On November 16, 2021, Clarivate Analytics announced the list of “Highly Cited Researchers 2021”.
This week, we would like to share several latest articles from Clarivate Analytics “Highly Cited Researchers 2021” in Neuroscience and Behavior research fields.
Title: fMRI neurofeedback in the motor system elicits bidirectional changes in activity and in white matter structure in the adult human brain
Authors: Cassandra Sampaio-Baptista, Heather F. Neyedli, Zeena-Britt Sanders, Kata Diosi, David Havard, YunYing Huang, Jesper L. R. Andersson, Michael Lühr, Rainer Goebel, Heidi Johansen-Berg
Type: Report of Cell Reports
White matter (WM) plasticity supports skill learning and memory. Up- and downregulation of brain activity in animal models lead to WM alterations. But can bidirectional brain-activity manipulation change WM structure in the adult human brain? We employ fMRI neurofeedback to endogenously and directionally modulate activity in the sensorimotor cortices. Diffusion tensor imaging is acquired before and after two separate conditions, involving regulating sensorimotor activity either up or down using real or sham neurofeedback (n = 20 participants × 4 scans). We report rapid opposing changes in corpus callosum microstructure that depend on the direction of activity modulation. Our findings show that fMRI neurofeedback can be used to endogenously and directionally alter not only brain-activity patterns but also WM pathways connecting the targeted brain areas. The level of associated brain activity in connected areas is therefore a possible mediator of previously described learning-related changes in WM.
Access this article: https://doi.org/10.1016/j.celrep.2021.109890
Title: Identification of retinoblastoma binding protein 7 (Rbbp7) as a mediator against tau acetylation and subsequent neuronal loss in Alzheimer’s disease and related tauopathies
Authors: Nikhil Dave, Austin S. Vural, Ignazio S. Piras, Wendy Winslow, Likith Surendra, Joanna K. Winstone, Thomas G. Beach, Matthew J. Huentelman, Ramon Velazquez
Type: Original Paper of Acta Neuropathologica
Evidence indicates that tau hyper-phosphorylation and subsequent neurofibrillary tangle formation contribute to the extensive neuronal death in Alzheimer’s disease (AD) and related tauopathies. Recent work has identified that increased tau acetylation can promote tau phosphorylation. Tau acetylation occurs at lysine 280 resulting from increased expression of the lysine acetyltransferase p300. The exact upstream mechanisms mediating p300 expression remain elusive. Additional work highlights the role of the epigenome in tau pathogenesis, suggesting that dysregulation of epigenetic proteins may contribute to acetylation and hyper-phosphorylation of tau. Here, we identify and focus on the histone-binding subunit of the Nucleosome Remodeling and Deacetylase (NuRD) complex: Retinoblastoma-Binding Protein 7 (Rbbp7). Rbbp7 chaperones chromatin remodeling proteins to their nuclear histone substrates, including histone acetylases and deacetylases. Notably, Rbbp7 binds to p300, suggesting that it may play a role in modulating tau acetylation. We interrogated Rbbp7 in post-mortem brain tissue, cell lines and mouse models of AD. We found reduced Rbbp7 mRNA expression in AD cases, a significant negative correlation with CERAD (neuritic plaque density) and Braak Staging (pathogenic tau inclusions) and a significant positive correlation with post-mortem brain weight. We also found a neuron-specific downregulation of Rbbp7 mRNA in AD patients. Rbbp7 protein levels were significantly decreased in 3xTg-AD and PS19 mice compared to NonTg, but no decreases were found in APP/PS1 mice that lack tau pathology. In vitro, Rbbp7 overexpression rescued TauP301L-induced cytotoxicity in immortalized hippocampal cells and primary cortical neurons. In vivo, hippocampal Rbbp7 overexpression rescued neuronal death in the CA1 of PS19 mice. Mechanistically, we found that increased Rbbp7 reduced p300 levels, tau acetylation at lysine 280 and tau phosphorylation at AT8 and AT100 sites. Collectively, these data identify a novel role of Rbbp7, protecting against tau-related pathologies, and highlight its potential as a therapeutic target in AD and related tauopathies
Access this article: https://doi.org/10.1007/s00401-021-02323-1
Title: The detailed organization of the human cerebellum estimated by intrinsic functional connectivity within the individual
Authors: Aihuiping Xue, Ru Kong, Qing Yang, Mark C. Eldaief, Peter A. Angeli, Lauren M. DiNicola, Rodrigo M. Braga, Randy L. Buckner, B. T. Thomas Yeo
Type: Research Article of Journal of Neurophysiology
Distinct regions of the cerebellum connect to separate regions of the cerebral cortex forming a complex topography. Although cerebellar organization has been examined in group-averaged data, study of individuals provides an opportunity to discover features that emerge at a higher spatial resolution. Here, functional connectivity MRI was used to examine the cerebellum of two intensively sampled individuals (each scanned 31 times). Connectivity to somatomotor cortex showed the expected crossed laterality and topography of the body maps. A surprising discovery was connectivity to the primary visual cortex along the vermis with evidence for representation of the central field. Within the hemispheres, each individual displayed a hierarchical progression from the inverted anterior lobe somatomotor map through to higher-order association zones. The hierarchy ended at Crus I/II and then progressed in reverse order through to the upright somatomotor map in the posterior lobe. Evidence for a third set of networks was found in the most posterior extent of the cerebellum. Detailed analysis of the higher-order association networks revealed robust representations of two distinct networks linked to the default network, multiple networks linked to cognitive control, as well as a separate representation of a language network. Although idiosyncratic spatial details emerged between subjects, each network could be detected in both individuals, and seed regions placed within the cerebellum recapitulated the full extent of the spatially specific cerebral networks. The observation of multiple networks in juxtaposed regions at the Crus I/II apex confirms the importance of this zone to higher-order cognitive function and reveals new organizational details.
Access this article: https://doi.org/10.1152/jn.00561.2020
Title: The Alzheimer’s Association international guidelines for handling of cerebrospinal fluid for routine clinical measurements of amyloid β and tau
Authors: Oskar Hansson, Richard Batrla, Britta Brix, Maria C. Carrillo, Veronika Corradini, Rebecca M. Edelmayer, Rianne N. Esquivel, Christina Hall, John Lawson, Nathalie Le Bastard, José Luis Molinuevo, Laura K. Nisenbaum, Sandra Rutz, Salvatore J. Salamone, Charlotte E. Teunissen, Christopher Traynham, Robert M. Umek, Hugo Vanderstichele, Manu Vandijck, Simone Wahl, Christopher J. Weber, Henrik Zetterberg, Kaj Blennow
Type: Perspective of Alzheimer’s & Dementia
The core cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarkers amyloid beta (Aβ42 and Aβ40), total tau, and phosphorylated tau, have been extensively clinically validated, with very high diagnostic performance for AD, including the early phases of the disease. However, between-center differences in pre-analytical procedures may contribute to variability in measurements across laboratories. To resolve this issue, a workgroup was led by the Alzheimer’s Association with experts from both academia and industry. The aim of the group was to develop a simplified and standardized pre-analytical protocol for CSF collection and handling before analysis for routine clinical use, and ultimately to ensure high diagnostic performance and minimize patient misclassification rates. Widespread application of the protocol would help minimize variability in measurements, which would facilitate the implementation of unified cut-off levels across laboratories, and foster the use of CSF biomarkers in AD diagnostics for the benefit of the patients.
Access this article: https://doi.org/10.1002/alz.12316
Title: Segregation of functional networks is associated with cognitive resilience in Alzheimer’s disease
Authors: Michael Ewers, Ying Luan, Lukas Frontzkowski, Julia Neitzel, Anna Rubinski, Martin Dichgans, Jason Hassenstab, Brian A Gordon, Jasmeer P Chhatwal, Johannes Levin, Peter Schofield, Tammie L S Benzinger, John C Morris, Alison Goate, Celeste M Karch, Anne M Fagan, Eric McDade, Ricardo Allegri, Sarah Berman, Helena Chui, Carlos Cruchaga, Marty Farlow, Neill Graff-Radford, Mathias Jucker, Jae-Hong Lee, Ralph N Martins, Hiroshi Mori, Richard Perrin, Chengjie Xiong, Martin Rossor, Nick C Fox, Antoinette O’Connor, Stephen Salloway, Adrian Danek, Katharina Buerger, Randall J Bateman, Christian Habeck, Yaakov Stern, Nicolai Franzmeier, for the Alzheimer’s Disease Neuroimaging Initiative and the Dominantly Inherited Alzheimer Network
Type: Original Articles of Brain
Cognitive resilience is an important modulating factor of cognitive decline in Alzheimer’s disease, but the functional brain mechanisms that support cognitive resilience remain elusive. Given previous findings in normal ageing, we tested the hypothesis that higher segregation of the brain’s connectome into distinct functional networks represents a functional mechanism underlying cognitive resilience in Alzheimer’s disease. Using resting-state functional MRI, we assessed both resting-state functional MRI global system segregation, i.e. the balance of between-network to within-network connectivity, and the alternate index of modularity Q as predictors of cognitive resilience. We performed all analyses in two independent samples for validation: (i) 108 individuals with autosomal dominantly inherited Alzheimer’s disease and 71 non-carrier controls; and (ii) 156 amyloid-PET-positive subjects across the spectrum of sporadic Alzheimer’s disease and 184 amyloid-negative controls. In the autosomal dominant Alzheimer’s disease sample, disease severity was assessed by estimated years from symptom onset. In the sporadic Alzheimer’s sample, disease stage was assessed by temporal lobe tau-PET (i.e. composite across Braak stage I and III regions). In both samples, we tested whether the effect of disease severity on cognition was attenuated at higher levels of functional network segregation. For autosomal dominant Alzheimer’s disease, we found higher functional MRI-assessed system segregation to be associated with an attenuated effect of estimated years from symptom onset on global cognition (P = 0.007). Similarly, for patients with sporadic Alzheimer’s disease, higher functional MRI-assessed system segregation was associated with less decrement in global cognition (P = 0.001) and episodic memory (P = 0.004) per unit increase of temporal lobe tau-PET. Confirmatory analyses using the alternate index of modularity Q revealed consistent results. In conclusion, higher segregation of functional connections into distinct large-scale networks supports cognitive resilience in Alzheimer’s disease.
Access this article: https://doi.org/10.1093/brain/awab112