skip to main content

Title: Gaussian process linking functions for mind, brain, and behavior

The link between mind, brain, and behavior has mystified philosophers and scientists for millennia. Recent progress has been made by forming statistical associations between manifest variables of the brain (e.g., electroencephalogram [EEG], functional MRI [fMRI]) and manifest variables of behavior (e.g., response times, accuracy) through hierarchical latent variable models. Within this framework, one can make inferences about the mind in a statistically principled way, such that complex patterns of brain–behavior associations drive the inference procedure. However, previous approaches were limited in the flexibility of the linking function, which has proved prohibitive for understanding the complex dynamics exhibited by the brain. In this article, we propose a data-driven, nonparametric approach that allows complex linking functions to emerge from fitting a hierarchical latent representation of the mind to multivariate, multimodal data. Furthermore, to enforce biological plausibility, we impose both spatial and temporal structure so that the types of realizable system dynamics are constrained. To illustrate the benefits of our approach, we investigate the model’s performance in a simulation study and apply it to experimental data. In the simulation study, we verify that the model can be accurately fitted to simulated data, and latent dynamics can be well recovered. In an experimental application, more » we simultaneously fit the model to fMRI and behavioral data from a continuous motion tracking task. We show that the model accurately recovers both neural and behavioral data and reveals interesting latent cognitive dynamics, the topology of which can be contrasted with several aspects of the experiment.

« less
Authors:
; ; ;
Award ID(s):
1847603
Publication Date:
NSF-PAR ID:
10202825
Journal Name:
Proceedings of the National Academy of Sciences
Volume:
117
Issue:
47
Page Range or eLocation-ID:
p. 29398-29406
ISSN:
0027-8424
Publisher:
Proceedings of the National Academy of Sciences
Sponsoring Org:
National Science Foundation
More Like this
  1. Understanding the intrinsic patterns of human brain is important to make inferences about the mind and brain-behavior association. Electrophysiological methods (i.e. MEG/EEG) provide direct measures of neural activity without the effect of vascular confounds. The blood oxygenated level-dependent (BOLD) signal of functional MRI (fMRI) reveals the spatial and temporal brain activity across different brain regions. However, it is unclear how to associate the high temporal resolution Electrophysiological measures with high spatial resolution fMRI signals. Here, we present a novel interpretable model for coupling the structure and function activity of brain based on heterogeneous contrastive graph representation. The proposed method is able to link manifest variables of the brain (i.e. MEG, MRI, fMRI and behavior performance) and quantify the intrinsic coupling strength of different modal signals. The proposed method learns the heterogeneous node and graph representations by contrasting the structural and temporal views through the mind to multimodal brain data. The first experiment with 1200 subjects from Human connectome Project (HCP) shows that the proposed method outperforms the existing approaches in predicting individual gender and enabling the location of the importance of brain regions with sex difference. The second experiment associates the structure and temporal views between the low-level sensory regionsmore »and high-level cognitive ones. The experimental results demonstrate that the dependence of structural and temporal views varied spatially through different modal variants. The proposed method enables the heterogeneous biomarkers explanation for different brain measurements.« less
  2. It is becoming increasingly common to collect multiple related neuroimaging datasets either from different modalities or from different tasks and conditions. In addition, we have non-imaging data such as cognitive or behavioral variables, and it is through the association of these two sets of data—neuroimaging and non-neuroimaging—that we can understand and explain the evolution of neural and cognitive processes, and predict outcomes for intervention and treatment. Multiple methods for the joint analysis or fusion of multiple neuroimaging datasets or modalities exist; however, methods for the joint analysis of imaging and non-imaging data are still in their infancy. Current approaches for identifying brain networks related to cognitive assessments are still largely based on simple one-to-one correlation analyses and do not use the cross information available across multiple datasets. This work proposes two approaches based on independent vector analysis (IVA) to jointly analyze the imaging datasets and behavioral variables such that multivariate relationships across imaging data and behavioral features can be identified. The simulation results show that our proposed methods provide better accuracy in identifying associations across imaging and behavioral components than current approaches. With functional magnetic resonance imaging (fMRI) task data collected from 138 healthy controls and 109 patients with schizophrenia,more »results reveal that the central executive network (CEN) estimated in multiple datasets shows a strong correlation with the behavioral variable that measures working memory, a result that is not identified by traditional approaches. Most of the identified fMRI maps also show significant differences in activations across healthy controls and patients potentially providing a useful signature of mental disorders.« less
  3. Motivated by modern applications in which one constructs graphical models based on a very large number of features, this paper introduces a new class of cluster-based graphical models, in which variable clustering is applied as an initial step for reducing the dimension of the feature space. We employ model assisted clustering, in which the clusters contain features that are similar to the same unobserved latent variable. Two different cluster-based Gaussian graphical models are considered: the latent variable graph, corresponding to the graphical model associated with the unobserved latent variables, and the cluster-average graph, corresponding to the vector of features averaged over clusters. Our study reveals that likelihood based inference for the latent graph, not analyzed previously, is analytically intractable. Our main contribution is the development and analysis of alternative estimation and inference strategies, for the precision matrix of an unobservable latent vector Z. We replace the likelihood of the data by an appropriate class of empirical risk functions, that can be specialized to the latent graphical model and to the simpler, but under-analyzed, cluster-average graphical model. The estimators thus derived can be used for inference on the graph structure, for instance on edge strength or pattern recovery. Inference is basedmore »on the asymptotic limits of the entry-wise estimates of the precision matrices associated with the conditional independence graphs under consideration. While taking the uncertainty induced by the clustering step into account, we establish Berry-Esseen central limit theorems for the proposed estimators. It is noteworthy that, although the clusters are estimated adaptively from the data, the central limit theorems regarding the entries of the estimated graphs are proved under the same conditions one would use if the clusters were known in advance. As an illustration of the usage of these newly developed inferential tools, we show that they can be reliably used for recovery of the sparsity pattern of the graphs we study, under FDR control, which is verified via simulation studies and an fMRI data analysis. These experimental results confirm the theoretically established difference between the two graph structures. Furthermore, the data analysis suggests that the latent variable graph, corresponding to the unobserved cluster centers, can help provide more insight into the understanding of the brain connectivity networks relative to the simpler, average-based, graph.« less
  4. One goal of cognitive science is to build theories of mental function that predict individual behavior. In this project we focus on predicting, for individual participants, which specific items in a list will be remembered at some point in the future. If you want to know if an individual will remember something, one commonsense approach is to give them a quiz or test such that a correct answer likely indicates later memory for an item. In this project we attempt to predict later memory without ex- plicit assessments by jointly modeling both neural and behavioral data in a computational cognitive model which captures the dynamics of memory acquisition and decay. In this paper, we lay out a novel hierarchical Bayesian approach for combining neural and behavioral data and present results showing how fMRI signals recorded during the study phase of a memory task can improve our ability to predict (in held-out data) which items will be remembered or forgotten 72 hours later.
  5. Klausberger, Thomas (Ed.)
    Understanding brain operation demands linking basic behavioral traits to cell-type specific dynamics of different brain-wide subcircuits. This requires a system to classify the basic operational modes of neurons and circuits. Single-cell phenotyping of firing behavior during ongoing oscillations in vivo has provided a large body of evidence on entorhinal–hippocampal function, but data are dispersed and diverse. Here, we mined literature to search for information regarding the phase-timing dynamics of over 100 hippocampal/entorhinal neuron types defined in Hippocampome.org . We identified missing and unresolved pieces of knowledge (e.g., the preferred theta phase for a specific neuron type) and complemented the dataset with our own new data. By confronting the effect of brain state and recording methods, we highlight the equivalences and differences across conditions and offer a number of novel observations. We show how a heuristic approach based on oscillatory features of morphologically identified neurons can aid in classifying extracellular recordings of single cells and discuss future opportunities and challenges towards integrating single-cell phenotypes with circuit function.