Odor information is transmitted from the olfactory bulb to several primary olfactory cortical regions in parallel, including the anterior olfactory nucleus (AON) and piriform cortex (Pir). However, the specific roles of the olfactory bulb and cortical outputs in wider interactions with other interconnected regions throughout the brain remain unclear due to the lack of suitable in vivo techniques. Furthermore, emerging associations between olfactory-related dysfunctions and neurological disorders underscore the need for examining olfactory networks at the systems level. Using optogenetics, fMRI, and computational modeling, we interrogated the spatiotemporal properties of brain-wide neural interactions in olfactory networks. We observed distinct downstream recruitment patterns. Specifically, stimulation of excitatory projection neurons in OB predominantly activates primary olfactory network regions, while stimulation of OB afferents in AON and Pir primarily orthodromically activates hippocampal/striatal and limbic networks, respectively. Temporally, repeated OB or AON stimulation diminishes neural activity propagation brain-wide in contrast to Pir stimulation. Dynamic causal modeling analysis reveals a robust inhibitory effect of AON outputs on striatal and limbic network regions. In addition, experiments in aged rat models show decreased brain-wide activation following OB stimulation, particularly in the primary olfactory and limbic networks. Modeling analysis identifies a dysfunctional AON to Pir connection, indicating the impairment of this primary olfactory cortical circuit that disrupts the downstream long-range propagation. Our study delineates the spatiotemporal properties of olfactory neural activity propagation in brain-wide networks for the first time and distinguishes the roles of primary olfactory cortical, AON and Pir, outputs in shaping neural interactions at the systems level.

Thalamic reticular nucleus (TRN) has been shown to gate sensory thalamo-cortical interactions and selectively modulate thalamic sensory information processing according to behavioral demands. However, whether TRN can exert long-range, i.e., beyond thalamus, cross-modal modulation of sensory processing remains unclear. In this fMRI study, we demonstrate that optogenetic excitation of somatosensory-specific TRN enhances cross-modal excitatory sensory inputs but suppresses cross-modal competing inputs at somatosensory cortices. Our work provides insight into how TRN differentially gate the processing of distinct cross-modal sensory information at large-scale, which may be critical for ensuring the balance between various task demands.

Purpose To provide a complex-valued deep learning approach for partial Fourier (PF) reconstruction of complex MR images. Methods Conventional PF reconstruction methods, such as projection onto convex sets (POCS), uses low-resolution image phase information from the central symmetrically sampled k-space for image reconstruction. However, this smooth phase constraint undermines the phase estimation accuracy in presence of rapid local phase variations, causing image artifacts and limiting the extent of PF reconstruction. Using both magnitude and phase characteristics in big complex image datasets, we propose a complex-valued deep learning approach with an unrolled network architecture for PF reconstruction that iteratively reconstructs PF sampled data and enforces data consistency. We evaluate our approach for reconstructing both spin-echo and gradient-echo data. Results The proposed method outperformed the iterative POCS PF reconstruction method. It produced better artifact suppression and recovery of both image magnitude and phase details in presence of local phase changes. No noise amplification was observed even for highly PF reconstruction. Moreover, the network trained on axial brain data could reconstruct sagittal and coronal brain and knee data. This method could be extended to 2D PF reconstruction and joint multi-slice PF reconstruction. Conclusion Our proposed method can effectively reconstruct MR data even at low PF fractions, yielding high-fidelity magnitude and phase images. It presents a valuable alternative to conventional PF reconstruction, especially for phase-sensitive 2D or 3D MRI applications.

Motivation: Despite the enormous potential inherent in rsfMRI, the neural basis underlying rsfMRI connectivity remains unclear. Goal(s): We aim to dissect the role of the TRN inhibitory neural population in rsfMRI connectivity given its prominent role in maintaining/regulating thalamo-cortical oscillations. Approach: We examined brain-wide activity and rsfMRI connectivity changes after optogenetically manipulating neural activity in rodent TRN. Results: We demonstrate that somatosensory-specific TRN inhibitory networks play a role in modulating rsfMRI connectivity of sensorimotor and default mode networks. Impact: Present studies examining neural basis of rsfMRI have primarily focused on excitatory networks. Here, we investigated the role of a major inhibitory thalamic nucleus to advance our understanding of the contributions of inhibitory inputs in regulating brain-wide rsfMRI networks.

In the recent decade, resting-state functional MRI (rsfMRI) has emerged as the most invaluable, non-invasive imaging technique to map long-range, brain-wide functional connectivity networks. Despite the enormous potential inherent in this technique, our present knowledge of the neural underpinnings of rsfMRI connectivity remains generally incomplete given the lack of studies examining the role of the inhibitory neural population, which is the counterpart of the excitatory neurons. In this study, we directly examine the role of zona incerta, which is one of the major source of inhibitory drive to the cortex.

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.

Olfactory adaptation due to repeated odor cues has been studied extensively by fMRI or electrophysiology studies in several primary olfactory regions (i.e., anterior olfactory nucleus, AON, and piriform cortex, Pir). However, the modulatory role of other primary olfactory regions (e.g., amygdala and entorhinal cortex) and their integrations with high-order olfactory regions during olfactory adaptation is likely underestimated due to the documented weak and unstable responses at regions beyond AON and Pir with conventional presentation of odor stimuli. Here, we deployed an optogenetic fMRI approach to improve sensitivity in detecting olfactory responses and examine their adaptation at the systems level.

The dorsal lateral geniculate nucleus (dLGN) plays an essential role in visual processing. There are two types of topographically segregated excitatory neurons in dLGN with different outputs to visual cortex, suggesting functional differences when processing visual inputs at the subcortical thalamic level. However, their long-range functional pathways have yet to be reported. Here, we employed optogenetics in combination with fMRI to precisely target the two subdivisions of dLGN and examine whether these two types of neurons are truly functionally diverse at the systems level to facilitate various known complex visual processing functions.

Motivation: We do not yet know where zona incerta (ZI) neural activity is distributed in central pathways despite extensive knowledge of incertal projections and functions. Goal(s): We aim to reveal the long-range functional pathways of ZI neural activity to bridge the knowledge gap between known anatomical projections and implicated functions. Approach: We deployed optogenetic fMRI to directly initiate neural activity at ZI and computational approaches to characterize the downstream central pathways involved. Results: The propagation of neural activity from ZI are not restricted to monosynaptic projections within known subcortical structures, but along multi-synaptic, long-range central pathways. Impact: Characterization of ZI functional pathways is of tremendous value to neuroscientists and clinicians for future in-depth investigations of key/previously undefined incertal regions and for designing more effective therapeutic measures such as deep brain stimulation, where ZI is a key target.

The olfactory system plays a pivotal role in driving behavioral responses that are critical to survival. In particular, the decline in ability to detect and discriminate odors in aged humans lead to an overall decrease in quality of life. However, our present understanding of olfactory dysfunction in aging brains beyond the cellular and micro-circuit level is scarce and incomplete. In this study, we deployed optogenetic fMRI to reveal the changes of brain-wide odor-associated regions brought about by aging in an accelerated aging rat model. We found diminished activations brain-wide indicating dysfunction at the systems level across multiple long-range olfactory pathways.

Motivation: rsfMRI network dynamics are essential for cognitive processes, however, their underlying neural bases remain unclear. Goal(s): Here, we aim to examine the neural oscillatory events underlying the dynamic patterns of rsfMRI networks across the entire brain. Approach: We employed simultaneous EEG-fMRI to record brain-wide rsfMRI and neural signals at default mode network. Further, EEG events were identified and temporally matched with dynamic rsfMRI network states derived from a data-driven model. Results: Our results demonstrated robust associations between rsfMRI network dynamics and neural oscillatory events, especially slow oscillation-coupled spindle, gamma events and slow oscillation. Impact: Our results demonstrated the different effects of spontaneous neural oscillatory events (e.g., slow oscillation, spindle, and gamma) in default mode network underlying the dynamics of rsfMRI networks.

Short single pulse stimulation is advantageous to map the downstream neural targets compared to pulse train stimulation because it can minimize the excessive neural synchronization and avoid numerous series of complex neural events. It is desirable for fMRI studies to investigate the properties of neural circuits via delivering single pulse stimulation. However, the subtle BOLD responses evoked by short stimuli are hard to detect due to the sensitivity issue. Here, we employed fMRI to examine the long-range downstream targets of the somatosensory thalamus with 10ms single pulse stimulation. A model-free fMRI analysis was utilized to visualize the spatiotemporal activity propagation.

The anterior olfactory nucleus (AON) and the piriform cortex (Pir) are the two primary sensory cortices critical for olfaction. Although it is well documented that both cortices overlap significantly in their functions in olfactory processing, molecular and anatomical tracing studies have indicated otherwise. Consequently, our present understanding of the functions of AON and Pir in olfactory processing at the systems level remains incomplete. In this study, we employed optogenetic fMRI to interrogate the role of AON and Pir in processing olfactory inputs and beyond, and the associated long-range olfactory pathways and their spatiotemporal response properties.