Brain connectivity studied by fMRI: homologous network organization in the rat, monkey, and human

The mammalian brain is composed of functional networks operating at different spatial and temporal scales — characterized by patterns of interconnections linking sensory, motor, and cognitive systems. Assessment of brain connectivity has revealed that the structure and dynamics of large-scale network organization are altered in multiple disease states suggesting their use as diagnostic or prognostic indicators. Further investigation into the underlying mechanisms, organization, and alteration of large-scale brain networks requires homologous animal models that would allow neurophysiological recordings and experimental manipulations. My current dissertation presents a comprehensive assessment and comparison of rat, macaque, and human brain networks based on evaluation of intrinsic low-frequency fluctuations of the blood oxygen-level-dependent (BOLD) fMRI signal. The signal fluctuations, recorded in the absence of any task paradigm, have been shown to reflect anatomical connectivity and are presumed to be a hemodynamic manifestation of slow fluctuations in neuronal activity. Importantly, the technique circumvents many practical limitations of other methodologies and can be compared directly between multiple species. Networks of all species were found underlying multiple levels of sensory, motor, and cognitive processing. Remarkable homologous functional connectivity was found across all species, however network complexity was dramatically increased in primate compared to rodent species. Spontaneous temporal dynamics of the resting-state networks were also preserved across species. The results demonstrate that rats and macaques share remarkable homologous network organization with humans, thereby providing strong support for their use as an animal model in the study of normal and abnormal brain connectivity as well as aiding the interpretation of electrophysiological recordings within the context of large-scale brain networks

Investigating the dynamic role of fluctuations in ongoing activity in the human brain

Traditionally, the focus in cognitive neuroscience has been on so-called evoked neural activity in response to certain stimuli or experiences. However, most of the brain’s activity is actually spontaneous and therefore not ascribed to the processing of a certain task or stimulus – or in other words, uncoupled to overt stimuli or motor outputs. In this thesis I investigated the functional role of spontaneous activity with a focus on its role in contextual changes ranging from recent experiences of individuals to trial-by-trial variability in a certain task. I studied the nature of ongoing activity from two perspectives: One looking at changes in the ongoing activity due to learning, and the other one looking at the predictive role of prestimulus activity using different methodologies, i.e. EEG and fMRI. Finally, I ventured into the realm of inter-individual differences and mind-wandering to investigate the relationship between ongoing activity, certain behavioural traits and neuronal connectivity

Spontaneous eye movements during focused-attention mindfulness meditation

Oculometric measures have been proven to be useful markers of mind-wandering during visual tasks such as reading. However, little is known about ocular activity during mindfulness meditation, a mental practice naturally involving mind-wandering episodes. In order to explore this issue, we extracted closed-eyes ocular movement measurements via a covert technique (EEG recordings) from expert meditators during two repetitions of a 7-minute mindfulness meditation session, focusing on the breath, and two repetitions of a 7-minute instructed mind-wandering task. Power spectral density was estimated on both the vertical and horizontal components of eye movements. The results show a significantly smaller average amplitude of eye movements in the delta band (1\u20134 Hz) during mindfulness meditation than instructed mind-wandering. Moreover, participants\u2019 meditation expertise correlated significantly with this average amplitude during both tasks, with more experienced meditators generally moving their eyes less than less experienced meditators. These findings suggest the potential use of this measure to detect mind-wandering episodes during mindfulness meditation and to assess meditation performance

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