skip to main content


Title: Functional connectivity across the human subcortical auditory system using an autoregressive matrix-Gaussian copula graphical model approach with partial correlations
Abstract

The auditory system comprises multiple subcortical brain structures that process and refine incoming acoustic signals along the primary auditory pathway. Due to technical limitations of imaging small structures deep inside the brain, most of our knowledge of the subcortical auditory system is based on research in animal models using invasive methodologies. Advances in ultrahigh-field functional magnetic resonance imaging (fMRI) acquisition have enabled novel noninvasive investigations of the human auditory subcortex, including fundamental features of auditory representation such as tonotopy and periodotopy. However, functional connectivity across subcortical networks is still underexplored in humans, with ongoing development of related methods. Traditionally, functional connectivity is estimated from fMRI data with full correlation matrices. However, partial correlations reveal the relationship between two regions after removing the effects of all other regions, reflecting more direct connectivity. Partial correlation analysis is particularly promising in the ascending auditory system, where sensory information is passed in an obligatory manner, from nucleus to nucleus up the primary auditory pathway, providing redundant but also increasingly abstract representations of auditory stimuli. While most existing methods for learning conditional dependency structures based on partial correlations assume independently and identically Gaussian distributed data, fMRI data exhibit significant deviations from Gaussianity as well as high-temporal autocorrelation. In this paper, we developed an autoregressive matrix-Gaussian copula graphical model (ARMGCGM) approach to estimate the partial correlations and thereby infer the functional connectivity patterns within the auditory system while appropriately accounting for autocorrelations between successive fMRI scans. Our results show strong positive partial correlations between successive structures in the primary auditory pathway on each side (left and right), including between auditory midbrain and thalamus, and between primary and associative auditory cortex. These results are highly stable when splitting the data in halves according to the acquisition schemes and computing partial correlations separately for each half of the data, as well as across cross-validation folds. In contrast, full correlation-based analysis identified a rich network of interconnectivity that was not specific to adjacent nodes along the pathway. Overall, our results demonstrate that unique functional connectivity patterns along the auditory pathway are recoverable using novel connectivity approaches and that our connectivity methods are reliable across multiple acquisitions.

 
more » « less
Award ID(s):
1953712
PAR ID:
10543541
Author(s) / Creator(s):
; ; ;
Publisher / Repository:
MIT Press
Date Published:
Journal Name:
Imaging Neuroscience
Volume:
2
ISSN:
2837-6056
Page Range / eLocation ID:
1 to 23
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Studying dynamic-functional connectivity (DFC) using fMRI data of the brain gives much richer information to neuroscientists than studying the brain as a static entity. Mining of dynamic connectivity graphs from these brain studies can be used to classify diseased versus healthy brains. However, constructing and mining dynamic-functional connectivity graphs of the brain can be time consuming due to size of fMRI data. In this paper, we propose a highly scalable GPU-based parallel algorithm called GPU-DFC for computing dynamic-functional connectivity of fMRI data both at region and voxel level. Our algorithm exploits sparsification of correlation matrix and stores them in CSR format. Further reduction in the correlation matrix is achieved by parallel decomposition techniques. Our GPU-DFC algorithm achieves 2 times speed-up for computing dynamic correlations compared to state-of-the-art GPU-based techniques and more than 40 times compared to a sequential CPU version. In terms of storage, our proposed matrix decomposition technique reduces the size of correlation matrices more than 100 times. Reconstructed values from decomposed matrices show comparable results as compared to the correlations with original data. The implemented code is available as GPL license on GitHub portal of our lab (https://github.com/pcdslab/GPU-DFC). 
    more » « less
  2. Abstract

    Representing data using time-resolved networks is valuable for analyzing functional data of the human brain. One commonly used method for constructing time-resolved networks from data is sliding window Pearson correlation (SWPC). One major limitation of SWPC is that it applies a high-pass filter to the activity time series. Therefore, if we select a short window (desirable to estimate rapid changes in connectivity), we will remove important low-frequency information. Here, we propose an approach based on single sideband modulation (SSB) in communication theory. This allows us to select shorter windows to capture rapid changes in the time-resolved functional network connectivity (trFNC). We use simulation and real resting-state functional magnetic resonance imaging (fMRI) data to demonstrate the superior performance of SSB+SWPC compared to SWPC. We also compare the recurring trFNC patterns between individuals with the first episode of psychosis (FEP) and typical controls (TC) and show that FEPs stay more in states that show weaker connectivity across the whole brain. A result exclusive to SSB+SWPC is that TCs stay more in a state with negative connectivity between subcortical and cortical regions. Based on all the results, we argue that SSB+SWPC is more sensitive for capturing temporal variation in trFNC.

     
    more » « less
  3. Abstract

    Listening to pleasurable music is known to engage the brain’s reward system. This has motivated many cognitive-behavioral interventions for healthy aging, but little is known about the effects of music-based intervention (MBI) on activity and connectivity of the brain’s auditory and reward systems. Here we show preliminary evidence that brain network connectivity can change after receptive MBI in cognitively unimpaired older adults. Using a combination of whole-brain regression, seed-based connectivity analysis, and representational similarity analysis (RSA), we examined fMRI responses during music listening in older adults before and after an 8-week personalized MBI. Participants rated self-selected and researcher-selected musical excerpts on liking and familiarity. Parametric effects of liking, familiarity, and selection showed simultaneous activation in auditory, reward, and default mode network (DMN) areas. Functional connectivity within and between auditory and reward networks was modulated by participant liking and familiarity ratings. RSA showed significant representations of selection and novelty at both time-points, and an increase in striatal representation of musical stimuli following intervention. An exploratory seed-based connectivity analysis comparing pre- and post-intervention showed significant increase in functional connectivity between auditory regions and medial prefrontal cortex (mPFC). Taken together, results show how regular music listening can provide an auditory channel towards the mPFC, thus offering a potential neural mechanism for MBI supporting healthy aging.

     
    more » « less
  4. Abstract

    Objective. Spontaneous fluctuations of cerebral hemodynamics measured by functional magnetic resonance imaging (fMRI) are widely used to study the network organization of the brain. The temporal correlations among the ultra-slow, <0.1 Hz fluctuations across the brain regions are interpreted as functional connectivity maps and used for diagnostics of neurological disorders. However, despite the interest narrowed in the ultra-slow fluctuations, hemodynamic activity that exists beyond the ultra-slow frequency range could contribute to the functional connectivity, which remains unclear.Approach. In the present study, we have measured the brain-wide hemodynamics in the human participants with functional near-infrared spectroscopy (fNIRS) in a whole-head, cap-based and high-density montage at a sampling rate of 6.25 Hz. In addition, we have acquired resting state fMRI scans in the same group of participants for cross-modal evaluation of the connectivity maps. Then fNIRS data were deliberately down-sampled to a typical fMRI sampling rate of ∼0.5 Hz and the resulted differential connectivity maps were subject to a k-means clustering.Main results. Our diffuse optical topographical analysis of fNIRS data have revealed a default mode network (DMN) in the spontaneous deoxygenated and oxygenated hemoglobin changes, which remarkably resemble the same fMRI network derived from participants. Moreover, we have shown that the aliased activities in the down-sampled optical signals have altered the connectivity patterns, resulting in a network organization of aliased functional connectivity in the cerebral hemodynamics.Significance.The results have for the first time demonstrated that fNIRS as a broadly accessible modality can image the resting-state functional connectivity in the posterior midline, prefrontal and parietal structures of the DMN in the human brain, in a consistent pattern with fMRI. Further empowered by the fast sampling rate of fNIRS, our findings suggest the presence of aliased connectivity in the current understanding of the human brain organization.

     
    more » « less
  5. Abstract

    Quantifying the association between components of multivariate random curves is of general interest and is a ubiquitous and basic problem that can be addressed with functional data analysis. An important application is the problem of assessing functional connectivity based on functional magnetic resonance imaging (fMRI), where one aims to determine the similarity of fMRI time courses that are recorded on anatomically separated brain regions. In the functional brain connectivity literature, the static temporal Pearson correlation has been the prevailing measure for functional connectivity. However, recent research has revealed temporally changing patterns of functional connectivity, leading to the study of dynamic functional connectivity. This motivates new similarity measures for pairs of random curves that reflect the dynamic features of functional similarity. Specifically, we introduce gradient synchronization measures in a general setting. These similarity measures are based on the concordance and discordance of the gradients between paired smooth random functions. Asymptotic normality of the proposed estimates is obtained under regularity conditions. We illustrate the proposed synchronization measures via simulations and an application to resting-state fMRI signals from the Alzheimer’s Disease Neuroimaging Initiative and they are found to improve discrimination between subjects with different disease status.

     
    more » « less