2006 — 2007 |
Buracas, Giedrius T |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Neuromodulation of Bold Fmri Signal During Cognitive Tasks @ University of California San Diego
[unreadable] DESCRIPTION (provided by applicant): Blood oxygenation level dependent (BOLD) functional MRI (fMRI) has become a workhorse method for noninvasively measuring brain activity during sensorimotor and cognitive tasks and an indispensable diagnostic tool for neurological disorders. BOLD signal is a function of regional cerebral blood flow (rCBF), blood volume (rCBV), and the regional cerebral metabolic rate of oxygen (rCMRO2), and the understanding of the coupling of these factors to the neuronal activity is far from complete. Among those three factors contributing to BOLD, rCBF is probably most susceptible to nonlocal factors, such vasoactive metabolites (such as CO2), hormones, and non-localy released neuromodulators that control brain states such as vigilance, alertness, attention, etc. Indeed, neuromodulators controlling brain states (e.g. acetylcholine, norepinephrine, serotonin, dopamine, etc) exhibit vasoactive properties and cerebral vasculature is known to be innervated by neuronal terminals expressing these neuromodulators. Among these, cholinergic neuromodulatory system is of special interest, since it plays essential role during cognitive tasks engaging selective attention, working memory and learning mechanisms. Imaging of brain activation during tasks engaging this neuromodulatory system is problematic, since cholinergic neuromodulatory system is also involved in global control of cerebral perfusion. We propose to address the role of acetylcholine (Ach), in shaping the relationship between local neuronal activation and BOLD responses during cognitive tasks by testing the following working hypothesis: Regional CBF is regulated not only by local neuronal activity but also by factors controlling allocation of attention and working memory resources, mediated by cholinergic systems. This systemic regulation of rCBF may change the relationship between neuronal activity (as indexed by rCMRO2) and rCBF. We hypothesize that acetylcholine release is essential for mediation of coupling between neuronal responses and CBF during attention and working memory tasks (probably via activation of basal forebrain). We propose to test these hypotheses by measuring CBF and BOLD responses using arterial spin labeling (ASL) method. We will test whether allocation of attentional resources affects BOLD and CBF signal in the same manner as stimulation by visual stumuli alone. In order to investigate the role of cholinergic mechanisms in coupling between CBF and BOLD during cognitive tasks, we will use pharmacological manipulations to affect efficacy of cholinergic modulation. We expect that pharmacological manipulations of the cholinergic modulation will affect CBF/BOLD relationship in the same direction as allocation of attention resources. Proposed experiments will set the ground for systematic inquiry into effects of neuromodulators on coupling between BOLD signal and underlying local neuronal activity, and will develop tools for addressing neuromodulatory mechanisms of cognitive processes by means of fMRI. [unreadable] [unreadable]
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2008 — 2009 |
Buracas, Giedrius T |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Mri of Weak Periodic Currents Using Balanced Steady State Free Precession @ University of California San Diego
[unreadable] DESCRIPTION (provided by applicant): Existing functional brain MR imaging methods such as blood oxygenation level dependent (BOLD) imaging are based on vascular and metabolic responses to variations in underlying neuronal activity and thus reflect the latter only indirectly. It has been proposed (e.g. Bodurka & Bandettini, 2002) that magnetic field perturbations caused by neuronal currents in the brain in principle ought to be detectable by means of MRI. Several research groups have demonstrated the feasibility of this idea in theory, electric current phantoms and in vivo. However, relatively low signal-to-noise ratio achieved to date renders existing methods impractical. Balanced Steady State Free Precession (bSSFP, also known as TrueFISP, FIESTA) pulse sequence is unique in that it can afford the highest known SNR per unit time and thus application of bSSFP for functional neural current imaging can potentially solve the problem of low SNR. Recent studies suggest that certain SSFP sequences might be exquisitely sensitive to minute periodic perturbations of the spin phase. Thus, periodic currents locked to RF excitation pulse result in an alternating balanced steady state (ABSS) that can effectively amplify the phase offset induced by currents. Our theoretical calculations and the data acquired with bSSFP at 3T using a current phantom indicates SNR of the signal induced by periodic currents that is substantially superior to that achieved previously using standard gradient and spin echo imaging (Buracas et al., 2007). We propose to develop optimized alternating steady-state imaging protocols for imaging of periodic electric currents. First, we will optimize, analytically, in computer simulations, and current phantom experiments the sensitivity of the ABSS method to weak periodic currents and address the impact of various sources of noise on the ABSS signal. Next, we will apply this method to imaging neuronal currents in vivo (using rat whisker stimulation and human audiovisual stimulation paradigms). We will implement noise compensation for magnetic field fluctuation due to respiration and scanner drift and motion compensation. In conclusion, the current proposal will address the possibility to measure electromagnetic correlates of cerebral neuronal activity by means of ABSS and will address critical sources of noise. Accomplishment of the proposed aims has a potential of introducing a new imaging modality for functional brain imaging - high resolution MRI-based magnetoencephalography. PUBLIC HEALTH RELEVANCE: Established functional brain MR imaging methods are susceptible to factors influencing neurovascular coupling. It has been recently proposed and demonstrated that MRI can be used for imaging neuronal currents directly, but existing methods are impractical due to their low SNR. The proposed research will develop ultra- sensitive MRI methods for imaging neuronal currents using balanced Steady State Free Precession pulse sequences that possess best known SNR efficiency. [unreadable] [unreadable] [unreadable]
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