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ABSTRACT: Although resting-state brain activity has been demonstrated to correspond with task-evoked brain activation, the relationship between intrinsic and evoked brain activity has not been fully characterized. For example, it is unclear whether intrinsic activity can also predict task-evoked deactivation and whether the rest-task relationship is dependent on task load. In this study, we addressed these issues on 40 healthy control subjects using resting-state and task-driven [N-back working memory (WM) task] functional magnetic resonance imaging data collected in the same session. Using amplitude of low-frequency fluctuation (ALFF) as an index of intrinsic resting-state activity, we found that ALFF in the middle frontal gyrus and inferior/superior parietal lobules was positively correlated with WM task-evoked activation, while ALFF in the medial prefrontal cortex, posterior cingulate cortex, superior frontal gyrus, superior temporal gyrus, and fusiform gyrus was negatively correlated with WM task-evoked deactivation. Further, the relationship between the intrinsic resting-state activity and task-evoked activation in lateral/superior frontal gyri, inferior/superior parietal lobules, superior temporal gyrus, and midline regions was stronger at higher WM task loads. In addition, both resting-state activity and the task-evoked activation in the superior parietal lobule/precuneus were significantly correlated with the WM task behavioral performance, explaining similar portions of intersubject performance variance. Together, these findings suggest that intrinsic resting-state activity facilitates or is permissive of specific brain circuit engagement to perform a cognitive task, and that resting activity can predict subsequent task-evoked brain responses and behavioral performance. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
Human Brain Mapping 06/2012; · 5.88 Impact Factor
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ABSTRACT: Multimodal magnetic resonance imaging (MRI) techniques have been developed to noninvasively measure structural, metabolic, hemodynamic and functional changes of the brain. These advantages have made MRI an important tool to investigate neurodegenerative disorders, including diagnosis, disease progression monitoring, and treatment efficacy evaluation. This paper discusses recent findings of the multimodal MRI in the context of surrogate biomarkers for identifying the risk for AD in normal cognitive (NC) adults, brain anatomical and functional alterations in amnestic mild cognitive impairment (aMCI), and Alzheimer's disease (AD) patients. Further developments of these techniques and the establishment of promising neuroimaging biomarkers will enhance our ability to diagnose aMCI and AD in their early stages and improve the assessment of therapeutic efficacy in these diseases in future clinical trials.
Neurology research international. 01/2012; 2012:907409.
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ABSTRACT: Blood inflow from the upstream has contribution or contamination to the blood oxygen level-dependent (BOLD) functional signal both in its magnitude and time courses. During neuronal activations, regional blood flow velocity increases which results in increased fMRI signals near the macrovasculatures. The inflow effects are dependent on RF pulse history, slice geometry, flow velocity, blood relaxation times and imaging parameters. In general, the effect is stronger with more T(1) weighting in the signal, e.g. by using a short repetition time and a large flip angle. This article reviews the basic principle of the inflow effects, its appearances in conventional GRE, fast spin-echo (FSE) and echo-planar imaging (EPI) acquisitions, methods for separating the inflow from the BOLD effect as well as the interplay between imaging parameters and other physiological factors with the inflow effects in fMRI. Based on theoretical derivation and human experiments, the inflow effects have been shown to contribute significantly in conventional GRE but negligible in FSE acquisitions. For gradient-echo EPI experiments, the blood inflow could modulate both amplitude and the temporal information of the fMRI signal, depending on the imaging parameters and settings.
NeuroImage 10/2011; 62(2):1035-9. · 5.89 Impact Factor
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ABSTRACT: Controversial results regarding the detectability of neuronal current magnetic resonance imaging (ncMRI) have been reported in different studies on human subjects. In all the previous studies, the ncMRI signal was detected under a continuous and paradigm task-induced blood oxygen level dependent (BOLD) signal background. The aim of this study is to investigate the possibility of detecting ncMRI signal in human brain in the situation that task-induced BOLD background is absent or minimum. In this study, by adopting an event-related visuomotor paradigm with long interstimulus interval (=20 s), the ncMRI signal was detected when the BOLD signal fully returned to its baseline, and the potential BOLD background contamination was avoided effectively. The results showed that the visuomotor stimulation elicited BOLD activation in visual and motor cortices, but no significant ncMRI signal change (in magnitude) was detected in human brain. These experimental findings are consistent with theoretical predications.
Magnetic Resonance in Medicine 08/2011; 66(2):492-7. · 2.96 Impact Factor
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ABSTRACT: Tissue preparation has recently been utilized for detection of neuronal activation in multiple non-BOLD based functional MRI studies to eliminate vascular contamination. However, undesired signal change could still occur in such systems due to the concentration change of dissolved O(2) upon tissue activation. To estimate the impact of such effects, the O(2) concentration distribution and the consequent susceptibility field in tissue-solution systems were simulated with various tissue geometries and experimental parameters. Our results indicate that substantial signal change between the resting and activated states could potentially be induced by the O(2) effect in highly oxygenated solutions, and thus caution should be taken in interpreting any signal change observed in such experiments.
Magnetic Resonance in Medicine 05/2011; 65(5):1358-64. · 2.96 Impact Factor
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ABSTRACT: How second language (L2) learning is achieved in the human brain remains one of the fundamental questions of neuroscience and linguistics. Previous neuroimaging studies with bilinguals have consistently shown overlapping cortical organization of the native language (L1) and L2, leading to a prediction that a common neurobiological marker may be responsible for the development of the two languages. Here, by using functional MRI, we show that later skills to read in L2 are predicted by the activity level of the fusiform-caudate circuit in the left hemisphere, which nonetheless is not predictive of the ability to read in the native language. We scanned 10-y-old children while they performed a lexical decision task on L2 (and L1) stimuli. The subjects' written language (reading) skills were behaviorally assessed twice, the first time just before we performed the fMRI scan (time 1 reading) and the second time 1 y later (time 2 reading). A whole-brain based analysis revealed that activity levels in left caudate and left fusiform gyrus correlated with L2 literacy skills at time 1. After controlling for the effects of time 1 reading and nonverbal IQ, or the effect of in-scanner lexical performance, the development in L2 literacy skills (time 2 reading) was also predicted by activity in left caudate and fusiform regions that are thought to mediate language control functions and resolve competition arising from L1 during L2 learning. Our findings suggest that the activity level of left caudate and fusiform regions serves as an important neurobiological marker for predicting accomplishment in reading skills in a new language.
Proceedings of the National Academy of Sciences 02/2011; 108(6):2540-4. · 9.68 Impact Factor
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ABSTRACT: Up to date, no consensus has been achieved regarding the possibility of detecting neuronal currents by MRI (ncMRI) in human brain. To evaluate the detectability of ncMRI, an effective way is to simulate ncMRI signal with the realistic neuronal geometry and electrophysiological processes. Unfortunately, previous realistic ncMRI models are based on rat and monkey neurons. The species difference in neuronal morphology and physiology would prevent these models from simulating the ncMRI signal accurately in human subjects. The aim of this study is to bridge this gap by establishing a realistic ncMRI model specifically for human cerebral cortex. In this model, the ncMRI signal was simulated using anatomically reconstructed human pyramidal neurons and their biophysical properties. The modeling results showed that the amplitude of ncMRI signal significantly depends on the density of synchronously firing neurons and imaging conditions such as position of imaging voxel, direction of main magnetic field (B(0) ) relative to the cortical surface and echo time. The results indicated that physiologically-evoked ncMRI signal is too weak to be detected (magnitude/phase change ≤ -1.4 × 10(-6) /0.02°), but the phase signal induced by spontaneous activity may reach a detectable level (up to 0.2°) in favorable conditions.
Magnetic Resonance in Medicine 01/2011; 65(6):1680-9. · 2.96 Impact Factor
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ABSTRACT: To enhance sensitivity in measuring neuronal current MRI (ncMRI) signal using T(2)*-weighted sequences, appropriate selection of echo time (TE) is vital for optimizing data acquisition strategy. The purpose of this study is to establish the contrast-to-noise ratio of neuronal current MRI signal dependence on TE and determine the optimum TE (TE(opt)) in achieving its highest detection power. The TE(opt) in human brain and tissue preparation at 1.5, 3, and 7 T are estimated with different voxel sizes. Our results show that TE(opt) values are different between magnitude and phase images, and TE(opt) is larger in magnitude than phase imaging. This suggests that a dual-echo data acquisition strategy would provide the best efficiency in detecting magnitude and phase neuronal current MRI signals simultaneously. Our results also indicated that the detection sensitivity will be stronger at lower magnetic fields for human brain, whereas the sensitivity will be enhanced/reduced as field strength increases for phase/magnitude imaging on tissue preparation.
Magnetic Resonance in Medicine 12/2010; 64(6):1832-7. · 2.96 Impact Factor
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ABSTRACT: The purpose of this study was to investigate activation-induced hypermetabolism and hyperemia by using a multifrequency (4, 8, and 16 Hz) reversing-checkerboard visual stimulation paradigm. Specifically, we sought to (i) quantify the relative contributions of the oxidative and nonoxidative metabolic pathways in meeting the increased energy demands [i.e., ATP production (J(ATP))] of task-induced neuronal activation and (ii) determine whether task-induced cerebral blood flow (CBF) augmentation was driven by oxidative or nonoxidative metabolic pathways. Focal increases in CBF, cerebral metabolic rate of oxygen (CMRO(2); i.e., index of aerobic metabolism), and lactate production (J(Lac); i.e., index of anaerobic metabolism) were measured by using physiologically quantitative MRI and spectroscopy methods. Task-induced increases in J(ATP) were small (12.2-16.7%) at all stimulation frequencies and were generated by aerobic metabolism (approximately 98%), with %DeltaJ(ATP) being linearly correlated with the percentage change in CMRO(2) (r = 1.00, P < 0.001). In contrast, task-induced increases in CBF were large (51.7-65.1%) and negatively correlated with the percentage change in CMRO(2) (r = -0.64, P = 0.024), but positively correlated with %DeltaJ(Lac) (r = 0.91, P < 0.001). These results indicate that (i) the energy demand of task-induced brain activation is small (approximately 15%) relative to the hyperemic response (approximately 60%), (ii) this energy demand is met through oxidative metabolism, and (iii) the CBF response is mediated by factors other than oxygen demand.
Proceedings of the National Academy of Sciences 05/2010; 107(18):8446-51. · 9.68 Impact Factor
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ABSTRACT: Isolated turtle brain/eye preparation has recently been used as a bloodless animal model for detecting the magnetic resonance imaging (MRI) signal changes produced by visually evoked neuronal currents. The present work aims to determine whether checkerboard-patterned or full field flash (blank) stimulation should be used in order to achieve stronger neuronal responses in turtle brain/eye preparation. The knowledge gained in this study is essential for optimizing the visual stimulation methods in functional neuroimaging studies using turtle brain/eye preparation. In this study, visually evoked local field potentials (LFPs) were measured and compared in turtle visual cortex and optic tectum elicited by checkerboard and full field flash stimuli with three different inter-stimulus intervals (ISIs=5, 10, and 16s). It was found that the behavior of neuronal adaptation in the cortical and tectal LFP signals for checkerboard stimulation was comparable to flash stimulation. In addition, there was no significant difference in the LFP peak amplitudes (ISI=16s) between these two stimuli. These results indicate that the intensity of neuronal responses to checkerboard is comparable to flash stimulation. These two stimulation methods should be equivalent in functional neuroimaging studies using turtle brain/eye preparation.
Journal of neuroscience methods 03/2010; 187(1):26-32. · 2.30 Impact Factor
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ABSTRACT: Metabolic physiology and functional neuroimaging have played important and complementary roles over the past two decades. In particular, investigations of the mechanisms underlying functional neuroimaging signals have produced fundamental new insights into hemodynamic and metabolic regulation. However, controversies were also raised as regards the metabolic pathways (oxidative vs. non-oxidative) for meeting the energy demand and driving the increases in cerebral blood flow (CBF) during brain activation. In a recent study, with the concurrent functional MRI-MRS measurements, we found that task-evoked energy demand was predominately met through oxidative metabolism (approximately 98%), despite a small increase in cerebral metabolic rate of oxygen (12-17%). In addition, the task-induced increases in CBF were most likely mediated by anaerobic glycolysis rather than oxygen demand. These observations and others from functional neuroimaging support the activation-induced neuron-astrocyte interactions portrayed by the astrocyte-neuron lactate shuttle model. The concurrent developments of neuroimaging methods and metabolic physiology will also pave the way for the future investigation of cerebral hemodynamics and metabolism in disease states.
Frontiers in Neuroenergetics 01/2010; 2.
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Marco A M Peluso,
David C Glahn,
Koji Matsuo,
E Serap Monkul,
Pablo Najt,
Frank Zamarripa,
Jinqi Li,
Jack L Lancaster,
Peter T Fox, Jia-Hong Gao,
Jair C Soares
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ABSTRACT: The amygdala participates in the detection and control of affective states, and has been proposed to be a site of dysfunction in affective disorders. To assess amygdala processing in individuals with unipolar depression, we applied a functional MRI (fMRI) paradigm previously shown to be sensitive to amygdala function. Fourteen individuals with untreated DSM-IV major depression and 15 healthy subjects were studied using fMRI with a standardized emotion face recognition task. Voxel-level data sets were subjected to a multiple-regression analysis, and functionally defined regions of interest (ROI), including bilateral amygdala, were analyzed with MANOVA. Pearson correlation coefficients between amygdala activation and HAM-D score also were performed. While both depressed and healthy groups showed increased amygdala activity when viewing emotive faces compared to geometric shapes, patients with unipolar depression showed relatively more activity than healthy subjects, particularly on the left. Positive Pearson correlations between amygdala activation and HAM-D score were found for both left and right ROIs in the patient group. This study provides in vivo imaging evidence to support the hypothesis of abnormal amygdala functioning in depressed individuals.
Psychiatry Research 07/2009; 173(2):158-61. · 2.52 Impact Factor
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ABSTRACT: Contradictory reports regarding the detection of neuronal currents have left the feasibility of neuronal current MRI (ncMRI) an open question. Most previous ncMRI studies in human subjects are suspect due to their inability to separate or eliminate hemodynamic effects. In this study, we used a bloodless turtle brain preparation that eliminates hemodynamic effects, to explore the feasibility of detecting visually-evoked ncMRI signals at 9.4 T. Intact turtle brains, with eyes attached, were dissected from the cranium and placed in artificial cerebral spinal fluid. Light flashes were delivered to the eyes to evoke neuronal activity. Local field potential (LFP) and MRI signals were measured in an interleaved fashion. Robust visually-evoked LFP signals were observed in turtle brains, but no significant signal changes synchronized with neuronal currents were found in the ncMRI images. In this study, detection thresholds of 0.1% and 0.1 degrees were set for MRI magnitude and phase signal changes, respectively. The absence of significant signal changes in the MRI images suggests that visually-evoked ncMRI signals in the turtle brain are below these detectable levels.
NeuroImage 07/2009; 47(4):1268-76. · 5.89 Impact Factor
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ABSTRACT: Forty percent of nondemented octogenarians have Braak stages consistent with insular involvement, and may be at risk for "age-related" autonomic dysfunction. The authors examined the association between insular resting cerebral blood flow (rCBF) and cardiovascular functions in 29 nondemented elderly subjects who were highly screened to exclude comorbid cardiovascular disease. Mean insular rCBF was significantly higher on the right than left. However, 35.4% of participants had left dominant rCBF (a high-risk group). Right insular rCBF was significantly lower in the high-risk group. This subset had significantly increased positional drops in systolic blood pressure. While these data cannot address Alzheimer's disease as the specific cause, this possibility is being investigated in other cohorts.
The Journal of neuropsychiatry and clinical neurosciences 02/2009; 21(2):173-80. · 2.34 Impact Factor
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ABSTRACT: This study explored sex effects on the process of risk-taking. We observed that the female participants (n = 10) showed stronger activation in the right insula and bilateral orbitofrontal cortex (OFC) than did the male participants (n = 12) while they were performing in the Risky-Gains task. The female participants also showed stronger activations in the precentral, postcentral, and paracentral regions after receiving punishment feedback. In addition, the strength of neural activity in the insula correlated with the rate of risky behaviors for the female participants but not for the male participants. Similarly, the percent signal changes in the right OFC correlated negatively with the rate of selecting risky choices for the female group. These findings strongly suggest a sex-related influence modulating brain activity during risk-taking tasks. When taking the same level of risk, relative to men, women tend to engage in more neural processing involving the insula and the OFC to update and valuate possible uncertainty associated with risk-taking decision making. These results are consistent with the value-based decision-making model and offer insights into the possible neural mechanisms underlying the different risk-taking attitudes of men and women.
Cerebral Cortex 11/2008; 19(6):1303-12. · 6.54 Impact Factor
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ABSTRACT: The purpose of this study is to determine whether blood inflow impacts the temporal behavior of BOLD-contrast fMRI signal changes in a typical event-related paradigm. The inflow contributions in the hemodynamic response to repeated single trials of short visual stimulation were assessed with a gradient-echo EPI sequence by altering the flip angle (FA) from 30 degrees to 90 degrees at a repetition time of 1 s. For each FA condition (30 degrees, 60 degrees, and 90 degrees), 30 trials were performed on 15 healthy volunteers on a 3T MRI scanner. Comparing the percent BOLD contrast, prominent inflow effects were found with statistical significance between the 90 degrees- and 30 degrees-FA conditions (0.73 +/- 0.15 versus 0.67 +/- 0.12%, p=0.028). BOLD responses with FA=30 degrees exhibited latencies significantly slower than those with FA=90 degrees (3.69 +/- 0.39 s versus 3.37 +/- 0.28 s, p=0.001). The falling time of the 30 degrees-FA responses was earlier but not statistically different from that of the 90 degrees-FA (8.17 +/- 1.04 s versus 8.03 +/- 1.15 s, p=0.3). Using a voxelwise analysis, the latency variations of the activated visual areas were determined at several contrast-to-noise ratio (CNR) levels (controlled by averaging different numbers of randomly selected trials). The latency variations from the 90 degrees-FA responses were greater at lower CNR but similar at higher CNR levels when comparing to the 30 degrees-FA ones. This study suggests that inflow effects contribute to the BOLD signal, resulting in hemodynamic response with shorter latency.
Medical Physics 11/2008; 35(10):4300-7. · 2.83 Impact Factor
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ABSTRACT: The aim of this study was to investigate the relationship between relative cerebral blood flow (delta CBF) and relative cerebral metabolic rate of oxygen (delta CMRO(2)) during continuous visual stimulation (21 min at 8 Hz) with fMRI biophysical models by simultaneously measuring of BOLD, CBF and CBV fMRI signals. The delta CMRO(2) was determined by both a newly calibrated single-compartment model (SCM) and a multi-compartment model (MCM) and was in agreement between these two models (P>0.5). The duration-varying delta CBF and delta CMRO(2) showed a negative correlation with time (r=-0.97, P<0.001); i.e., delta CBF declines while delta CMRO(2) increases during continuous stimulation. This study also illustrated that without properly calibrating the critical parameters employed in the SCM, an incorrect and even an opposite appearance of the flow-metabolism relationship during prolonged visual stimulation (positively linear coupling) can result. The time-dependent negative correlation between flow and metabolism demonstrated in this fMRI study is consistent with a previous PET observation and further supports the view that the increase in CBF is driven by factors other than oxygen demand and the energy demands will eventually require increased aerobic metabolism as stimulation continues.
NeuroImage 10/2008; 44(1):16-22. · 5.89 Impact Factor
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ABSTRACT: The aim of this study was to investigate the various MRI biophysical models in the measurements of local cerebral metabolic rate of oxygen (CMRO(2)) and the corresponding relationship with cerebral blood flow (CBF) during brain activation. This aim was addressed by simultaneously measuring the relative changes in CBF, cerebral blood volume (CBV), and blood oxygen level dependent (BOLD) MRI signals in the human visual cortex during visual stimulation. A radial checkerboard delivered flash stimulation at five different frequencies. Two MRI models, the single-compartment model (SCM) and the multicompartment model (MCM), were used to determine the relative changes in CMRO(2) using three methods: [1] SCM with parameters identical to those used in a prior MRI study (M = 0.22; alpha = 0.38); [2] SCM with directly measured parameters (M from hypercapnia and alpha from measured deltaCBV and deltaCBF); and [3] MCM. The magnitude of relative changes in CMRO(2) and the nonlinear relationship between CBF and CMRO(2) obtained with Methods [2] and [3] were not in agreement with those obtained using Method [1]. However, the results of Methods [2] and [3] were aligned with positron emission tomography findings from the literature. Our results indicate that if appropriate parameters are used, the SCM and MCM models are equivalent for quantifying the values of CMRO(2) and determining the flow-metabolism relationship.
Magnetic Resonance in Medicine 09/2008; 60(2):380-9. · 2.96 Impact Factor
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ABSTRACT: This event-related functional Magnetic Resonance Imaging study examined the differential neural activities associated with a Risky-Gains task in 18 healthy individuals of high (n=9) or low (n=9) impulsiveness, according to their scores on the Barratt Impulsiveness Scale (BIS). The neural activities of people belonging to the high and low impulsiveness groups were monitored by a 3T MRI scanner while they were performing the Risky-Gains task. We demonstrated that a stronger activation in the insula-orbitofrontal-parietal regions was found in the high impulsiveness group compared to the low impulsiveness group. However, the levels of activation in the lateral prefrontal and anterior cingulate regions did not differ between the two groups. The findings suggest that the neural substrates of comprehension of cognitive and affective information associated with risk-taking decision making may vary according to the impulsiveness among healthy individuals.
Neuroscience Letters 07/2008; 438(2):138-41. · 2.11 Impact Factor
