Structure Learning in Coupled Dynamical Systems and Dynamic Causal Modelling

Identifying a coupled dynamical system out of many plausible candidates, each of which could serve as the underlying generator of some observed measurements, is a profoundly ill posed problem that commonly arises when modelling real world phenomena. In this review, we detail a set of statistical procedures for inferring the structure of nonlinear coupled dynamical systems (structure learning), which has proved useful in neuroscience research. A key focus here is the comparison of competing models of (ie, hypotheses about) network architectures and implicit coupling functions in terms of their Bayesian model evidence. These methods are collectively referred to as dynamical casual modelling (DCM). We focus on a relatively new approach that is proving remarkably useful; namely, Bayesian model reduction (BMR), which enables rapid evaluation and comparison of models that differ in their network architecture. We illustrate the usefulness of these techniques through modelling neurovascular coupling (cellular pathways linking neuronal and vascular systems), whose function is an active focus of research in neurobiology and the imaging of coupled neuronal systems

Advancing functional connectivity research from association to causation

Cognition and behavior emerge from brain network interactions, such that investigating causal interactions should be central to the study of brain function. Approaches that characterize statistical associations among neural time series-functional connectivity (FC) methods-are likely a good starting point for estimating brain network interactions. Yet only a subset of FC methods ('effective connectivity') is explicitly designed to infer causal interactions from statistical associations. Here we incorporate best practices from diverse areas of FC research to illustrate how FC methods can be refined to improve inferences about neural mechanisms, with properties of causal neural interactions as a common ontology to facilitate cumulative progress across FC approaches. We further demonstrate how the most common FC measures (correlation and coherence) reduce the set of likely causal models, facilitating causal inferences despite major limitations. Alternative FC measures are suggested to immediately start improving causal inferences beyond these common FC measures

Characterizing dynamically evolving functional networks in humans with application to speech

Understanding how communication between brain areas evolves to support dynamic function remains a fundamental challenge in neuroscience. One approach to this question is functional connectivity analysis, in which statistical coupling measures are employed to detect signatures of interactions between brain regions. Because the brain uses multiple communication mechanisms at different temporal and spatial scales, and because the neuronal signatures of communication are often weak, powerful connectivity inference methodologies require continued development specific to these challenges. Here we address the challenge of inferring task-related functional connectivity in brain voltage recordings. We first develop a framework for detecting changes in statistical coupling that occur reliably in a task relative to a baseline period. The framework characterizes the dynamics of connectivity changes, allows inference on multiple spatial scales, and assesses statistical uncertainty. This general framework is modular and applicable to a wide range of tasks and research questions. We demonstrate the flexibility of the framework in the second part of this thesis, in which we refine the coupling statistics and hypothesis tests to improve statistical power and test different proposed connectivity mechanisms. In particular, we introduce frequency domain coupling measures and define test statistics that exploit theoretical properties and capture known sampling variability. The resulting test statistics use correlation, coherence, canonical correlation, and canonical coherence to infer task-related changes in coupling. Because canonical correlation and canonical coherence are not commonly used in functional connectivity analyses, we derive the theoretical values and statistical estimators for these measures. In the third part of this thesis, we present a sample application of these techniques to electrocorticography data collected during an overt reading task. We discuss the challenges that arise with task-related human data, which is often noisy and underpowered, and present functional connectivity results in the context of traditional and contemporary within-electrode analytics. In two of nine subjects we observe time-domain and frequency-domain network changes that accord with theoretical models of information routing during motor processing. Taken together, this work contributes a methodological framework for inferring task-related functional connectivity across spatial and temporal scales, and supports insight into the rapid, dynamic functional coupling of human speech

Caffeine-Induced Global Reductions in Resting-State BOLD Connectivity Reflect Widespread Decreases in MEG Connectivity.

In resting-state functional magnetic resonance imaging (fMRI), the temporal correlation between spontaneous fluctuations of the blood oxygenation level dependent (BOLD) signal from different brain regions is used to assess functional connectivity. However, because the BOLD signal is an indirect measure of neuronal activity, its complex hemodynamic nature can complicate the interpretation of differences in connectivity that are observed across conditions or subjects. For example, prior studies have shown that caffeine leads to widespread reductions in BOLD connectivity but were not able to determine if neural or vascular factors were primarily responsible for the observed decrease. In this study, we used source-localized magnetoencephalography (MEG) in conjunction with fMRI to further examine the origins of the caffeine-induced changes in BOLD connectivity. We observed widespread and significant (p < 0.01) reductions in both MEG and fMRI connectivity measures, suggesting that decreases in the connectivity of resting-state neuro-electric power fluctuations were primarily responsible for the observed BOLD connectivity changes. The MEG connectivity decreases were most pronounced in the beta band. By demonstrating the similarity in MEG and fMRI based connectivity changes, these results provide evidence for the neural basis of resting-state fMRI networks and further support the potential of MEG as a tool to characterize resting-state connectivity

Dopamine restores reward prediction errors in old age.

Senescence affects the ability to utilize information about the likelihood of rewards for optimal decision-making. Using functional magnetic resonance imaging in humans, we found that healthy older adults had an abnormal signature of expected value, resulting in an incomplete reward prediction error (RPE) signal in the nucleus accumbens, a brain region that receives rich input projections from substantia nigra/ventral tegmental area (SN/VTA) dopaminergic neurons. Structural connectivity between SN/VTA and striatum, measured by diffusion tensor imaging, was tightly coupled to inter-individual differences in the expression of this expected reward value signal. The dopamine precursor levodopa (L-DOPA) increased the task-based learning rate and task performance in some older adults to the level of young adults. This drug effect was linked to restoration of a canonical neural RPE. Our results identify a neurochemical signature underlying abnormal reward processing in older adults and indicate that this can be modulated by L-DOPA

Learning under uncertainty in the young and older human brain: Common and distinct mechanisms of different attentional and intentional systems

The human brain is able to infer the probability of future events by combining information of past observations with current sensory input. Naturally, we are surrounded by more stimuli than we can pay attention to, so selection of relevant input is crucial. The present thesis aimed at identifying common and distinct neural correlates engaged in predictive processing in spatial attention (selection of attended locations) and motor intention (selection of prepared motor responses). Secondly, age-related influences on probabilistic inference in spatial-attention, feature-based attention (selection of attended color) and motor intention, and the impact of task difficulty were considered. Orienting attention during goal-directed behavior can be supported by visual cues, whereas reorienting to unexpected events following misguiding information is linked to behavioral costs and updating of predictions. These processes can be investigated with a cueing paradigm in which differences in reaction time (RT) between valid and invalidly cued trials increase with higher cue validity (%CV) (Posner, 1980). Bayesian models can describe the experience-dependent learning effects of inferring %CV, following novel events (Vossel et al., 2014c; Vossel, Mathys, Stephan & Friston, 2015). The principle aim of the first experiment was to identify and compare the neural correlates involved in inferring probabilities in the spatial attentional and motor intentional domain. Cues indicated either the possible location or prepared the motor response associated with the target. Instead of a fixed probability context, participants were exposed to a volatile environment, in which the validity of the cue information changed unpredictably over time. Combining functional magnetic resonance imaging (fMRI) data with behavioral estimates derived from a Bayesian learning model (Mathys, Daunizeau, Friston & Stephan, 2011) unveiled domain-specific predictability-dependent responses within the right temporoparietal junction (TPJ) for spatial attention and the left angular gyrus (ANG) and anterior cingulate (ACC) in the motor intention task. The blood oxygen level dependent (BOLD) amplitude particularly increased in accord with violations of cue predictability in high cue validity contexts (i.e. when invalid trials were least expected). Valid trials however, induced no (TPJ and ANG) or decreased modulation (ACC). A further aim was to examine possible commonalities in the neural signatures of predictability-dependent processing. Connectivity analysis uncovered common coupling of all three seed regions involved in predictability-dependent processing with the right anterior hippocampus. Since cognitive functions undergo substantial changes in healthy ageing, a second behavioral study was conducted to test whether age differentially influences probabilistic inference in different attentional subsystems, and how task difficulty impacts on learning performance. Thus, following up on the first experiment, similar tasks and the same computational model was used to assess updating behavior in healthy aging. Older and younger adults performed two separate experiments with different difficulty levels. Each experiment included three versions of a cueing task, entailing predictive spatial- (i.e. location), feature- (i.e. color of target) and motor intention cues (i.e. prepare response). Results of the easier version demonstrated a preserved ability of older adults to generate predictions and profit from all cue types. Interestingly, increased task demand uncovered a reduced ability to use motor intention cues to update predictions in older compared to younger adults. In conclusion, the results provide evidence for a segregated functional anatomy of probabilistic inference in spatial attention and motor intention. Nonetheless a common connectivity profile with the hippocampus also points at commonalities. Finally age seems to differentially impact the efficiency of learning behavior in the motor intention system, supporting the notion of independence of the attentional- and intentional subsystems

Attention-dependent modulation of cortical taste circuits revealed by granger causality with signal-dependent noise

We show, for the first time, that in cortical areas, for example the insular, orbitofrontal, and lateral prefrontal cortex, there is signal-dependent noise in the fMRI blood-oxygen level dependent (BOLD) time series, with the variance of the noise increasing approximately linearly with the square of the signal. Classical Granger causal models are based on autoregressive models with time invariant covariance structure, and thus do not take this signal-dependent noise into account. To address this limitation, here we describe a Granger causal model with signal-dependent noise, and a novel, likelihood ratio test for causal inferences. We apply this approach to the data from an fMRI study to investigate the source of the top-down attentional control of taste intensity and taste pleasantness processing. The Granger causality with signal-dependent noise analysis reveals effects not identified by classical Granger causal analysis. In particular, there is a top-down effect from the posterior lateral prefrontal cortex to the insular taste cortex during attention to intensity but not to pleasantness, and there is a top-down effect from the anterior and posterior lateral prefrontal cortex to the orbitofrontal cortex during attention to pleasantness but not to intensity. In addition, there is stronger forward effective connectivity from the insular taste cortex to the orbitofrontal cortex during attention to pleasantness than during attention to intensity. These findings indicate the importance of explicitly modeling signal-dependent noise in functional neuroimaging, and reveal some of the processes involved in a biased activation theory of selective attention

The relationship between MEG and fMRI

In recent years functional neuroimaging techniques such as fMRI, MEG, EEG and PET have provided researchers with a wealth of information on human brain function. However none of these modalities can measure directly either the neuro-electrical or neuro-chemical processes that mediate brain function. This means that metrics directly reflecting brain ‘activity’ must be inferred from other metrics (e.g. magnetic fields (MEG) or haemodynamics (fMRI)). To overcome this limitation, many studies seek to combine multiple complementary modalities and an excellent example of this is the combination of MEG (which has high temporal resolution) with fMRI (which has high spatial resolution). However, the full potential of multi-modal approaches can only be truly realised in cases where the relationship between metrics is known. In this paper, we explore the relationship between measurements made using fMRI and MEG. We describe the origins of the two signals as well as their relationship to electrophysiology. We review multiple studies that have attempted to characterise the spatial relationship between fMRI and MEG, and we also describe studies that exploit the rich information content of MEG to explore differing relationships between MEG and fMRI across neural oscillatory frequency bands. Monitoring the brain at “rest” has become of significant recent interest to the neuroimaging community and we review recent evidence comparing MEG and fMRI metrics of functional connectivity. A brief discussion of the use of magnetic resonance spectroscopy (MRS) to probe the relationship between MEG/fMRI and neurochemistry is also given. Finally, we highlight future areas of interest and offer some recommendations for the parallel use of fMRI and MEG