Auditory network connectivity in tinnitus patients: a resting-state fMRI study

Objective: Resting-state functional magnetic resonance imaging (fMRI) uncovers correlated activity between spatially distinct functionally related brain regions and offers clues about the integrity of functional brain circuits in people with chronic subjective tinnitus. We chose to investigate auditory network connectivity, adopting and extending previously used analyses methods to provide an independent evaluation of replicability. Design: Independent components analysis (ICA) was used to identify coherent patterns arising from spontaneous brain signals within the resting-state data. The auditory network component was extracted and evaluated. Bivariate and partial correlation analyses were performed on pre-defined regions of bilateral auditory cortex to assess functional connectivity. Study sample: Our design carefully matched participant groups for possible confounds, such as hearing status. Twelve patients (seven male, five female; mean age 66 years) all with chronic constant tinnitus and eleven controls (eight male, three female; mean age 68 years) took part. Results: No significant differences were found in auditory network connectivity between groups after correcting for multiple statistical comparisons in the analysis. This contradicts previous findings reporting reduced auditory network connectivity; albeit at a less stringent statistical threshold. Conclusions: Auditory network connectivity does not appear to be reliably altered by the experience of chronic subjective tinnitus

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Transport on Riemannian Manifold for Functional Connectivity-based Classification

International audienceWe present a Riemannian approach for classifying fMRI connectivity patterns before and after intervention in longitudinal studies. A fundamental difficulty with using connectivity as features is that covariance matrices live on the positive semi-definite cone, which renders their elements inter-related. The implicit independent feature assumption in most classifier learning algorithms is thus violated. In this paper, we propose a matrix whitening transport for projecting the covariance estimates onto a common tangent space to reduce the statistical dependencies between their elements. We show on real data that our approach provides significantly higher classification accuracy than directly using Pearson's correlation. We further propose a non-parametric scheme for identifying significantly discriminative connections from classifier weights. Using this scheme, a number of neuroanatomically meaningful connections are found, whereas no significant connections are detected with pure permutation testing

Mnemonic Training Reshapes Brain Networks to Support Superior Memory

Memory skills strongly differ across the general population; however, little is known about the brain characteristics supporting superior memory performance. Here we assess functional brain network organization of 23 of the world's most successful memory athletes and matched controls with fMRI during both task-free resting state baseline and active memory encoding. We demonstrate that, in a group of naive controls, functional connectivity changes induced by 6 weeks of mnemonic training were correlated with the network organization that distinguishes athletes from controls. During rest, this effect was mainly driven by connections between rather than within the visual, medial temporal lobe and default mode networks, whereas during task it was driven by connectivity within these networks. Similarity with memory athlete connectivity patterns predicted memory improvements up to 4 months after training. In conclusion, mnemonic training drives distributed rather than regional changes, reorganizing the brain's functional network organization to enable superior memory performance