Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.07.191031v1?rss=1

Authors: Quiroga-Martinez, D. R., Tillmann, B., Brattico, E., Cholvy, F., Fornoni, L., Vuust, P., Caclin, A.

Abstract:

In typical listeners, the perceptual salience of a surprising auditory event depends on the uncertainty of its context. For example, in melodies, pitch deviants are more easily detected and generate larger neural responses when the context is highly predictable than when it is less so. However, it is not known whether amusic listeners with abnormal pitch processing are sensitive to the degree of uncertainty of pitch sequences and, if so, whether they are to a different extent than typical listeners. To answer this question, we manipulated the uncertainty of short melodies while participants with and without congenital amusia underwent EEG recordings in a passive listening task. Uncertainty was manipulated by presenting melodies with different levels of complexity and familiarity, under the assumption that simpler and more familiar patterns would enhance pitch predictability. We recorded mismatch negativity (MMN) responses to pitch, intensity, timbre, location, and rhythm deviants as a measure of auditory surprise. We found reduced MMN amplitudes and longer peak latencies for all sound features with increasing levels of complexity, and putative familiarity effects only for intensity deviants. No significant group-by-complexity or group-by-familiarity interactions were detected. However, in amusics, pitch MMN responses peaked later and were disrupted in high complexity and unfamiliar melodies. Our results indicate that amusics are sensitive to the uncertainty of melodic sequences and hint at pitch-specific impairments in this population when uncertainty is high. As previous research has linked amusia with abnormal frontotemporal connectivity, our findings potentially suggest that processing pitch under high uncertainty conditions requires an intact frontotemporal loop.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.07.191239v1?rss=1

Authors: Book, G. A., Meda, S. A., Janssen, R., Dager, A. D., Poppe, A., Stevens, M. C., Assaf, M., Glahn, D., Pearlson, G. D.

Abstract:

We present an exploratory cross-sectional analysis of the effect of season and weather on Freesurfer-derived brain volumes from a sample of 3,279 healthy individuals collected on two MRI scanners in Hartford, CT, USA over a 15 year period. Weather and seasonal effects were analyzed using a single linear regression model with age, sex, motion, scan sequence, time-of-day, month of the year, and the deviation from average barometric pressure, air temperature, and humidity, as covariates. FDR correction for multiple comparisons was applied to groups of non-overlapping ROIs. Significant negative relationships were found between the left- and right- cerebellum cortex and pressure (t = -2.25, p = 0.049; t = -2.771, p = 0.017). Significant positive relationships were found between left- and right- cerebellum cortex and white matter between the comparisons of January/June and January/September. Significant negative relationships were found between several subcortical ROIs for the summer months compared to January. An opposing effect was observed between the supra- and infra-tentorium, with opposite effect directions in winter and summer. Cohens d effect sizes from monthly comparisons were similar to those reported in recent psychiatric big-data publications, raising the possibility that seasonal changes and weather may be confounds in large cohort studies. Additionally, changes in brain volume due to natural environmental variation have not been reported before and may have implications for weather-related and seasonal ailments.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.07.191262v1?rss=1

Authors: Weightman Potter, P. G., Washer, S., Jeffries, A. R., Holley, J. E., Gutowski, N. J., Dempster, E. L., Beall, C.

Abstract:

Aims/hypothesis: Recurrent hypoglycaemia (RH) is a major side-effect of intensive insulin therapy for people with diabetes. Changes in hypoglycaemia sensing by the brain contribute to the development of impaired counterregulatory responses to and awareness of hypoglycaemia. Little is known about the intrinsic changes in human astrocytes in response to acute and recurrent low glucose (RLG) exposure. Methods: Human primary astrocytes (HPA) were exposed to zero, one, three or four bouts of low glucose (0.1 mmol/l) for three hours per day for four days to mimic RH. On the fourth day, DNA and RNA were collected. Differential gene expression and ontology analyses were performed using DESeq2 and GOseq respectively. DNA methylation was assessed using the Infinium MethylationEPIC BeadChip platform. Results: 24 differentially expressed genes (DEGs) were detected (after correction for multiple comparisons). One bout of low glucose exposure had the largest effect on gene expression. Pathway analyses revealed that endoplasmic-reticulum (ER) stress-related genes such as HSPA5, XBP1, and MANF, involved in the unfolded protein response (UPR), were all significantly increased following LG exposure, which was diminished following RLG. There was little correlation between differentially methylated positions and changes in gene expression yet the number of bouts of LG exposure produced distinct methylation signatures. Conclusions/interpretation: These data suggest that exposure of human astrocytes to transient LG triggers activation of genes involved in the UPR linked to endoplasmic reticulum (ER) stress. Following RLG, the activation of UPR related genes was diminished, suggesting attenuated ER stress. This may be mediated by metabolic adaptations to better preserve intracellular and/or ER ATP levels, but this requires further investigation.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.07.191767v1?rss=1

Authors: Bugain, M., Dimech, Y., Torzhenskaya, N., Thiebaut de Schotten, M., Caspers, S., Muscat, R., Bajada, C. J.

Abstract:

The continuously developing field of magnetic resonance imaging (MRI) has made a considerable contribution to the knowledge of brain architecture. It has given shape to a desire to construct a complete map of functional and structural connections. In particular, diffusion MRI paired with tractography has facilitated a non-invasive exploration of structural brain anatomy, which has helped build evidence for the existence of many association, projection and commissural fiber tracts. However, there is still a scarcity in research studies related to intralobar association fibers. The Dejerines' (two of the most notable neurologists of 19th century France) gave an in-depth description of the intralobar fibers of the occipital lobe. Unfortunately, their exquisite work has since been sparsely referred to in the modern literature. This work gives the first modern description of many of the occipital intralobar lobe fibers described by the Dejerines. We perform a virtual dissection and reconstruct the tracts using diffusion MRI tractography. The virtual dissection is guided by the Dejerines' treatise, Anatomie des Centres Nerveux. As an accompaniment to this article, the authors provided a French-to-English translation of the treatise portion concerning intra-occipital fiber bundles. This text provides the original description of five intralober occipital tracts, namely: the stratum calcarinum, the stratum proprium cunei, the vertical occipital fasciculus of Wernicke, the transverse fasciculus of the cuneus (TFC) and the transverse fasciculus of the lingual lobe of Vialet. It was possible to reconstruct all these tracts except for the TFC - possibly because its trajectory intermingles with a large amount of other fiber bundles. For completeness, the recently described sledge runner fasciculus, although not one of the Dejerine tracts, was identified and successfully reconstructed.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.07.191809v1?rss=1

Authors: Dadar, M., Potvin, O., Camicioli, R., Duchesne, S.

Abstract:

Introduction: Volumetric estimates of subcortical and cortical structures, extracted from T1-weighted MRIs, are widely used in many clinical and research applications. Here, we investigate the impact of the presence of white matter hyperintensities (WMHs) on FreeSurfer grey matter (GM) structure volumes and its possible bias on functional relationships. Methods: T1-weighted images from 1077 participants (4321 timepoints) from the Alzheimer's Disease Neuroimaging Initiative were processed with FreeSurfer version 6.0.0. WMHs were segmented using a previously validated algorithm on either T2-weighted or Fluid-attenuated inversion recovery (FLAIR) images. Mixed effects models were used to assess the relationships between overlapping WMHs and GM structure volumes and overal WMH burden, as well as to investigate whether such overlaps impact associations with age, diagnosis, and cognitive performance. Results: Participants with higher WMH volumes had higher overalps with GM volumes of bilateral caudate, cerebral cortex, putamen, thalamus, pallidum, and accumbens areas (P < 0.0001). When not corrected for WMHs, caudate volumes increased with age (P < 0.0001) and were not different between cognitively healthy individuals and age-matched probable Alzheimers disease patients. After correcting for WMHs, caudate volumes decreased with age (P < 0.0001), and Alzheimers disease patients had lower caudate volumes than cognitively healthy individuals (P < 0.01). Uncorrected caudate volume was not associated with ADAS13 scores, whereas corrected lower caudate volumes were significantly associated with poorer cognitive performance (P < 0.0001). Conclusions: Presence of WMHs leads to systematic inaccuracies in GM segmentations, particularly for the caudate, which can also change clinical associations. While specifically measured for the Freesurfer toolkit, this problem likely affects other algorithms.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.06.190553v1?rss=1

Authors: Davis, G. L., Minerva, A. R., Lario, A., Rodriguez, C. I., Gunaydin, L. A.

Abstract:

Obsessive-Compulsive Disorder (OCD), characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions), is associated with dysfunction in fronto-striatal circuits. There are currently no fast-acting pharmacological treatments for OCD. However, recent clinical studies demonstrated that an intravenous infusion of ketamine rapidly reduces OCD symptoms. To probe mechanisms underlying ketamine's therapeutic effect on OCD-like behaviors, we used the SAPAP3 knockout (KO) mouse model of compulsive grooming. Here we recapitulate the fast-acting therapeutic effect of ketamine on compulsive behavior, and show that ketamine increases activity of dorsomedial prefrontal neurons projecting to the dorsomedial striatum in KO mice. Optogenetically mimicking this increase in fronto-striatal activity rescued compulsive grooming behavior in KO mice. Conversely, inhibiting this circuit in wild-type mice increased grooming. These studies demonstrate that ketamine increases activity in a fronto-striatal circuit that causally controls compulsive grooming behavior, suggesting this circuit may be important for ketamine's therapeutic effects in OCD.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.06.187187v1?rss=1

Authors: Kobelt, M., Sommer, V. R., Keresztes, A., Werkle-Bergner, M., Sander, M. C.

Abstract:

The distinctiveness of neural information representation is crucial for successful memory performance but declines with advancing age. Computational models implicate age-related neural dedifferentiation on the level of item representations, but previous studies mostly focused on age differences of categorical information representation in higher-order visual regions. In an age-comparative fMRI study, we combined univariate analyses and whole-brain searchlight pattern similarity analyses to elucidate age differences in neural distinctiveness at both category and item levels and their relation to memory. Age-related neural dedifferentiation was shown as reduced category-selective processing in ventral visual cortex and impoverished item specificity in occipital regions. Importantly, successful subsequent memory performance built upon high item stability which was greater in younger than older adults. Finally, we identified a multivariate profile of neural distinctiveness across representational levels that captured both age group and recognition performance differences, emphasizing that neural dedifferentiation is a generalized phenomenon in the aging brain.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.06.184473v1?rss=1

Authors: Dorfschmidt, L., Bethlehem, R. A. I., Seidlitz, J., Vasa, F., White, S. R., Romero-Garcia, R., Kitzbichler, M. G., Aruldass, A., Goodyer, I. M., Fonagy, P., Jones, P. B., Dolan, R. J., the NSPN Consortium,, Harrison, N. A., Vertes, P. E., Bullmore, E. T.

Abstract:

Adolescence is a period of critical development of the brain, that coincides with a sexually dimorphic increase in risk of depression for females. We hypothesized that there might be sexual dimorphisms in human brain network development underlying the dimorphism in depression. First, we tested for sex differences in parameters of brain network development (baseline connectivity at age 14, FC14, adolescent change in connectivity FC14-26 and maturational index, MI), measured in repeated resting state functional MRI scans from N=298 healthy young people aged 14-26 years, scanned a total of 520 times. We measured the maturational index (-1

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.05.188847v1?rss=1

Authors: Chen, X., Zhou, M., Gong, Z., Xu, W., Liu, X., Huang, T., Zhen, Z., Liu, J.

Abstract:

Deep neural networks (DNNs) have attained human-level performance on dozens of challenging tasks through an end-to-end deep learning strategy. Deep learning gives rise to data representations with multiple levels of abstraction; however, it does not explicitly provide any insights into the internal operations of DNNs. Its success appeals to neuroscientists not only to apply DNNs to model biological neural systems, but also to adopt concepts and methods from cognitive neuroscience to understand the internal representations of DNNs. Although general deep learning frameworks such as PyTorch and TensorFlow could be used to allow such cross-disciplinary studies, the use of these frameworks typically requires high-level programming expertise and comprehensive mathematical knowledge. A toolbox specifically designed for cognitive neuroscientists to map DNNs and brains is urgently needed. Here, we present DNNBrain, a Python-based toolbox designed for exploring internal representations in both DNNs and the brain. By integrating DNN software packages and well-established brain imaging tools, DNNBrain provides application programming and command line interfaces for a variety of research scenarios, such as extracting DNN activation, probing DNN representations, mapping DNN representations onto the brain, and visualizing DNN representations. We expect that our toolbox will accelerate scientific research in applying DNNs to model biological neural systems and utilizing paradigms of cognitive neuroscience to unveil the black box of DNNs.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.05.188565v1?rss=1

Authors: Schmid, F., Conti, G., Jenny, P., Weber, B.

Abstract:

Cortical microinfarcts are caused by blood flow disturbances and are linked to pathologies like cerebral amyloid angiopathy and dementia. Despite their relevance for disease progression, microinfarcts often remain undetected and the smallest scale of disturbance has not yet been identified. We employ blood flow simulations in realistic microvascular networks from the mouse cortex to quantify the impact of single capillary occlusions. We reveal that the severity of a microstroke is strongly affected by the local vascular topology and the baseline flow rate in the occluded capillary. The largest changes in flow rate are observed in capillaries with two in- and two outflows. Interestingly, this specific topological configuration only occurs with a frequency of 8%, while the majority of capillaries are likely designed to efficiently supply oxygen and nutrients. Taken together, microstrokes likely induce a cascade of local disturbances in the surrounding tissue, which might accumulate and impair energy supply locally.

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