Ruiliang Bai^1,2, Craig Stewart³, Dietmar Plenz³, and Peter J Basser^1
1Section on Quantitative Imaging and Tissue Science, DIBGI, NICHD, National Institutes of Health, Bethesda, MD, United States, ²Biophysics Program, Institute for Physical Science and Technology, University of Maryland, College Park, MD, United States, ³Section on Critical Brain Dynamics, LSN, NIMH, National Institutes of Health, Bethesda, MD, United States

Diffusion MRI has been proposed as a noninvasive neuroimaging method to detect neuronal activity more directly than BOLD fMRI, yet, initial findings have proven difficult to interpret and reproduce. Here, we study the possible relationship between water diffusion and neuronal activity by simultaneous intracellular calcium fluorescence imaging and diffusion MR of organotypic rat brain cortex cultures. Although we found that diffusion MR can follow pathological changes during hyperexcitability, e.g., as those seen in epilepsy or during anoxia, it does not appear to be sensitive or specific enough to detect or follow normal neuronal activity.

Tomokazu Tsurugizawa¹, Yoshifumi Abe¹, and Denis Le Bihan^1
1NeuroSpin, Bât 145, Commissariat à l’Energie Atomique-Saclay Center, 91191, France, Gif-sur-Yvette, France

BOLD fMRI which relies on neurovascular coupling may fail when neurovascular coupling is weakened, such as anesthesia or alcohol intoxication. In contrast, diffusion fMRI has been shown to be more directly linked to neuronal activation even in the absence of neurovascular coupling. We compared BOLD fMRI and diffusion fMRI (ADC) time-courses with local field potentials (LFPs) in rat nucleus accumbens following alcohol stimulation under two different doses of medetomidine anesthesia. The ADC responses were correlated with LFP signals while BOLD signals were not. These results show the interest of diffusion fMRI to avoid confounds from varying conditions of neurovascular coupling.

Laurentius Huber¹, Sean Marrett¹, Daniel A Handwerker¹, Adam Thomas¹, Benjamin Gutierrez¹, Dimo Ivanov², Benedikt A Poser², and Peter A Bandettini^1
1Section of Functional Imaging Methods, National Institute of Mental Health, Bethesda, MD, United States, ²MBIC, Maastricht University, Maastricht, Netherlands

We present a fast new method for obtaining quantitative T₁ maps with high spatial (1 mm) and temporal resolutions (3 s). This method can be useful to investigate morphological dynamics of brain GM, e.g. during brain activity changes, plasticity changes, or pathology. The robustness of the developed method is demonstrated with a finger tapping fMRI experiment. We report a functional GM T₁increase of up to 100 ms, and a GM thickness increase by up to 0.25 mm.

Zhongwei Chen^1,2, Rong Xue¹, Jing An³, Kaibao Sun^1,2, Zhentao Zuo¹, Peng Zhang¹, and Danny JJ Wang^4
1State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China, People's Republic of, ²Graduate School, University of Chinese Academy of Sciences, Beijing, China, People's Republic of, ³Siemens Shenzhen Magnetic Resonance Ltd, Shenzhen, China, People's Republic of, ⁴Laboratory of FMRI Technology (LOFT), Department of Neurology, University of California Los Angeles, Los Angeles, CA, United States

Multi-phase passband steady state free precession (SSFP) cine fMRI can achieve a spatial resolution of a few mm3 and a temporal sampling rate of 50ms at 7 Tesla , while maintaining low geometric distortion and signal dropout. In this study, the feasibility and accuracy of the technique are demonstrated by two visual event-related functional MRI experiments.

Joana Alves Loureiro^1,2, Gisela Hagberg¹, Thomas Ethofer², Michael Erb², Klaus Scheffler¹, and Marc Himmelbach^3
1High-Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Tuebingen, Germany, ²BMMR, University Hospital Tuebingen, Tuebingen, Germany, ³Division of Neuropsychology, Centre for neurology, Tuebingen, Germany

The superior colliculus (SC) is a layered structure involved in visual and multisensory control. Due to its small size and location it is challenging to evaluate its function with the conventional MR fields.  In this study we compare the depth-dependence of visual signals in SC for 9.4T and 3T data. The highest signal was observed in the superficial zone of the superior colliculus (for both datasets). However, the increase in sensitivity  in the blood oxygen level dependent size allowed us to get higher response lateralization and a significative higher depth-dependence of visual signals in the 9.4T.

Yun Wang¹, Jennifer Robinson^1,2,3, and Gopikrishna Deshpande^1,2,3
1AU MRI Research Center, Department of Electrical and Computer Engineering, Auburn University, Auburn, AL, United States, ²Department of Psychology, Auburn University, Auburn, AL, United States,³Alabama Advanced Imaging Consortium,Auburn University and University of Alabama Birmingham, Birmingham, AL, United States

We investigated whether resting-state functional connectivity (FC) is sensitive to cortical layer-specific connectional differences using high resolution resting-state fMRI data obtained from healthy humans at 7T. Based on rat tracing studies, we hypothesized that FC between the thalamus and cortical layer I must be significantly greater than between the thalamus and other layers. Our results support this hypothesis. Further, there were no global connectivity differences between layers, ruling out artifactual influences from vasculature. This also opens the future possibility of microscopic investigations of the brain connectome using ultra-high field fMRI and will likely move the field away from blobology. 

Irati Markuerkiaga¹ and David G. Norris^1
1Donders Institute, Nijmegen, Netherlands

The specificity of GE-BOLD profiles is suspected to be degraded by intracortical veins. In this work  experimentally obtained GE-BOLD profiles for different subjects are deconvolved with a laminar point spread functions obtained from a model of cortical vasculature. The obtained underlying activation profiles are closer to the activity profiles expected  from electrophysiology for the type of stimulus used.

Tung-Lin Wu^1,2, Feng Wang^1,3, Li Min Chen^1,3, Adam W. Anderson^1,2,3, Zhaohua Ding^1,3, and John C. Gore^1,2,3
1Vanderbilt University Institute of Imaging Science, Nashville, TN, United States, ²Biomedical Engineering, Vanderbilt University, Nashville, TN, United States, ³Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States

We previously reported the first evidence of anisotropic rsfMRI-BOLD signals in white matter which appear to reflect a functional structure not previously detected. To prove these signals have a functional basis, we performed imaging of live squirrel monkeys under different baselines of neural activity by altering anesthesia levels. Specifically, we compared how different anesthesia levels modulate fractional power and spatio-temporal correlation tensors in white matter. Our results demonstrate that low frequency BOLD signal fluctuations behave similarly in grey and white matter. This indicates that anisotropic rsfMRI-BOLD signals in white matter encode neural activity. 

Jeroen C.W. Siero¹, Jill B. de Vis¹, and Jeroen Hendrikse^1
1Radiology, University Medical Center Utrecht, Utrecht, Netherlands

Slow fluctuating (< 0.1 Hz) BOLD signals during baseline conditions or ‘resting-state’ have seen interest in numerous studies, both in healthy and disease. Here we investigate cerebral vascular reactivity and baseline cerebral blood volume contributions to the slow fluctuating baseline BOLD signal.

Li-Ming Hsu¹, Gu Hong¹, Hanbing Lu¹, Elisabeth C. Caparelli¹, Elliot A. Stein¹, and Yihong Yang^1
1Neuroimaging Research Branch, National institute on drug abuse, Baltimore, MD, United States

Intrinsic brain networks seen in humans, including the default-mode network (DMN), have been demonstrated in non-human primates and rodents using resting-state functional fMRI (rs-fMRI). Characteristics of these brain networks, such as frequency specificity, have been assessed in humans, but are much less known in animal models. These characteristics are of importance when translating findings from preclinical models to clinical applications. The frequency range used in a human rs-fMRI analysis is typically ≤ 0.1 Hz; however, an appropriate frequency range in rodents remains unclear. In this study, we investigated the resting-state functional connectivity (rsFC) of rat brains in three frequency ranges: 1) 0.01 – 0.1 Hz, 2) 0.1 – 0.25 Hz, and 3) 0.25 – 0.5 Hz, and compared the result with that in human brains. 

Maryam Falahpour¹, Chi Wah Wong¹, and Thomas T. Liu^1
1Center for Functional Magnetic Resonance Imaging, University of California San Diego, San Diego, CA, United States

Global signal (GS) regression is a commonly used preprocessing approach in the analysis of resting-state fMRI data. However GSR should be used with caution as it can not only induce spurious anti-correlations, but may also remove signal of neural origin. Here we used simultaneously acquired EEG/fMRI data to study the relation between the GS and an EEG-based measure of vigilance at rest. We found that there is a significant negative correlation between the GS and EEG vigilance. Our results indicate that GS has a significant neuronal component and further emphasizes the need to exercise caution when regressing out the GS.

Amir Omidvarnia¹, David Vaughan^1,2, Mangor Pedersen¹, Mira Semmelroch¹, David Abbott¹, and Graeme Jackson^1,2,3
1Epilepsy Imaging, The Florey Institute of Neuroscience and Mental Health, Melbourne, Australia, ²Department of Neurology, Austin Health, Melbourne, Australia, ³Department of Medicine, The University of Melbourne, Melbourne, Australia

In this study, we aimed at developing an objective method for detecting clinically suspected epileptic networks through possible association between interictal EEG discharges and dynamic local fMRI connectivity in focal epilepsy. We designed a time-frequency framework for analysis of wavelet coherence between scalp EEG band amplitude fluctuations (BAFs) and dynamic regional phase synchrony (DRePS) of task-free fMRI in seven patients. The proposed method reveals nonstationary relationship between scalp interictal epileptic discharges (IEDs) and DRePS within ultra-slow frequencies (~0.003 – 0.03Hz). Evaluation of dynamic fMRI phase synchrony at rest, particularly using data-fusion with interictal scalp EEG, may provide useful markers of localized and transient brain connectivity disturbance in epilepsy.

Leon C. Ho^1,2, Russell W. Chan^1,2, Patrick P. Gao^1,2, Alex T.L. Leong^1,2, Celia M. Dong^1,2, and Ed X. Wu^1,2
1Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Hong Kong, China, People's Republic of, ²Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong, China, People's Republic of

Visual inputs are primarily processed by the visual system. However visual input also interacts with other sensory cortices to speed up or improve sensory perception. While the effect of different parameters of visual input to crossmodal influences remains largely unexplored, this study showed strong low frequency light evoked responses in auditory cortex, secondary somatosensory cortex, cingulate cortex and caudate putamen. The activations in those brain regions likely propagated from the visual cortex and influenced subcortical responses. Our current study provides a functional understanding to cortical crossmodal processing and its influences to subcortex upon visual stimuli of different intensities and frequencies. 

Jo-Fu Lotus Lin¹, Jonathan R Polimeni², Wen-Jui Kuo³, and Fa-Hsuan Lin^1
1Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan, ²Athinoula A. Martinos Center, Department of Radiology, Harvard Medical School, Massachusetts General Hospital, Charlestown, MA, United States, ³Institute of Neuroscience, National Yang Ming University, Taipei, Taiwan

We used inverse imaging to spatiotemporally characterize the relative latency and variability of the BOLD signal at human visual cortex with 0.1 s precision. The relative BOLD latency in the left and right visual cortex was 0.12 (s) +/- 0.33 (s). The BOLD variability in the left and right visual cortex was 0.39 (s) +/- 0.25 (s). Local relative BOLD latency was linearly related to local BOLD variability. The least variability (< 0.2 s) and the earliest onset of the BOLD signal were found at the trough of the calcarine sulcus.

Andrea Duggento¹, Luca Passamonti^2,3, Maria Guerrisi¹, and Nicola Toschi^1,4
1Department of biomedicine and prevention, University of Rome "Tor Vergata", Rome, Italy, ²Institute of Bioimaging and Molecular Physiology, National Research Council, Catanzaro, Italy, ³Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom, ⁴Department of Radiology, Martinos Center for Biomedical Imaging and Harvard Medical School, Boston, MA, United States

Reconstructing the direction of information flow ("causality") is crucial when studying evidence-based network models of the brain. We use multivariate analysis to develop a conditioning approach which measures the true directed coupling between two signals which are also indirectly connected through a large number of additional interdependent sources. After validation through synthetics noisy oscillator networks, we study data from 100 HCP subjects, revealing a clear-cut, sparse resting-state directed network structure and providing first-time evidence of a concerted directional interaction between subnetworks of the brain, with the salience network performing top-down integration of sensory-motor and cognitive processes.