Person:

Bajic, Dusica

Early brain development is characterized by rapid growth and perpetual reconfiguration, driven by a dynamic milieu of heterogeneous processes. Postnatal brain plasticity is associated with increased vulnerability to environmental stimuli. However, little is known regarding the ontogeny and temporal manifestations of inter- and intra-regional functional connectivity that comprise functional brain networks. Resting-state functional magnetic resonance imaging (rs-fMRI) has emerged as a promising non-invasive neuroinvestigative tool, measuring spontaneous fluctuations in blood oxygen level dependent (BOLD) signal at rest that reflect baseline neuronal activity. Over the past decade, its application has expanded to infant populations providing unprecedented insight into functional organization of the developing brain, as well as early biomarkers of abnormal states. However, many methodological issues of rs-fMRI analysis need to be resolved prior to standardization of the technique to infant populations. As a primary goal, this methodological manuscript will (1) present a robust methodological protocol to extract and assess resting-state networks in early infancy using independent component analysis (ICA), such that investigators without previous knowledge in the field can implement the analysis and reliably obtain viable results consistent with previous literature; (2) review the current methodological challenges and ethical considerations associated with emerging field of infant rs-fMRI analysis; and (3) discuss the significance of rs-fMRI application in infants for future investigations of neurodevelopment in the context of early life stressors and pathological processes. The overarching goal is to catalyze efforts toward development of robust, infant-specific acquisition, and preprocessing pipelines, as well as promote greater transparency by researchers regarding methods used.

Rodent models have opened the door to a better understanding of the neurobiology of brain disorders and increased our ability to evaluate novel treatments. Resting-state functional magnetic resonance imaging (rs-fMRI) allows for in vivo exploration of large-scale brain networks with high spatial resolution. Its application in rodents affords researchers a powerful translational tool to directly assess/explore the effects of various pharmacological, lesion, and/or disease states on known neural circuits within highly controlled settings. Integration of animal and human research at the molecular-, systems-, and behavioral-levels using diverse neuroimaging techniques empowers more robust interrogations of abnormal/ pathological processes, critical for evolving our understanding of neuroscience. We present a comprehensive protocol to evaluate resting-state brain networks using Independent Component Analysis (ICA) in rodent model. Specifically, we begin with a brief review of the physiological basis for rs-fMRI technique and overview of rs-fMRI studies in rodents to date, following which we provide a robust step-by-step approach for rs-fMRI investigation including data collection, computational preprocessing, and brain network analysis. Pipelines are interwoven with underlying theory behind each step and summarized methodological considerations, such as alternative methods available and current consensus in the literature for optimal results. The presented protocol is designed in such a way that investigators without previous knowledge in the field can implement the analysis and obtain viable results that reliably detect significant differences in functional connectivity between experimental groups. Our goal is to empower researchers to implement rs-fMRI in their respective fields by incorporating technical considerations to date into a workable methodological framework.