that we have recently implemented. We observed that the low frequencies RAS led to a general slowdown of gait, which did not provide any clear benefit and produced harmful effects on stability when the frequency became too low compared to the individual natural frequency. On the contrary, the high frequencies of RAS showed a slight acceleration of gait, accompanied by better stability (as documented by a lower TDI value), regardless of the type of RAS. Finally, the RAS equal to the individual natural cadence also produced an increase in stability.

Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.11.20.390120v1?rss=1

Authors: Cetin-Karayumak, S., Stegmayer, K., Walther, S., Szeszko, P. R., Crow, T., James, A., Keshavan, M., Kubicki, M., Rathi, Y.

Abstract:

The findings from diffusion-weighted magnetic resonance imaging (dMRI) studies often show inconsistent and sometimes contradictory results due to small sample sizes as well as differences in acquisition parameters and pre-/post-processing methods. To address these challenges, collaborative multi-site initiatives have provided an opportunity to collect larger and more diverse groups of subjects, including those with neuropsychiatric disorders, leading to increased power and findings that may be more representative at the group and individual level. With the availability of these datasets openly, the ability of joint analysis of multi-site dMRI data has become more important than ever. However, intrinsic- or acquisition-related variability in scanner models, acquisition protocols, and reconstruction settings hinder pooling multi-site dMRI directly. One powerful and fast statistical harmonization method called ComBat (https://github.com/Jfortin1/ComBatHarmonization) was developed to mitigate the "batch effect" in gene expression microarray data and was adapted for multi-site dMRI harmonization to reduce scanner/site effect. Our goal is to evaluate this commonly used harmonization approach using a large diffusion MRI dataset involving 542 individuals from 5 sites. We investigated two important aspects of using ComBat for harmonization of fractional anisotropy (FA) across sites: First, we assessed how well ComBat preserves the inter-subject biological variability (measured by the effect sizes of between-group FA differences) after harmonization. Second, we evaluated the effect of minor differences in pre-processing on ComBat's performance. While the majority of effect sizes are mostly preserved in some sites after harmonization, they are not well-preserved at other sites where non-linear scanner contributions exist. Further, even minor differences in pre-processing can yield unwanted effects during ComBat harmonization. Thus, our findings suggest paying careful attention to the data being harmonized as well as using the same processing pipeline while using ComBat for data harmonization.

Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.11.20.392175v1?rss=1

Authors: Tokarew, J. M., El Kodsi, D. N., Lengacher, N. A., Fehr, T. K., Nguyen, A. P., Shutinoski, B., O'Nuallain, B., Jin, M., Khan, J., Ng, A. C. H., Li, J., Jiang, Q., Zhang, M., Wang, L., Sengupta, R., Barber, K., Tran, A., Zandee, S., Dong, X., Scherzer, C. R., Prat, A., Tsai, E., Takanashi, M., Hattori, N., Chan, J. A., Zecca, L., West, A., Holmgren, A., Puente, L., Shaw, G. S., Toth, G., Woulfe, J., Taylor, P., Tomlinson, J. J., Schlossmacher, M. G.

Abstract:

The mechanisms by which parkin protects the adult human brain from Parkinson disease remain incompletely understood. We hypothesized that parkin cysteines participate in redox reactions, which are reflected in its posttranslational modifications. We found that in human control brain, including the S. nigra, parkin is largely insoluble after age 40 years, which is linked to its oxidation, e.g., at Cys95 and Cys253. In mice, oxidative stress increases posttranslational modifications at parkin cysteines and reduces its solubility. Oxidation of recombinant parkin also promotes insolubility and aggregate formation, but in parallel, lowers hydrogen peroxide (H2O2). This thiol-based redox activity is diminished by parkin point mutants, e.g., p.C431F and p.G328E. Intriguingly, in parkin-deficient human brain H2O2 concentrations are elevated. In prkn-null mice, H2O2 levels are dysregulated under oxidative stress conditions, such as acutely by MPTP-toxin exposure or chronically due to a second genetic hit. In dopamine toxicity studies, wild-type parkin, but not disease-linked mutants, protects human dopaminergic M17 cells, in part through lowering H2O2. Parkin also neutralizes reactive, electrophilic dopamine metabolites via adduct formation, which occurs foremost at primate-specific Cys95. Further, wild-type but not p.C95A-mutant parkin augments melanin formation. In sections of normal, adult human midbrain, parkin specifically co-localizes with neuromelanin pigment, frequently within LAMP-3/CD63+ lysosomes. We conclude that oxidative modifications of parkin cysteines are associated with protective outcomes, which include the reduction of H2O2, conjugation of reactive dopamine metabolites, sequestration of radicals within insoluble aggregates, and increased melanin formation. The loss of these redox effects may augment oxidative stress in dopamine producing neurons of mutant PRKN allele carriers, thereby contributing to neurodegeneration.

Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.11.20.391805v1?rss=1

Authors: Wall, M. B., Freeman, T. P., Hindocha, C., Demetriou, L., Ertl, N., Freeman, A. M., Jones, A. P. M., Lawn, W., Pope, R., Mokrysz, C., Solomons, D., Statton, B., Walker, H. R., Yamamori, Y., Yang, Z., Yim, J. L. L., Nutt, D. J., Howes, O. D., Curran, H. V., Bloomfield, M.

Abstract:

Cannabidiol (CBD) and {Delta}9-tetrahydrocannabinol (THC) are two major constituents of cannabis with contrasting mechanisms of action. THC is the major psychoactive, addiction-promoting, and psychotomimetic compound, while CBD may have somewhat opposite effects. The brain effects of these drugs alone and in combination are poorly understood. In particular the striatum is implicated in the pathophysiology of several psychiatric disorders, but it is unclear how THC and CBD influence striato-cortical connectivity. Across two placebo-controlled, double-blind studies, we examine the effects of THC, CBD, and THC+CBD on the functional connectivity of striatal sub-divisions (associative, limbic, and sensorimotor) using resting-state functional Magnetic Resonance Imaging (fMRI) and seed-based functional connectivity analyses. Study 1 (N=17; inhaled 8mg THC, 8mg THC+10mg CBD, placebo) showed strong disruptive effects of both THC and THC+CBD conditions on connectivity in the associative and sensorimotor networks, but a specific effect of THC in the limbic striatum, which was alleviated in the THC+CBD condition such that it did not differ from placebo. In Study 2 (N=23, oral 600mg CBD, placebo) CBD increased connectivity in the associative network, but relatively minor decreases/disruptions were found in the limbic and sensorimotor. In conclusion, THC strongly disrupts striato-cortical networks, and this effect is selectively mitigated in the limbic striatum when co-administered with CBD. When administered alone, 600mg oral CBD has a more complex effect profile of relative increases and decreases in connectivity. The insula emerges as a key region affected by cannabinoid-induced changes in functional connectivity, with potential implications for understanding cannabis related disorders, and the development of cannabinoid therapeutics.

Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.11.17.387043v1?rss=1

Authors: Kalidindi, H. T., Cross, K. P., Lillicrap, T. P., Omrani, M., Falotico, E., Sabes, P. N., Scott, S. H.

Abstract:

Recent studies hypothesize that motor cortical (MC) dynamics are generated largely through its recurrent connections based on observations that MC activity exhibits rotational structure. However, behavioural and neurophysiological studies suggest that MC behaves like a feedback controller where continuous sensory feedback and interactions with other brain areas contribute substantially to MC processing. We investigated these apparently conflicting theories by building recurrent neural networks that controlled a model arm and received sensory feedback about the limb. Networks were trained to counteract perturbations to the limb and to reach towards spatial targets. Network activities and sensory feedback signals to the network exhibited rotational structure even when the recurrent connections were removed. Furthermore, neural recordings in monkeys performing similar tasks also exhibited rotational structure not only in MC but also in somatosensory cortex. Our results argue that rotational structure may reflect dynamics throughout voluntary motor circuits involved in online control of motor actions.

Copy rights belong to original authors. Visit the link for more info