LARGE-SCALE NEURAL NETWORK MODELING: FROM NEURONAL MICROCIRCUITS TO WHOLE-BRAIN COMPLEX NETWORK DYNAMICS

Neural networks mediate human cognitive functions, such as sensory processing, memory, attention, etc. Computational modeling has been proved as a powerful tool to test hypothesis of network mechanisms underlying cognitive functions, and to understand better human neuroimaging data. The dissertation presents a large-scale neural network modeling study of human brain visual/auditory processing and how this process interacts with memory and attention. We first modeled visual and auditory objects processing and short-term memory with local microcircuits and a large-scale recurrent network. We proposed a biologically realistic network implementation of storing multiple items in short-term memory. We then realized the effect that people involuntarily switch attention to salient distractors and are difficult to distract when attending to salient stimuli, by incorporating exogenous and endogenous attention modules. The integrated model could perform a number of cognitive tasks utilizing different cognitive functions by only changing a task-specification parameter. Based on the performance and simulated imaging results of these tasks, we proposed hypothesis for the neural mechanism beneath several important phenomena, which may be tested experimentally in the future. Theory of complex network has been applied in the analysis of neuroimaging data, as it provides a topological abstraction of the human brain. We constructed functional connectivity networks for various simulated experimental conditions. A number of important network properties were studied, including the scale-free property, the global efficiency, modular structure, and explored their relations with task complexity. We showed that these network properties and their dynamics of our simulated networks matched empirical studies, which verifies the validity and importance of our modeling work in testing neural network hypothesis

Computational neurorehabilitation: modeling plasticity and learning to predict recovery

Despite progress in using computational approaches to inform medicine and neuroscience in the last 30 years, there have been few attempts to model the mechanisms underlying sensorimotor rehabilitation. We argue that a fundamental understanding of neurologic recovery, and as a result accurate predictions at the individual level, will be facilitated by developing computational models of the salient neural processes, including plasticity and learning systems of the brain, and integrating them into a context specific to rehabilitation. Here, we therefore discuss Computational Neurorehabilitation, a newly emerging field aimed at modeling plasticity and motor learning to understand and improve movement recovery of individuals with neurologic impairment. We first explain how the emergence of robotics and wearable sensors for rehabilitation is providing data that make development and testing of such models increasingly feasible. We then review key aspects of plasticity and motor learning that such models will incorporate. We proceed by discussing how computational neurorehabilitation models relate to the current benchmark in rehabilitation modeling – regression-based, prognostic modeling. We then critically discuss the first computational neurorehabilitation models, which have primarily focused on modeling rehabilitation of the upper extremity after stroke, and show how even simple models have produced novel ideas for future investigation. Finally, we conclude with key directions for future research, anticipating that soon we will see the emergence of mechanistic models of motor recovery that are informed by clinical imaging results and driven by the actual movement content of rehabilitation therapy as well as wearable sensor-based records of daily activity

The explanatory power of activity flow models of brain function

Tremendous neuroscientific progress has recently been made by mapping brain connectivity, complementing extensive knowledge of task-evoked brain activation patterns. However, despite evidence that they are related, these connectivity and activity lines of research have mostly progressed separately. Here I review the notable productivity and future promise of combining connectivity and task-evoked activity estimates into activity flow models. These data-driven computational models simulate the generation of task-evoked activations (including those linked to behavior), producing empirically-supported explanations of the origin of neurocognitive functions based on the flow of task-evoked activity over empirical brain connections. Critically, by incorporating causal principles and extensive empirical constraints from brain data, this approach can provide more mechanistic accounts of neurocognitive phenomena than purely predictive (as opposed to explanatory) models or models optimized primarily for task performance (e.g., standard artificial neural networks). The variety of activity-flow-based explanations reported so far are covered here along with important methodological and theoretical considerations when discovering new activity-flow-based explanations. Together, these considerations illustrate the promise of activity flow modeling for the future of neuroscience and ultimately for the development of novel clinical treatments (e.g., using brain stimulation) for brain disorders

Modulations of Cortical Power and Connectivity in Alpha and Beta Bands during the Preparation of Reaching Movements

Planning goal-directed movements towards different targets is at the basis of common daily activities (e.g., reaching), involving visual, visuomotor, and sensorimotor brain areas. Alpha (8-13 Hz) and beta (13-30 Hz) oscillations are modulated during movement preparation and are implicated in correct motor functioning. However, how brain regions activate and interact during reaching tasks and how brain rhythms are functionally involved in these interactions is still limitedly explored. Here, alpha and beta brain activity and connectivity during reaching preparation are investigated at EEG-source level, considering a network of task-related cortical areas. Sixty-channel EEG was recorded from 20 healthy participants during a delayed center-out reaching task and projected to the cortex to extract the activity of 8 cortical regions per hemisphere (2 occipital, 2 parietal, 3 peri-central, 1 frontal). Then, we analyzed event-related spectral perturbations and directed connectivity, computed via spectral Granger causality and summarized using graph theory centrality indices (in degree, out degree). Results suggest that alpha and beta oscillations are functionally involved in the preparation of reaching in different ways, with the former mediating the inhibition of the ipsilateral sensorimotor areas and disinhibition of visual areas, and the latter coordinating disinhibition of the contralateral sensorimotor and visuomotor areas

Imaging the spatial-temporal neuronal dynamics using dynamic causal modelling

Oscillatory brain activity is a ubiquitous feature of neuronal dynamics and the synchronous discharge of neurons is believed to facilitate integration both within functionally segregated brain areas and between areas engaged by the same task. There is growing interest in investigating the neural oscillatory networks in vivo. The aims of this thesis are to (1) develop an advanced method, Dynamic Causal Modelling for Induced Responses (DCM for IR), for modelling the brain network functions and (2) apply it to exploit the nonlinear coupling in the motor system during hand grips and the functional asymmetries during face perception. DCM for IR models the time-varying power over a range of frequencies of coupled electromagnetic sources. The model parameters encode coupling strength among areas and allows the differentiations between linear (within frequency) and nonlinear (between-frequency) coupling. I applied DCM for IR to show that, during hand grips, the nonlinear interactions among neuronal sources in motor system are essential while intrinsic coupling (within source) is very likely to be linear. Furthermore, the normal aging process alters both the network architecture and the frequency contents in the motor network. I then use the bilinear form of DCM for IR to model the experimental manipulations as the modulatory effects. I use MEG data to demonstrate functional asymmetries between forward and backward connections during face perception: Specifically, high (gamma) frequencies in higher cortical areas suppressed low (alpha) frequencies in lower areas. This finding provides direct evidence for functional asymmetries that is consistent with anatomical and physiological evidence from animal studies. Lastly, I generalize the bilinear form of DCM for IR to dissociate the induced responses from evoked ones in terms of their functional role. The backward modulatory effect is expressed as induced, but not evoked responses

Issues and recommendations from the OHBM COBIDAS MEEG committee for reproducible EEG and MEG research

The Organization for Human Brain Mapping (OHBM) has been active in advocating for the instantiation of best practices in neuroimaging data acquisition, analysis, reporting and sharing of both data and analysis code to deal with issues in science related to reproducibility and replicability. Here we summarize recommendations for such practices in magnetoencephalographic (MEG) and electroencephalographic (EEG) research, recently developed by the OHBM neuroimaging community known by the abbreviated name of COBIDAS MEEG. We discuss the rationale for the guidelines and their general content, which encompass many topics under active discussion in the field. We highlight future opportunities and challenges to maximizing the sharing and exploitation of MEG and EEG data, and we also discuss how this ‘living’ set of guidelines will evolve to continually address new developments in neurophysiological assessment methods and multimodal integration of neurophysiological data with other data types.Peer reviewe

High-Density Diffuse Optical Tomography During Passive Movie Viewing: A Platform for Naturalistic Functional Brain Mapping

Human neuroimaging techniques enable researchers and clinicians to non-invasively study brain function across the lifespan in both healthy and clinical populations. However, functional brain imaging methods such as functional magnetic resonance imaging (fMRI) are expensive, resource-intensive, and require dedicated facilities, making these powerful imaging tools generally unavailable for assessing brain function in settings demanding open, unconstrained, and portable neuroimaging assessments. Tools such as functional near-infrared spectroscopy (fNIRS) afford greater portability and wearability, but at the expense of cortical field-of-view and spatial resolution. High-Density Diffuse Optical Tomography (HD-DOT) is an optical neuroimaging modality directly addresses the image quality limitations associated with traditional fNIRS techniques through densely overlapping optical measurements. This thesis aims to establish the feasibility of using HD-DOT in a novel application demanding exceptional portability and flexibility: mapping disrupted cortical activity in chronically malnourished children. I first motivate the need for dense optical measurements of brain tissue to achieve fMRI-comparable localization of brain function (Chapter 2). Then, I present imaging work completed in Cali, Colombia, where a cohort of chronically malnourished children were imaged using a custom HD-DOT instrument to establish feasibility of performing field-based neuroimaging in this population (Chapter 3). Finally, in order to meet the need for age appropriate imaging paradigms in this population, I develop passive movie viewing paradigms for use in optical neuroimaging, a flexible and rich stimulation paradigm that is suitable for both adults and children (Chapter 4)

On Control Systems of the Brain: A Study of Their Connections, Activations, and Interactions

Implementation of daily functions in humans crucially relies on both the bottom-up moment-to- moment processing of relevant input and output information as well as the top-down controls that instantiate and regulate goal-directed strategies. The current dissertation focuses on different systems of brain regions related to task control. We are interested in investigating, in detail, some of the basic activity patterns that different control systems carry during simple tasks, and how differences in activity patterns may shed new insight onto the distinctions among the systems\u27 functional roles. In addition, carefully coordinated interactions between brain regions specialized for control-related activity and regions specialized for bottom-up information processing are essential for humans to adeptly undertake various goal-directed tasks. Hence, another goal is to explore how the relationships among regions related to control and regions related to processing will change as result of top-down control signals during tasks. In Chapter 2, we applied the graph theory method of link communities onto the brain\u27s resting-state intrinsic connectivity structure to identify possible points of interactions among the previously defined functional systems, including various control systems. In Chapter 3, we conducted a meta-analysis of tasks to examine the distinct functional characteristics of control systems in task activation. Using a data-driven clustering analysis, we identified two distinct trial-related response profiles that divided the regions of control systems into a right frontoparietal and cinguloopercular cluster, which may be engaged in fine-tuning task parameters and evaluating performance, and a left frontoparietal and dorsal attention cluster, which may be involved in timely updates of trial-wise parameters as well as information processing. In Chapter 4, we explored the changes in functional relationships among selected systems during individual trials of a goal-direct task and found the presence of complex and dynamic relationships that suggest changes among the various functional systems across a trial reflect both continuous as well as momentary effects of top-down signals. Collectively, the studies presented here both contributed to as well as challenged previous frameworks of task control in an effort to build better understanding of the basic organization and interactions among the brain\u27s functional systems