Keywords: Functional Connectivity, fMRI (resting state)

Motivation: Electroencephalography (EEG) and resting-state functional MRI (rs-fMRI) are both critical tools for investigating epilepsy, and their combination will further reveal  meaningful insights.

Goal(s): This study investigates the correlation between EEG spikes and functional connectivity in a drug-induced epileptic small-animal model.

Approach: An epileptic animal model was employed by injecting pentylenetetrazol (PTZ) through intraperitoneal to trigger acute epileptic-like abnormal neuron discharges, and EEG and rs-fMRI data were acquired seperately.

Results: This study integrated longitudinal rs-fMRI monitoring and EEG recordings in the same epilepsy animal model to assess drug-induced epileptic signals, showing and increase of both EEG spike numbers and C.C. after inducing epilepsy drug.

Impact: This study demonstrate the potential of brain region-to-region connectivity becoming a new bio marker of epilepsy diagnosis. However, greater precision and repeatablility of fMRI measurements is required for future studies to accurately align fMRI data with the electrophysiological data.

Keywords: Functional Connectivity, Parkinson's Disease, deep brain stimulation

Motivation: Addressing subthalamic nucleus deep brain stimulation (STN-DBS) limitations in Parkinson's Disease (PD), such as metabolic disorder and cognitive dysfunction. We explored nucleus accumbens deep brain stimulation (NAc-DBS) as an alternative, aiming to enhance motor, cognitive, and metabolic functions comprehensively.

Goal(s): Investigate NAc-DBS effectiveness, bridging STN-DBS gaps, enhancing motor skills, and improving cognitive and metabolic functions in PD.

Approach: Utilized behavioral tests, brain magnetic resonance imaging analysis, and bioenergetic analysis to evaluate NAc-DBS and STN-DBS impact on the MitoPark PD mouse model.

Results: NAc-DBS significantly enhanced cognitive, motor functions, and energy metabolism, offering a promising therapeutic solution for PD patients.

Impact: Our findings transform Parkinson's treatment, sheding a light to patients. The dual benefits of NAc-DBS inspire new inquiries, reshaping therapies with metabolic modulation. Improved outcomes redefine standards, offering hope for enhanced quality of life.

Keywords: Functional Connectivity, Brain

Motivation: The biophysical mechanisms underlying changes in functional connectivity upon stroke remain unclear. 

Goal(s): The present study aims at investigating how disrupting a specific and well-localized cortical area modulates spontaneous long-range functional connectivity. 

Approach: A novel approach based on intrinsic oscillatory modes exhibiting stationary wave pattern features was used to provide insight into the organizing principles underpinning spontaneous long-range FC.

Results: The presented intrinsic mode framework revealed global reorganization following local disruption with enhancement of corticostriatal activity in stroke. 

Impact: Our findings provide an important insight augur well for better understanding of neural network reorganization.

Keywords: fMRI Analysis, Metabolism, obesity diabetes

Motivation: Obesity and hyperglycemia would both affect brain function, while the longitudinal evolution of brain connectivity from obesity to diabetes is unknow.

Goal(s): Obesity and diabetes rat brain were evaluated to find the regions that were mostly affected by the diabetic incidence.

Approach: Rats were scanned at baseline and 10 days after streptozotocin injection (for diabetes model). Functional connectivity density (FCD) was applied to detect affected brain regions.

Results: Visual cortex’s FCD was increased in both obesity and diabetes. Diabetic rats show increased FCD in insular cortex and decreased FCD in ventral pallidum after streptozotocin injection, and these changes are correlated with fasting glycemia.

Impact: Obesity and diabetes show a progressive effect on cortex including visual and insular region. Acute changes are found in diabetic brain after streptozotocin injection for ventral pallidum, which suggested an impaired reward system in the development of T2DM.

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

Motivation: To evaluate whether changes in resting state functional connectivity within and between brain functional networks reveal the effects of an injury to motor cortex in squirrel monkey brain.

Goal(s): The goal was to quantify the connectivity changes within and between functionally relevant regions of a squirrel monkey brain post a motor cortex lesion. 

Approach: Resting state BOLD signals were acquired and analyzed by correlating functional MRI time courses from ICA detected networks using Pearson’s correlation.

Results: Differential changes in connectivity measures were observed both within and between functional networks post the lesion which indicates the usefulness of studying both the measures in conjunction. 

Impact: The study demonstrates the utility of within-network connectivity measures in conjunction with the traditional approach of  computing between-network connectivity to investigate the effects of a motor cortex injury. This has translational value in early diagnosis and treatment planning in patients. 

Keywords: Functional Connectivity, Brain

Motivation: To validate the derivation of functional networks from resting state and confirm the contribution of specific neuron types to BOLD responses.

Goal(s): Our aim is to compare resting state BOLD-derived functional networks with those from neuron-type selective optogenetic and natural tactile stimulationin the non-human primate brain.

Approach: We compared the BOLD signals in the brains of squirrel monkeys under three conditions: in response to blue light optogenetic stimulation, vibrotactile stimulation of fingers, and in a resting state.

Results: It shows the neural specificity of the optogenetic fMRI approach and its potential to enhance the understanding of brain circuits and connectivity within S2.

Impact: This study's validation of functional networks  from resting-state BOLD acquisitions and the confirmation of optogenetic fMRI's neural selectivity helps with the understanding brain function. These results encourage further investigations for deeper insights into neurological conditions.

Keywords: Functional Connectivity, Neuroscience

Motivation: The effects of passive hyperthermia on brain function in resting-state mice are unknown.

Goal(s): To expiore the rs-fMRI in hyperthermia treated and normal mice brain.

Approach: The ICA network and ROI-ROI FC in passive hyperthermia mice brain were compared with normal control.

Results: The ICA networks changed and the overall ROI-ROI FC of the passive hyperthermia mice decreased.

Impact: After prolonged exposure to high temperature has a greater impact on the overall perception and cognitive level of mice, which might help understand the relationship between neuronal activities and physiological thermal sensation and regulation as well as behavioral changes.

Keywords: Task/Intervention Based fMRI, fMRI (task based), Awake, fMRI, mouse, MB-SWIFT, ketamine, xylazine

Motivation: Anesthesia is a major confounding factor for pre-clinical fMRI and thus awake fMRI protocols with minimal body restraints are needed.

Goal(s): Our goal was to develop a novel motion-tolerant fMRI approach for awake mice and to compare sensory responsiveness between awake and anesthetized mice.

Approach: Following a 14-day habituation protocol, mice were imaged using zero-echo-time MB-SWIFT fMRI with visual and auditory stimulation schemes in awake state and under ketamine-xylazine anesthesia.

Results: In awake mice, the activation of all key nodes was detected after both sensory stimuli. However, anesthesia suppressed particularly the auditory responses and affected the fMRI response shapes.

Impact: Awake animal imaging has gained much popularity in recent preclinical studies. Together with quiet and motion-tolerant MB-SWIFT imaging our approach has potential for more complex behavioral fMRI designs that improve our understanding of neuroscience and support translational drug discovery.

Keywords: fMRI Acquisition, Brain, awake imaging, rodents, multi-center

Motivation: To bring awareness on the heterogeneity in awake rodent functional imaging. We aim to identify protocol differences that optimize awake functional connectivity, reproducibility and collaboration.

Goal(s): To aggregate awake rodent functional datasets, establish population parameters, provide evidence-based recommendations, compare functional Magnetic Resonance Imaging and functional Ultrasound, foster collaborations. 

Approach: We collect datasets from mice and rats, preprocess and run a seed-based analysis at the individual-level using RABIES. Group-level analysis is performed in Python, resulting in functional connectivity specificity maps.

Results: We have gathered 5 mice-datasets and 4 rat-datasets totaling 122 scans with great variability in rodent characteristics, imaging methods, and experimental designs.

Impact: Findings will empower researchers to refine awake rodent functional imaging, enhancing investigations into cognitive and behavioral processes, without the anesthesia confounds. This approach closely parallels human brain imaging, enhancing translational relevance and providing an accurate representation of conscious brain function.

Keywords: fMRI Acquisition, fMRI (resting state), Mice, Awake Imaging

Motivation: To increase the translatability of preclinical imaging data, awake protocols have to be developed.

Goal(s): Here we outline a protocol for awake task free fMRI using freely behaving head fixed mice. 

Approach: After headplate surgery and habituation to a holder containing a treadmill, mice are scanned up to 6 times. 

Results: The corticosterone and framewise displacement show that habituation seems to continue during scanning, suggesting that the habituation protocol needs to be lengthened. However, after dual regression analysis, activity within task free networks can be seen in the data, meaning that this protocol takes steps in the improvement of translatability of data.

Impact: To increase the translatability of functional MRI data, development of awake protocols is necessary. This allows for removal of the confound of anesthesia as well as opening up the option for behavioral paradigms during scanning.

Keywords: fMRI Acquisition, Brain, rats, multicenter, sensory-evoked, heterogeneity

Motivation: We address the need for standardization and collaboration in rat sensory-evoked fMRI by providing evidence-based recommendations and open-access datasets, fostering community growth.

Goal(s): We aim to assess inter- and intra-datasets variability, focusing on image acquisition and experimental protocols, and to optimize analysis by comparing hemodynamic response functions and denoising methods.

Approach: We collected 17 rat datasets from 10 centers, applied standardized preprocessing, and analyzed the sensory-evoked responses at individual and groups levels. Project code is openly available.

Results: Our study revealed significant diversity in rat attributes, anesthesia protocols, and imaging acquisition parameters across datasets. We are currently optimizing analyses to strengthen protocol robustness.

Impact: We present evidence for the substantial heterogeneity intra- and inter-datasets of rat sensory-evoked fMRI. We will provide guidelines to enhance reproducibility, facilitate cross-laboratory comparisons, collaborations in neuroimaging research, and encourage more robust findings with potential translational applications.

Keywords: Task/Intervention Based fMRI, fMRI, neurovascular coupling

Motivation: Previous study found brain-state dependent astrocytic calcium signals are related to positive and negative BOLD-fMRI signals. However, causal evidences regarding the contribution of astrocytes to BOLD signals is lacking.

Goal(s): We aimed to provide causal evidences for the bidirectional contribution of astrocytic calcium activity on BOLD-fMRI signals.

Approach: We applied simultaneous calcium imaging and awake mouse fMRI to detect distinct astrocytic signals (task-aligned vs. spontaneous) coupled to BOLD signals in three conditions, including no manipulation, activation and inhibition of S1BF astrocytes.

Results: We found whisker stimulation-evoked astrocyte activity mainly contributes to positive BOLD signals, while state-specific astrocyte activity contributes to negative BOLD signals.

Impact: We provide casual evidences that astrocytes bidirectionally regulated BOLD signals. Moreover, our results challenge the prevailing interpretation of the BOLD signal solely as an indicator of neuronal activity by highlighting the impact of arousal-specific involvement of astrocytes in neurovascular coupling.

Keywords: Task/Intervention Based fMRI, fMRI (task based), functional connectivity, acute post-surgical pain, sex difference, mechanosensation, dimensionality reduction, principal component analysis

Motivation: Acute postsurgical pain remains difficult to treat and may result in complications including chronic pain and increased use of opioids if insufficiently controlled. 

Goal(s): A better understanding of the mechanisms inducing and maintaining these pain states is critical in both sexes. 

Approach: Longitudinal task fMRI was performed with two different mechanical stimulations in male and female mice following acute incision pain (INC) compared to sham-treated animals. 

Results: Our mixed-method analysis approach identifies INC-regulated brain regions and highlights divergent mechanical pain processing in mice of both sexes.

Impact: Our mixed-method analysis approach integrating the general linear model analysis combined with principal component analysis and analysis of functional connectivity provides deep insights into CNS plasticity during incision-induced pain and provides detailed information on relevant brain regions and interaction patterns.

Keywords: Task/Intervention Based fMRI, fMRI (task based), Zero echo time, demyelination, remyelination

Motivation: The changes in responses to sensory stimuli during demyelination and remyelination could help quantify neuro-functional deficits in neurodegenerative disorders.

Goal(s): The goal of this study was to explore the capability of fMRI to detect changes in the functional response during both demyelination and remyelination.

Approach: A genetic mouse model of widespread demyelination and remyelination was imaged with MB-SWIFT fMRI during visual stimulation.

Results: We observed alterations in activation maps and fMRI responses to visual stimuli during demyelination. The function was restored during the remyelination phase.

Impact: We show that zero echo time MB-SWIFT fMRI protocol with visual stimulation can detect myelination-associated differences in neuro-functional responses in mice and thus lends itself as a potential translational biomarker for disease and treatment monitoring in drug development.

Keywords: fMRI Acquisition, Brain, DIANA, Steady-State

Motivation: Anatomical connectivity underlies brain function, but currently cannot be traced robustly in living animals.

Goal(s): We sought to understand how the structure and plasticity of neuronal projections contribute to functional relationships.

Approach: A genetic reporter for MRI was delivered using viral injections and visualization of the reporter was compared with histology, diffusion tractography, and resting state fMRI results.

Results: We validated the new tracing tool in mice, showed that some but not all projection strengths correlate with functional measures, and demonstrated that connection strength changes relate variably to functional connectivity changes in a longitudinal model of opioid exposure.

Impact: This work validates and applies a genetic reporter for fMRI that permits neuronal projections from viral injection sites to be visualized longitudinally with fidelity in individual animals. Our results help explain functional connectivity relationships in terms of circuit-level contributions.

Keywords: Task/Intervention Based fMRI, fMRI (task based), Excitation and Inhibition balance, Mouse fMRI, Autism

Motivation: The hyper- or hyporeactivity to sensory input is a common diagnostic criterion in autism, potentially influencing BOLD signals.

Goal(s): Our study was centered on unraveling the underlying mechanisms governing the positive and negative BOLD responses to low and high sensory stimulus frequencies. A ratio of BOLD responses of high frequency to low frequency may reflect E:I balance. 

Approach: Our study delved into BOLD responses during varied sensory stimulation frequencies

Results: We observed increased neural activity and BOLD responses at lower frequencies, contrasting with suppressed cortical activity and subsequent negative BOLD responses at higher frequencies.

Impact: A ratio of BOLD responses of high frequency to low frequency may reflect E:I balance, necessary for the clinical utility of BOLD fMRI to hyper- or hypo-reactivity responses to sensory inputs in autism