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Abstract

Over the last decade, technological advances in the field of functional magnetic resonance imaging (fMRI) have made it possible to obtain localized measures of brain activity in real-time. This allows for applications such as online quality control of the acquisition, intra-operative fMRI, brain-computer-interfaces, and neurofeedback (NFB). Real-time fMRI (rt-fMRI) NFB studies have shown that a variety of different regions of interest (ROI) can be regulated in healthy and clinical populations, and by this, set the ground to become a potential non-invasive modulation. Moreover, other advances in the field of fMRI data analysis include functional connectivity, aiming to investigate interactions between distant brain regions. These studies have the potential to inform recent interest in the human brain “connectome.” Our work combines these two advances in the field of fMRI, and so we investigate the impact rt-fMRI NFB has on functional network organization, with the perspective of offering improved and more advanced neurofeedback. In our work, we focus on rt-fMRI NFB based on the auditory region as a single ROI, conducted with auditory stimuli on healthy subjects. In a series of papers, first, we report that subjects can downregulate activity of their right auditory cortex and that activity of the default mode network recovers via unique time courses in at least four of its components. Second, in the context of self-regulation, we utilized data-driven independent component analysis to reveal the auditory cortex as the main hub of functional connectivity changes, with changes also occurring in the brainstem, auditory pathway, and higher order areas involved in vision, attention, and working memory. Third, we utilized multivariate analyses and cross-validation to reveal 16 brain regions associated with self-regulation training. Subjects showed one of two distinct patterns of co-activation, suggesting that differences in connectivity may be related to differences in learning strategies. Finally, a meta-analysis based on several rt-fMRI NFB publications, had shown a large regulation network, including the anterior cingulate cortex, anterior insula, and the basal ganglia. This network could be involved in the underlying mechanism of self-regulation, and could improve future design of connectivity based rt-fMRI feedback. Our studies extend initial proof-of-concept studies indicating that subjects can self-regulate their own auditory cortex and go on to show that the impact of a single ROI regulation induces global network effects. In sum, we provide a comprehensive view of functional connectivity changes that occur throughout the brain with neurofeedback-based fMRI training. Those studies have the potential to advance the development of network-based rt-fMRI NFB for tinnitus clinical population, and also for other diseases that have network characteristics.

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