Fully Bayesian Inference for Structural MRI: Application to Segmentation and Statistical Analysis of T2-Hypointensities.

Aiming at iron-related T2-hypointensity, which is related to normal aging and neurodegenerative processes, we here present two practicable approaches, based on Bayesian inference, for preprocessing and statistical analysis of a complex set of structural MRI data. In particular, Markov Chain Monte Carlo methods were used to simulate posterior distributions. First, we rendered a segmentation algorithm that uses outlier detection based on model checking techniques within a Bayesian mixture model. Second, we rendered an analytical tool comprising a Bayesian regression model with smoothness priors (in the form of Gaussian Markov random fields) mitigating the necessity to smooth data prior to statistical analysis. For validation, we used simulated data and MRI data of 27 healthy controls (age: [Formula: see text]; range, [Formula: see text]). We first observed robust segmentation of both simulated T2-hypointensities and gray-matter regions known to be T2-hypointense. Second, simulated data and images of segmented T2-hypointensity were analyzed. We found not only robust identification of simulated effects but also a biologically plausible age-related increase of T2-hypointensity primarily within the dentate nucleus but also within the globus pallidus, substantia nigra, and red nucleus. Our results indicate that fully Bayesian inference can successfully be applied for preprocessing and statistical analysis of structural MRI data

How to avoid mismodelling in GLM-based fMRI data analysis: cross-validated Bayesian model selection

Voxel-wise general linear models (GLMs) are a standard approach for analyzing functional magnetic resonance imaging (fMRI) data. An advantage of GLMs is that they are flexible and can be adapted to the requirements of many different data sets. However, the specification of first-level GLMs leaves the researcher with many degrees of freedom which is problematic given recent efforts to ensure robust and reproducible fMRI data analysis. Formal model comparisons that allow a systematic assessment of GLMs are only rarely performed. On the one hand, too simple models may underfit data and leave real effects undiscovered. On the other hand, too complex models might overfit data and also reduce statistical power. Here we present a systematic approach termed cross-validated Bayesian model selection (cvBMS) that allows to decide which GLM best describes a given fMRI data set. Importantly, our approach allows for non-nested model comparison, i.e. comparing more than two models that do not just differ by adding one or more regressors. It also allows for spatially heterogeneous modelling, i.e. using different models for different parts of the brain. We validate our method using simulated data and demonstrate potential applications to empirical data. The increased use of model comparison and model selection should increase the reliability of GLM results and reproducibility of fMRI studies

Predictive decoding of neural data

In the last five decades the number of techniques available for non-invasive functional imaging has increased dramatically. Researchers today can choose from a variety of imaging modalities that include EEG, MEG, PET, SPECT, MRI, and fMRI. This doctoral dissertation offers a methodology for the reliable analysis of neural data at different levels of investigation. By using statistical learning algorithms the proposed approach allows single-trial analysis of various neural data by decoding them into variables of interest. Unbiased testing of the decoder on new samples of the data provides a generalization assessment of decoding performance reliability. Through consecutive analysis of the constructed decoder\u27s sensitivity it is possible to identify neural signal components relevant to the task of interest. The proposed methodology accounts for covariance and causality structures present in the signal. This feature makes it more powerful than conventional univariate methods which currently dominate the neuroscience field. Chapter 2 describes the generic approach toward the analysis of neural data using statistical learning algorithms. Chapter 3 presents an analysis of results from four neural data modalities: extracellular recordings, EEG, MEG, and fMRI. These examples demonstrate the ability of the approach to reveal neural data components which cannot be uncovered with conventional methods. A further extension of the methodology, Chapter 4 is used to analyze data from multiple neural data modalities: EEG and fMRI. The reliable mapping of data from one modality into the other provides a better understanding of the underlying neural processes. By allowing the spatial-temporal exploration of neural signals under loose modeling assumptions, it removes potential bias in the analysis of neural data due to otherwise possible forward model misspecification. The proposed methodology has been formalized into a free and open source Python framework for statistical learning based data analysis. This framework, PyMVPA, is described in Chapter 5

A Behavioral and Neural Evaluation of Prospective Decision-Making under Risk

Making the best choice when faced with a chain of decisions requires a person to judge both anticipated outcomes and future actions. Although economic decision-making models account for both risk and reward in single-choice contexts, there is a dearth of similar knowledge about sequential choice. Classical utility-based models assume that decision-makers select and follow an optimal predetermined strategy, regardless of the particular order in which options are presented. An alternative model involves continuously reevaluating decision utilities, without prescribing a specific future set of choices. Here, using behavioral and functional magnetic resonance imaging (fMRI) data, we studied human subjects in a sequential choice task and use these data to compare alternative decision models of valuation and strategy selection. We provide evidence that subjects adopt a model of reevaluating decision utilities, in which available strategies are continuously updated and combined in assessing action values. We validate this model by using simultaneously acquired fMRI data to show that sequential choice evokes a pattern of neural response consistent with a tracking of anticipated distribution of future reward, as expected in such a model. Thus, brain activity evoked at each decision point reflects the expected mean, variance, and skewness of possible payoffs, consistent with the idea that sequential choice evokes a prospective evaluation of both available strategies and possible outcomes

Paradoxical lesions, plasticity and active inference

Paradoxical lesions are secondary brain lesions that ameliorate functional deficits caused by the initial insult. This effect has been explained in several ways; particularly by the reduction of functional inhibition, or by increases in the excitatory-to-inhibitory synaptic balance within perilesional tissue. In this article, we simulate how and when a modification of the excitatory–inhibitory balance triggers the reversal of a functional deficit caused by a primary lesion. For this, we introduce in-silico lesions to an active inference model of auditory word repetition. The first in-silico lesion simulated damage to the extrinsic (between regions) connectivity causing a functional deficit that did not fully resolve over 100 trials of a word repetition task. The second lesion was implemented in the intrinsic (within region) connectivity, compromising the model’s ability to rebalance excitatory–inhibitory connections during learning. We found that when the second lesion was mild, there was an increase in experience-dependent plasticity that enhanced performance relative to a single lesion. This paradoxical lesion effect disappeared when the second lesion was more severe because plasticity-related changes were disproportionately amplified in the intrinsic connectivity, relative to lesioned extrinsic connections. Finally, this framework was used to predict the physiological correlates of paradoxical lesions. This formal approach provides new insights into the computational and neurophysiological mechanisms that allow some patients to recover after large or multiple lesions