Biophysical and neural basis of resting state functional connectivity: Evidence from non-human primates

Abstract

Functional MRI has evolved from simple observations of regional changes in MRI signals caused by cortical activity induced by a task or stimulus, to the development of task-free acquisitions of time series of images in a resting state. Such resting state signals contain low frequency fluctuations which may be correlated between voxels, and strongly correlated regions are deemed to reflect functional connectivity within synchronized circuits. Resting state functional connectivity (rsFC) measures have been widely adopted by the neuroscience community, and are being used and interpreted as indicators of intrinsic neural circuits and their functional states in a broad range of applications, both basic and clinical. However, there has been relatively little work reported that validates whether inter-regional correlations in resting state fluctuations of MRI (rsfMRI) signals actually measure functional connectivity between brain regions, or to establish how MRI data correlate with other metrics of functional connectivity. In this mini-review, we summarize recent studies of rsFC within mesoscopic scale cortical networks (100μm – 10mm) within a well defined functional region of primary somatosensory cortex (S1), as well as spinal cord and brain white matter in non-human primates, in which we have measured spatial patterns of resting state correlations and validated their interpretation with electrophysiological signals and anatomic connections. Moreover, we emphasize that low frequency correlations are a general feature of neural systems, as evidenced by their presence in spinal cord as well as white matter. These studies demonstrate the valuable role of high field MRI and invasive measurements in an animal model to inform the interpretation of human imaging studies.

Neuromodulation of sensory networks in monkey brain by focused ultrasound with MRI guidance and detection

“…We used 8 Hz vibrotactile stimuli because it is a subtle and natural cutaneous stimulus that elicits robust touch sensation in humans and activates many cortical and subcortical brain regions, including S1 and S2 in the non-human primate 27 , 28 , 33 – 35 . We have previously demonstrated that many of the areas responding to such a stimulus are detectable as fMRI activations at ultra-high field (9.4 T) in the brains of squirrel monkeys under light anesthesia 30 , 31 and also show correlated signal variations in a resting state, reflecting their functional connectivity 36 , 37 . Extending our previous observations in squirrel monkeys, Fig.…”

Intrinsic functional architecture of the non-human primate spinal cord derived from fMRI and electrophysiology

“…While spinal electrophysiology has previously been performed in other animal models, the functional architecture and neural circuits of the central nervous system in NHPs share much greater similarities with those in humans. Previous reports have made use of NHPs to compare and understand the underlying biophysical basis of BOLD signals, but these were restricted to different cortices of the brain 37 . In this study, we have used NHPs to perform direct validation of MRI findings in the spinal cord using multichannel microelectrodes.…”

On the Relationship between MRI and Local Field Potential Measurements of Spatial and Temporal Variations in Functional Connectivity

“…Analgesic (buprenorphine) is for 3 days post-surgery. Detailed procedures have been described in our previous publication 12,53–55 . All experimental procedures were in compliance with and approved by the Institutional Animal Care and Use Committee of Vanderbilt University, and followed the guidelines of the National Institute of Health Guide for the care and use of laboratory animals.…”