Latency analysis of resting-state BOLD-fMRI reveals traveling waves in visual cortex linking task-positive and task-negative networks

Due to the low temporal resolution of BOLD-fMRI, imaging studies on human brain function have almost exclusively focused on instantaneous correlations within the data. Developments in hardware and acquisition protocols, however, are offering data with higher sampling rates that allow investigating the latency structure of BOLD-fMRI data. In this study we describe a method for analyzing the latency structure within BOLD-fMRI data and apply it to resting-state data of 94 participants from the Human Connectome Project. The method shows that task-positive and task-negative networks are integrated through traveling BOLD waves within early visual cortex. The waves are initiated at the periphery of the visual field and propagate towards the fovea. This observation suggests a mechanism for the functional integration of task-positive and task-negative networks, argues for an eccentricity-based view on visual information processing, and contributes to the emerging view that resting-state BOLD-fMRI fluctuations are superpositions of inherently spatiotemporal patterns

Quasi-periodic patterns of brain intrinsic activity coordinate the functional connections in humans

The brain is a complex self-organizing biophysical system and intrinsically very active. How such intrinsic activity organizes the brain in humans is widely being studied during resting-state using functional magnetic resonance imaging (rsfMRI) and the functional connectivity (FC) metric. FC, calculated as the Pearson correlation between rsfMRI timeseries from different brain areas, indicates coherent activity on average over time, and can reflect some spatial aspects of the brain’s intrinsic organization. For example, based on the FC profile of each area, the cerebral cortex can be parcellated into a few resting-state networks (RSNs) or exhibit a few functional connectivity gradients (FCGs). Brain is a complex system and exhibits varied dynamic spatiotemporal regimes of coherent activity, which are still poorly understood. A subset of such regimes should be giving rise to FC, yet they might entail significantly insightful aspects about the brain’s self-organizing processes, which cannot be captured by FC. Among such dynamic regimes is the quasi-periodic pattern (QPP), obtained by identifying and averaging similar ~20s-long segments of rsfMRI timeseries. QPP involves a cycle of activation and deactivation of different areas with different timings, such that the overall activity within QPP resembles RSNs and FCGs, suggesting QPP might be contributing to FC. To robustly detect multiple QPPs, method improvements were implemented and three primary QPPs were thoroughly characterized. Within these QPPs activity propagates along the functional gradients at the cerebral cortex and most subcortical regions, in a well-coordinated way, because of the consistencies and synchronies across all brain regions which reasonably accord with the consensus on the structural connections. Nuanced timing differences between regions and the closed flow of activity throughout the brain suggest drivers for these patterns. When three QPPs are removed from rsfMRI timeseries, FC within and particularly between RSNs remarkably reduces, illustrating their dominant contribution. Together, our results suggest a few recurring spatiotemporal patterns of intrinsic activity might be dominantly coordinating the functional connections across the whole brain and serving self-organization. These intrinsic patterns possibly interact with the external tasks, affecting performance, or might provide more sensitive biomarkers in certain disorders and diseases.Ph.D

On Arousal and the Internal Regulation of Brain Function: Theory and Evidence across Modalities and Species

The brain is an organ. It is subject to the same physiological regulatory processes that engage the rest of the body’s organs, sculpted over hundreds of millions of years to sustain life so effectively. The central message of this thesis is that the holistic functioning of the brain, rather than operating at some level above or independent from these systemic regulatory processes, is deeply related to them. In short, as our limited attention spans might suggest: brain function is internally regulated. I propose that this internal regulation is a primary function of intrinsic brain activity. Chapter 2 provides a theoretical treatment of this issue, recasting intrinsic activity as an internal regulatory process operating on the brain’s temporal “states” and spatial “networks”. After establishing this framework, Chapters 3 and 4 provide tests of specific predictions. Thus, Chapter 3 confirms, in humans and macaque monkeys, the presence of topographically organized traveling waves occurring in synchrony with ongoing arousal fluctuations, with propagation occurring in parallel within the neocortex, striatum, thalamus, and cerebellum. This process is argued to provide a heretofore lacking physiological account of “resting-state functional connectivity” and related phenomenology. Chapter 4 extends this observation by demonstrating a continuous and tightly coordinated temporal evolution of brain, body, and behavioral states along a latent arousal cycle. Across multiple recording techniques and species, this cyclic trajectory is shown to be coupled to the traveling wave process described in Chapter 3, thus providing a parsimonious and integrative account of intrinsic brain activity and its spatiotemporal dynamics. Taken together, this thesis argues for the existence of an intrinsic regulatory process for global brain function