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1. High-resolution awake mouse fMRI at 14 Tesla

   https://doi.org/10.1101/2023.12.08.570803  

   Hike, David; Liu, Xiaochen; Xie, Zeping; Zhang, Bei; Choi, Sangcheon; Zhou, Xiaoqing Alice; Liu, Andy; Murstein, Alyssa; Jiang, Yuanyuan; Devor, Anna; et al (December 2023, bioRxiv)

   Abstract High-resolution awake mouse fMRI remains challenging despite extensive efforts to address motion-induced artifacts and stress. This study introduces an implantable radiofrequency (RF) surface coil design that minimizes image distortion caused by the air/tissue interface of mouse brains while simultaneously serving as a headpost for fixation during scanning. Using a 14T scanner, high-resolution fMRI enabled brain-wide functional mapping of visual and vibrissa stimulation at 100x100x200µm resolution with a 2s per frame sampling rate. Besides activated ascending visual and vibrissa pathways, robust BOLD responses were detected in the anterior cingulate cortex upon visual stimulation and spread through the ventral retrosplenial area (VRA) with vibrissa air-puff stimulation, demonstrating higher-order sensory processing in association cortices of awake mice. In particular, the rapid hemodynamic responses in VRA upon vibrissa stimulation showed a strong correlation with the hippocampus, thalamus, and prefrontal cortical areas. Cross-correlation analysis with designated VRA responses revealed early positive BOLD signals at the contralateral barrel cortex (BC) occurring 2 seconds prior to the air-puff in awake mice with repetitive stimulation, which was not detectable with the randomized stimulation paradigm. This early BC activation indicated learned anticipation through the vibrissa system and association cortices in awake mice under continuous training of repetitive air-puff stimulation. This work establishes a high-resolution awake mouse fMRI platform, enabling brain-wide functional mapping of sensory signal processing in higher association cortical areas. Significance StatementThis awake mouse fMRI platform was developed by implementing an advanced implantable radiofrequency (RF) coil scheme, which simultaneously served as a headpost to secure the mouse head during scanning. The ultra-high spatial resolution (100x100x200µm) BOLD fMRI enabled the brain-wide mapping of activated visual and vibrissa systems during sensory stimulation in awake mice, including association cortices, e.g. anterior cingulate cortex and retrosplenial cortex, for high order sensory processing. Also, the activation of barrel cortex at 2 s prior to the air-puff indicated a learned anticipation of awake mice under continuous training of the repetitive vibrissa stimulation. 

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2. Laminar-specific functional connectivity mapping with multi-slice line-scanning fMRI

   https://doi.org/10.1093/cercor/bhab497  

   Choi, Sangcheon; Zeng, Hang; Chen, Yi; Sobczak, Filip; Qian, Chunqi; Yu, Xin (February 2022, Cerebral Cortex)

   Abstract 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. 

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3. Multimodal monitoring of human cortical organoids implanted in mice reveal functional connection with visual cortex

   https://doi.org/10.1038/s41467-022-35536-3  

   Wilson, Madison N.; Thunemann, Martin; Liu, Xin; Lu, Yichen; Puppo, Francesca; Adams, Jason W.; Kim, Jeong-Hoon; Ramezani, Mehrdad; Pizzo, Donald P.; Djurovic, Srdjan; et al (December 2022, Nature Communications)

   Abstract Human cortical organoids, three-dimensional neuronal cultures, are emerging as powerful tools to study brain development and dysfunction. However, whether organoids can functionally connect to a sensory network in vivo has yet to be demonstrated. Here, we combine transparent microelectrode arrays and two-photon imaging for longitudinal, multimodal monitoring of human cortical organoids transplanted into the retrosplenial cortex of adult mice. Two-photon imaging shows vascularization of the transplanted organoid. Visual stimuli evoke electrophysiological responses in the organoid, matching the responses from the surrounding cortex. Increases in multi-unit activity (MUA) and gamma power and phase locking of stimulus-evoked MUA with slow oscillations indicate functional integration between the organoid and the host brain. Immunostaining confirms the presence of human-mouse synapses. Implantation of transparent microelectrodes with organoids serves as a versatile in vivo platform for comprehensive evaluation of the development, maturation, and functional integration of human neuronal networks within the mouse brain. 

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4. High Spatiotemporal Resolution Radial Encoding Single‐Vessel fMRI

   https://doi.org/10.1002/advs.202309218  

   Jiang, Yuanyuan; Pais‐Roldán, Patricia; Pohmann, Rolf; Yu, Xin (April 2024, Advanced Science)

   Abstract High‐field preclinical functional MRI (fMRI) is enabled the high spatial resolution mapping of vessel‐specific hemodynamic responses, that is single‐vessel fMRI. In contrast to investigating the neuronal sources of the fMRI signal, single‐vessel fMRI focuses on elucidating its vascular origin, which can be readily implemented to identify vascular changes relevant to vascular dementia or cognitive impairment. However, the limited spatial and temporal resolution of fMRI is hindered hemodynamic mapping of intracortical microvessels. Here, the radial encoding MRI scheme is implemented to measure BOLD signals of individual vessels penetrating the rat somatosensory cortex. Radial encoding MRI is employed to map cortical activation with a focal field of view (FOV), allowing vessel‐specific functional mapping with 50 × 50 µm²in‐plane resolution at a 1 to 2 Hz sampling rate. Besides detecting refined hemodynamic responses of intracortical micro‐venules, the radial encoding‐based single‐vessel fMRI enables the distinction of fMRI signals from vessel and peri‐vessel voxels due to the different contribution of intravascular and extravascular effects. 

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5. Natural scene sampling reveals reliable coarse-scale orientation tuning in human V1

   https://doi.org/10.1038/s41467-022-34134-7  

   Roth, Zvi N.; Kay, Kendrick; Merriam, Elisha P. (December 2022, Nature Communications)

   Abstract Orientation selectivity in primate visual cortex is organized into cortical columns. Since cortical columns are at a finer spatial scale than the sampling resolution of standard BOLD fMRI measurements, analysis approaches have been proposed to peer past these spatial resolution limitations. It was recently found that these methods are predominantly sensitive to stimulus vignetting - a form of selectivity arising from an interaction of the oriented stimulus with the aperture edge. Beyond vignetting, it is not clear whether orientation-selective neural responses are detectable in BOLD measurements. Here, we leverage a dataset of visual cortical responses measured using high-field 7T fMRI. Fitting these responses using image-computable models, we compensate for vignetting and nonetheless find reliable tuning for orientation. Results further reveal a coarse-scale map of orientation preference that may constitute the neural basis for known perceptual anisotropies. These findings settle a long-standing debate in human neuroscience, and provide insights into functional organization principles of visual cortex. 

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