Brain resting-state functional MRI connectivity: Morphological foundation and plasticity

Abstract

Despite the immense ongoing efforts to map brain functional connections and organizations with resting-state functional MRI (rsfMRI), the mechanisms governing the temporally coherent rsfMRI signals remain unclear. In particular, there is a lack of direct evidence regarding the morphological foundation and plasticity of these rsfMRI derived connections. In this study, we investigated the role of axonal projections in rsfMRI connectivity and its plasticity. Well-controlled rodent models of complete and posterior corpus callosotomy were longitudinally examined with rsfMRI at 7T in conjunction with intracortical EEG recording and functional MRI tracing of interhemispheric neuronal pathways by manganese (Mn(2+)). At post-callosotomy day 7, significantly decreased interhemispheric rsfMRI connectivity was observed in both groups in the specific cortical areas whose callosal connections were severed. At day 28, the disrupted connectivity was restored in the partial callosotomy group but not in the complete callosotomy group, likely due to the compensation that occurred through the remaining interhemispheric axonal pathways. This restoration - along with the increased intrahemispheric functional connectivity observed in both groups at day 28 - highlights the remarkable adaptation and plasticity in brain rsfMRI connections. These rsfMRI findings were paralleled by the intracortical EEG recording and Mn(2+) tracing results. Taken together, our experimental results directly demonstrate that axonal connections are the indispensable foundation for rsfMRI connectivity and that such functional connectivity can be plastic and dynamically reorganized atop the morphological connections.

Low-frequency hippocampal–cortical activity drives brain-wide resting-state functional MRI connectivity

“…Interhemispheric or homotopic rsfMRI connectivity networks are conserved across species (17,(68)(69)(70) and under distinct brain states (e.g., anesthesia, sleep, and wake) (71,72) and consistent among different human subjects (73). We (14,36) and others (16,17,68) have reliably measured interhemispheric rsfMRI connectivity in sensory cortices of rodents under light isoflurane (∼1.0%). However, the detection of more complex rsfMRI networks, such as default mode network, could be altered by anesthesia (74).…”

“…Resting-state functional MRI (rsfMRI) (11)(12)(13)(14) provides an invaluable, noninvasive imaging technique to map long-range, brain-wide functional connectivity networks based on the temporal coherence of infraslow (0.005-0.1 Hz) blood oxygen level dependent (BOLD) activity. The functional relevance of specific brain-wide networks in cognition can be inferred through rsfMRI connectivity.…”

Strategy‐based reasoning training modulates cortical thickness and resting‐state functional connectivity in adults with chronic traumatic brain injury

“…Second, changes in glial cells such as oligodendrocytes, astrocytes, and microglia (reviewed in Markham & Greenough, 2005 and Zatorre et al., 2012) may also reflect training‐induced changes in cortical thickness and rsFC. In particular, changes in oligodendrocytes, and subsequent myelination and myelin remodeling in the white matter are plausible candidate processes, as axonal connections are pivotal in the establishment of rsFC (Zhou et al., 2014). Further neuroimaging studies assessing white matter microstructure such as diffusion tensor imaging and myelin water imaging (Alonso‐Ortiz, Levesque, & Pike, 2015) may help to further clarify the validity of this hypothesis.…”

Long-range projections coordinate distributed brain-wide neural activity with a specific spatiotemporal profile

“…We performed optogenetic stimulation in lightly anesthetized rats (1% isoflurane). Blue light pulses at five frequencies (1 Hz: 10% pulse width duty cycle; 5, 10, 20, and 40 Hz: 30% duty cycle; light intensity: 40 mW/mm 2 ) were (1,5,10,20, and 40 Hz) were presented in a pseudorandomized order. All frequencies were presented at 30% duty cycle except for 1 Hz that was presented at 10% duty cycle.…”

“…Recent advances in structural (2,4) and functional connectivity (5)(6)(7)(8)(9)(10)(11)(12) mapping, as well as neural circuit modulatory tools, such as optogenetics (13,14), permit detailed, high-resolution neural examinations at unprecedented scales. In particular, functional connectivity mapping using resting-state functional MRI (rsfMRI) produces noninvasive visualization of slow and spontaneous hemodynamic fluctuations in humans (5-9) and animals (10)(11)(12). Coherent low-frequency (<1 Hz) fluctuations across functionally coupled, large-scale networks is an intriguing property, although the exact underlying neural bases and functional significance remain unclear.…”