Infraslow State Fluctuations Govern Spontaneous fMRI Network Dynamics

Abstract

Summary Spontaneous brain activity as assessed with resting-state fMRI exhibits rich spatiotemporal structure. However, the principles by which brain-wide patterns of spontaneous fMRI activity reconfigure and interact with each other remain unclear. We used a framewise clustering approach to map spatiotemporal dynamics of spontaneous fMRI activity with voxel resolution in the resting mouse brain. We show that brain-wide patterns of fMRI co-activation can be reliably mapped at the group and subject level, defining a restricted set of recurring brain states characterized by rich network structure. Importantly, we document that the identified fMRI states exhibit contrasting patterns of functional activity and coupled infraslow network dynamics, with each network state occurring at specific phases of global fMRI signal fluctuations. Finally, we show that autism-associated genetic alterations entail the engagement of atypical functional states and altered infraslow network dynamics. Our results reveal a novel set of fundamental principles guiding the spatiotemporal organization of resting-state fMRI activity and its disruption in brain disorders.

Network structure of the mouse brain connectome with voxel resolution

“…were resampled at a lower spatial resolution using an anatomical parcellation (Pearson's r, 0.59, 0.55, 0.54, p< 0.0001 for the DMN, LCN, and hippocampal network, respectively). This result is consistent with rsfMRI connectivity being a neural mass phenomenon reflecting the pooled activity of relatively large ensembles of neurons, exceeding the finer spatial scale of the voxel-wise mouse connectome [26][27][28] . Liska et al, 2015).…”

“…We however noted that the anatomical organization of the unimodal-polymodal gradient was anatomically consistent with dominant recurring patterns of fMRI co-activation (CAPs) recently described to govern spontaneous fMRI network dynamics in this species 26,43 . These take the form of infraslow oscillatory transitions in latero-cortical and midline poly-modal regions reminiscent of the topographical organization of gradient A.…”

“…It should be noted however that in the mouse the latter are known to exhibit a much lower degree of regional specialization than in primates, an observation that explains a categorization of latero-posterior visual and auditory territories as polymodal components of the posterior parietal cortex 55,56 . Importantly, our results also revealed that a dominant cortical gradient spatially shapes the emergence of prevailing patterns of cortical co-activation governing spontaneous fMRI dynamics, further relating the topography of the connectome with the structure and temporal evolution of spontaneous cortical activity 26 . The notion of a tight constraining effect of the structural connectome on functional network topography was further corroborated by evidence of largely overlapping functional and structural communities.…”

“…We additionally computed the correlation between SC gradients spatial maps and a dominant rsfMRI co-activation patterns (CAPS) published by 26 , in an attempt to establish a link between the organization of the structural connectome and FC dynamics. In their work, 26 described three pairs of recurring oscillatory states account for the more than 60% of rsfMRI variance.…”

Brain states govern the spatio-temporal dynamics of resting state functional connectivity

“…Several studies have demonstrated that the functional state of the brain is dynamic over time, and this is reflected in functional connectivity changes 72,73 . These dynamic states are quantifiable, depend on the ongoing infraslow activity and seem to show atypical dynamics in some neurological disorders as autism 74 . Degrees of wakefulness seem to play an important role in global functional connectivity 75 .…”