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Pupil dynamics presents varied correlation features with brain activity under different vigilant levels. The modulation of brain dynamic stages can arise from the lateral hypothalamus (LH), where diverse neuronal cell types contribute to arousal regulation in opposite directions via the anterior cingulate cortex (ACC). However, the relationship of the LH and pupil dynamics has seldom been investigated. Here, we performed local field potential (LFP) recordings at the LH and ACC, and whole-brain fMRI with simultaneous fiber photometry Ca2+ recording in the ACC, to evaluate their correlation with brain state-dependent pupil dynamics. Both LFP and functional magnetic resonance imaging (fMRI) data showed various correlations to pupil dynamics across trials that span negative, null, and positive correlation values, demonstrating brain state-dependent coupling features. Our results indicate that the correlation of pupil dynamics with ACC LFP and whole-brain fMRI signals depends on LH activity, suggesting a role of the latter in brain dynamic stage regulation., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows for comparisons with data modalities collected under invasive or terminal procedures. Currently, animal acquisitions are performed with varying protocols and analyses that hamper result comparison and integration. Here we introduce StandardRat, a consensus rat functional magnetic resonance imaging acquisition protocol tested across 20 centers. To develop this protocol with optimized acquisition and processing parameters, we initially aggregated 65 functional imaging datasets acquired from rats across 46 centers. We developed a reproducible pipeline for analyzing rat data acquired with diverse protocols and determined experimental and processing parameters associated with the robust detection of functional connectivity across centers. We show that the standardized protocol enhances biologically plausible functional connectivity patterns relative to previous acquisitions. The protocol and processing pipeline described here is openly shared with the neuroimaging community to promote interoperability and cooperation toward tackling the most important challenges in neuroscience., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Despite extensive studies detecting laminar functional magnetic resonance imaging (fMRI) signals to illustrate the canonical microcircuit, the spatiotemporal characteristics of laminar-specific information flow across cortical regions remain to be fully investigated in both evoked and resting conditions at different brain states. Here, we developed a multislice line-scanning fMRI (MS-LS) method to detect laminar fMRI signals in adjacent cortical regions with high spatial (50 μm) and temporal resolution (100 ms) in anesthetized rats. Across different trials, we detected either laminar-specific positive or negative blood-oxygen-level-dependent (BOLD) responses in the surrounding cortical region adjacent to the most activated cortex under the evoked condition. Specifically, in contrast to typical Layer (L) 4 correlation across different regions due to the thalamocortical projections for trials with positive BOLD, a strong correlation pattern specific in L2/3 was detected for trials with negative BOLD in adjacent regions, which indicated brain state-dependent laminar-fMRI responses based on corticocortical interaction. Also, in resting-state (rs-) fMRI study, robust lag time differences in L2/3, 4, and 5 across multiple cortices represented the low-frequency rs-fMRI signal propagation from caudal to rostral slices. In summary, our study provided a unique laminar fMRI mapping scheme to better characterize trial-specific intra- and inter-laminar functional connectivity in evoked and resting-state MS-LS., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Pupil dynamics serve as a physiological indicator of cognitive processes and arousal states of the brain across a diverse range of behavioral experiments. Pupil diameter changes reflect brain state fluctuations driven by neuromodulatory systems. Resting-state fMRI (rs-fMRI) has been used to identify global patterns of neuronal correlation with pupil diameter changes; however, the linkage between distinct brain state-dependent activation patterns of neuromodulatory nuclei with pupil dynamics remains to be explored. Here, we identified four clusters of trials with unique activity patterns related to pupil diameter changes in anesthetized rat brains. Going beyond the typical rs-fMRI correlation analysis with pupil dynamics, we decomposed spatiotemporal patterns of rs-fMRI with principal component analysis (PCA) and characterized the cluster-specific pupil-fMRI relationships by optimizing the PCA component weighting via decoding methods. This work shows that pupil dynamics are tightly coupled with different neuromodulatory centers in different trials, presenting a novel PCA-based decoding method to study the brain state-dependent pupil-fMRI relationship., Competing Interests: FS, PP, KT None, XY none, (© 2021, Sobczak et al.)

Resting-state functional MRI (rs-fMRI) studies have revealed specific low-frequency hemodynamic signal fluctuations (<0.1 Hz) in the brain, which could be related to neuronal oscillations through the neurovascular coupling mechanism. Given the vascular origin of the fMRI signal, it remains challenging to separate the neural correlates of global rs-fMRI signal fluctuations from other confounding sources. However, the slow-oscillation detected from individual vessels by single-vessel fMRI presents strong correlation to neural oscillations. Here, we use recurrent neural networks (RNNs) to predict the future temporal evolution of the rs-fMRI slow oscillation from both rodent and human brains. The RNNs trained with vessel-specific rs-fMRI signals encode the unique brain oscillatory dynamic feature, presenting more effective prediction than the conventional autoregressive model. This RNN-based predictive modeling of rs-fMRI datasets from the Human Connectome Project (HCP) reveals brain state-specific characteristics, demonstrating an inverse relationship between the global rs-fMRI signal fluctuation with the internal default-mode network (DMN) correlation. The RNN prediction method presents a unique data-driven encoding scheme to specify potential brain state differences based on the global fMRI signal fluctuation, but not solely dependent on the global variance., (© The Author(s) 2020. Published by Oxford University Press.)

Optogenetically driven manipulation of circuit-specific activity enables causality studies, but its global brain-wide effect is rarely reported. Here, we applied simultaneous functional magnetic resonance imaging (fMRI) and calcium recording with optogenetic activation of the corpus callosum (CC) connecting barrel cortices (BC). Robust positive BOLD was detected in the ipsilateral BC due to antidromic activity, spreading to the ipsilateral motor cortex (MC), and posterior thalamus (PO). In the orthodromic target, positive BOLD was reliably evoked by 2 Hz light pulses, whereas 40 Hz light pulses led to reduced calcium, indicative of CC-mediated inhibition. This presumed optogenetic CC-mediated inhibition was further elucidated by pairing light pulses with whisker stimulation at varied interstimulus intervals. Whisker-induced positive BOLD and calcium signals were reduced at intervals of 50/100 ms. The calcium-amplitude-modulation-based correlation with whole-brain fMRI signal revealed that the inhibitory effects spread to contralateral BC, ipsilateral MC, and PO. This work raises the need for fMRI to elucidate the brain-wide network activation in response to optogenetic stimulation., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Pupillometry, a noninvasive measure of arousal, complements human functional MRI (fMRI) to detect periods of variable cognitive processing and identify networks that relate to particular attentional states. Even under anesthesia, pupil dynamics correlate with brain-state fluctuations, and extended dilations mark the transition to more arousable states. However, cross-scale neuronal activation patterns are seldom linked to brain state-dependent pupil dynamics. Here, we complemented resting-state fMRI in rats with cortical calcium recording (GCaMP-mediated) and pupillometry to tackle the linkage between brain-state changes and neural dynamics across different scales. This multimodal platform allowed us to identify a global brain network that covaried with pupil size, which served to generate an index indicative of the brain-state fluctuation during anesthesia. Besides, a specific correlation pattern was detected in the brainstem, at a location consistent with noradrenergic cell group 5 (A5), which appeared to be dependent on the coupling between different frequencies of cortical activity, possibly further indicating particular brain-state dynamics. The multimodal fMRI combining concurrent calcium recordings and pupillometry enables tracking brain state-dependent pupil dynamics and identifying unique cross-scale neuronal dynamic patterns under anesthesia., Competing Interests: The authors declare no competing interest.

Extensive in vivo imaging studies investigate the hippocampal neural network function, mainly focusing on the dorsal CA1 region given its optical accessibility. Multi-modality fMRI with simultaneous hippocampal electrophysiological recording reveal broad cortical correlation patterns, but the detailed spatial hippocampal functional map remains lacking given the limited fMRI resolution. In particular, hemodynamic responses linked to specific neural activity are unclear at the single-vessel level across hippocampal vasculature, which hinders the deciphering of the hippocampal malfunction in animal models and the translation to critical neurovascular coupling (NVC) patterns for human fMRI. We simultaneously acquired optogenetically-driven neuronal Ca 2+ signals with single-vessel blood-oxygen-level-dependent (BOLD) and cerebral-blood-volume (CBV)-fMRI from individual venules and arterioles. Distinct spatiotemporal patterns of hippocampal hemodynamic responses were correlated to optogenetically evoked and spreading depression-like calcium events. The calcium event-related single-vessel hemodynamic modeling revealed significantly reduced NVC efficiency upon spreading depression-like (SDL) events, providing a direct measure of the NVC function at various hippocampal states.