Keywords: Functional Connectivity, fMRI (resting state), functional connectivity, neuroscience, brain connectivity

Motivation: A current overarching challenge in neuroscience is to establish an integrated understanding of brain circuits and networks, particularly the interactions of neural populations across various spatiotemporal scales that give rise to functions and behavior. 

Goal(s): We posit that dissecting rsfMRI dynamics under direct single-pulse optogenetic modulation of thalamo-cortical networks will reveal critical insights into the functional architecture of rsfMRI networks. 

Approach: We deployed a computational approach (i.e., Gaussian PCA-HMM) to examine the organization of rsfMRI networks before and upon single-pulse stimulation of  thalamus. 

Results: We demonstrated a significant role of the basal forebrain and hypothalamus in regulating the transient dynamics of rsfMRI networks. 

Impact: The ability to directly perturb and model dynamics of rsfMRI networks present an unprecedented opportunity to understand brain-wide and higher-order circuits/networks, and their functions, which are difficult to probe using traditional behavioral and/or cognitive tasks and other neuroimaging approaches.

Keywords: Small Animals, Brain Connectivity, awake rodent imaging

Motivation: Most of rodent-fMRI is acquired under anesthesia, to minimize motion and stress. However, anesthesia hinders mouse-to-human translatability, since most of human fMRI is conducted whilst awake.

Goal(s): Here we aim to develop a biphasic protocol for conducting awake rodent-fMRI in mice and simultaneously recording mesoscopic calcium imaging data.

Approach: The animals undergo a first training and a refresher a few weeks later. Brain function is analyzed in simultaneous fMRI and mesoscopic calcium imaging measurements.

Results: Having a refresher training improves motion in the scanner. The two measures of brain function show interesting patterns over time, with partial agreement and some clear disagreement. 

Impact: Rodent-fMRI is typically done under anesthesia to minimize stress and motion. This limits mouse-human translatability (since humans are usually scanned awake). Here, we develop a biphasic approach to train mice to awake imaging, using simultaneous fMRI and Calcium imaging measures. 

Keywords: Functional Connectivity, Brain Connectivity

Motivation: This study aimed to create a reproducible coma animal model and develop neuroimaging techniques to illustrate underlying mechanisms during coma induction.

Goal(s): To investigate brain dynamic changes during coma induction and to identify the key regulatory brain regions involved in the process.

Approach: We induced a brainstem coma in rats, optimizing surgical procedures and utilizing multi-modal fMRI techniques. We recorded Glu signals and BOLD fMRI simultaneously during coma induction.

Results: The study revealed specific Glu-oscillations before coma induction and identified certain subcortical nuclei as potential key regulatory brain regions for inducing coma. These findings could enhance our understanding of coma-related brain state changes.

Impact: The optimized coma model and multi-modal imaging techniques in this study offer a deeper understanding of coma dynamics. The identification of specific regulatory brain regions and Glutamate oscillations may pave the way for improved clinical strategies and patient outcomes.

Keywords: Task/Intervention Based fMRI, fMRI (task based), awake, rat, multisensory

Motivation: Sensory research has typically focused on one system at a time, and basic mechanisms related to interactions between sensory systems remain poorly understood.

Goal(s): To detect and characterize brain-wide cross-sensory interplay, and to study how non-core circuits react to varying input into the core circuit.

Approach: Classical whisker pad stimulation in head-fixed awake and anesthetized rats in combination with a large number of fMRI measurements.

Results: We detected cross-sensory brain-wide activations to whisker pad stimulation. The activation profile of many non-core regions differed from that of the core circuit. Importantly, some features of cross-sensory interplay were not visible under anesthesia.

Impact: Cross-sensory activations are gaining increasing attention in imaging studies. Previously, multisensory interplay may have gone unnoticed, as the focus has been in the primary pathway. Our results also emphasize the importance of avoiding anesthesia in preclinical cross-sensory research.

Keywords: fMRI Acquisition, fMRI (task based), Auditory stimuli

Motivation: With improved scanning methods and SNR, auditory response studies in functional MRI require well-defined stimuli but are encumbered by the acoustic noise from the acquisition gradients and by the temporal inaccuracy of the external audio source.

Goal(s): Our goal was to use the acoustic noise generated by the MRI gradients to circumvent an external source for auditory fMRI.

Approach: We implemented BEBOP (BEeping BOld Pulse sequence) EPI which enables varying the echo spacing, and thus pitch,  per slice and per repetition and so provides a platform for auditory fMRI.

Results: An fMRI feasibility study at 7T was successfully implemented, measuring auditory-motor responses.

Impact: We demonstrated a new approach that simultaneously generates auditory stimuli and measures their BOLD response. The new approach offers high temporal accuracy of the auditory tasks due to the MRI gradients’ high temporal precision.

Keywords: fMRI Analysis, Data Analysis, Synchrony

Motivation: Fiber architecture-informed synchrony mapping (FAISM) has been proposed to capture task-evoked nonlinear brain activations, which involves image acquisitions of fMRI and high angular resolution diffusion image MRI (HARDI) with a long scan time and thus limits its applications.

Goal(s): The aim of this study is to modify the FAISM approach to mapping brain activation without time-consuming acquisitions of the HARDI data.

Approach: Hence, group-averaged fiber structures were used to replace the individual data to perform a fast FAISM.

Results: This approach demonstrates a high reproducibility at an individual level, which suggests that it can be used for reliable detections of nonlinear brain activation.

Impact: This approach is expected to serve as a standardized tool to measure neural activations with nonlinear hemodynamic responses.

Keywords: fMRI Acquisition, fMRI, Vessels, Vascular, Gray Matter, Oxygenation, fMRI (task based), fMRI Acquisition, fMRI Analysis, Hemodynamics

Motivation: Typical fMRI data observes hemodynamics from multiple vascular compartments in each voxel, however understanding the link between neuronal and vascular dynamics will require vessel-specific measurements.

Goal(s): To investigate the timing and amplitude of hemodynamic responses within individual arteries and veins of the human cortex and assess how they change with stimulus duration.

Approach: We applied single-vessel fMRI with multiple echoes to separate inflow and BOLD components, and distinguished intravascular and extravascular dynamics in and around arteries and veins.

Results: We observed faster dynamics in arteries, and a post-stimulus undershoot in all vessels, potentially providing new insights into hemodynamics in the human brain

Impact: Knowledge about hemodynamics within individual vascular compartment is provided by invasive microscopy in small-animal models, and less is known about hemodynamics in humans. Here we present vessel-specific measurements of hemodynamics in humans and reveal unexpected features in the fMRI response.

Keywords: fMRI Analysis, fMRI (resting state)

Motivation: Resting-state fMRI (rs-fMRI) based functional connectivity (fcMRI) is widely used to image neuronal networks, but it could be biased by the contribution of macrovasculature.

Goal(s): This study aims to provide a better understanding of vascular rs-fMRI contributions and their interpretation.

Approach: Our study evaluated macrovascular contributions to experimental rs-fcMRI data.

Results: We found both arteries and veins to substantially modulate fcMRI metrics. We also found that vascular-driven fcMRI spatial variance was disproportionately high given the low vascular voxel count. In particular, veins contribute more to connectivity strength than arteries, while arteries contribute more to spatial variance than veins.

Impact: The macrovasculature was previously shown to modulate functional connectivity and reduce its neuronal specificity, but a systematic analysis is still lacking. This study demonstrates macrovascular contributions at 3 Tesla and paves the way for the correction of bias in rs-fMRI.