Biomedical subjects

B Douglas Ward

Publications and source records attributed to B Douglas Ward.

10 recordsLinked to original sources

PubMed2006

State-space estimation of the input stimulus function using the Kalman filter: a communication system model for fMRI experiments.

The blood oxygenation level-dependent (BOLD) signal measured in functional magnetic resonance imaging (fMRI) experiments in response to input stimuli is temporally delayed and distorted due to the blurring effect of the voxel hemodynamic impulse response function (IRF). Knowledge of the IRF, obtained during the same experiment, or as the result of a separate experiment, can be used to dynamically obtain an estimate of the input stimulus function. Reconstruction of the input stimulus function allows the fMRI experiment to be evaluated as a communication system. The input stimulus function may be considered as a "message" which is being transmitted over a noisy "channel", where the "channel" is characterized by the voxel IRF. Following reconstruction of the input stimulus function, the received message is compared with the transmitted message on a voxel-by-voxel basis to determine the transmission error rate. Reconstruction of the input stimulus function provides insight into actual brain activity during task activation with less temporal blurring, and may be considered as a first step toward estimation of the true neuronal input function.

Adult↗

PubMed2006

Measurements of tissue T1 spin-lattice relaxation time and discrimination of large draining veins using transient EPI data sets in BOLD-weighted fMRI acquisitions.

The signal intensity during the dynamic approach to the equilibrium state of longitudinal magnetization is a function of sequence parameters, such as repetition time and flip angle, and depends on tissue characteristics, including longitudinal relaxation time of stationary tissue and the rate of blood inflow. A method is presented to extract information from data acquired during the transient state prior to T1 equilibrium using echo-planar acquisitions in T2*-weighted functional magnetic resonance imaging (fMRI) experiments. A voxel in a single slice acquisition is assumed to contain either stationary tissue or large vessels with flowing blood. Models are presented to characterize longitudinal magnetization relaxation of heterogeneous stationary tissue and blood inflow. The data were fitted to theoretical models for longitudinal relaxation of stationary tissue and inflowing blood assuming no residual signal prior to each RF excitation. Parameters were estimated at 3 T for each model using least squares estimation. A goodness-of-fit criterion was applied to exclude voxels that have transient data that does not fit the selected (best fit) model. Voxels that best fit the inflow model, measured at various TR and flip angles, were assumed to contain large draining veins and were excluded from functional maps. Histogram analysis of T1 distributions for activated voxels in a visual paradigm demonstrated the distributions are centered at T1 values of gray matter with tails at both sides of the center due to partial voluming of gray matter with white matter and CSF respectively. The mean gray matter volume fraction in activated voxels was about 0.9. The results indicate that transient data sets can provide additional information that is useful for both localization and characterization of the functionally relevant BOLD response.

Adult↗

PubMed2006

Peripheral blood pressure changes induced by dobutamine do not alter BOLD signals in the human brain.

In extending the use of functional MRI to neuropharmacology, a primary area of concern is that peripheral blood pressure changes induced by pharmacological agents could independently produce a change in the blood oxygenation level-dependent (BOLD) signal, resulting in difficulties distinguishing or interpreting drug-induced neural activations. In the present study, we utilized intravenous dobutamine, a beta-adrenergic receptor agonist, to increase the mean arterial blood pressure (MABP), while examining the effects of MABP changes on the BOLD signal in cocaine-dependent participants. Dobutamine infusion significantly increased the MABP from 93 +/- 8 mm Hg to 106 +/- 12 mm Hg (P < 0.0005), but did not produce a significant global BOLD signal. Yet, a few voxels in the anterior cingulate showed BOLD signal changes that paralleled the changes in blood pressure (BP). Our observations support the conclusion that following the infusion of psychoactive agents, brain BOLD signals accurately reflect neuronal activity, even in the face of relatively large peripheral cardiovascular effects that transiently increase systemic BP.

Adrenergic beta-Agonists↗

PubMed2005

Volatile anesthetics disrupt frontal-posterior recurrent information transfer at gamma frequencies in rat.

We seek to understand neural correlates of anesthetic-induced unconsciousness. We hypothesize that cortical integration of sensory information may underlie conscious perception and may be disrupted by anesthetics. A critical role in frontal-posterior interactions has been proposed, and gamma (20-60 Hz) oscillations have also been assigned an essential role in consciousness. Here we investigated whether general anesthetics may interfere with the exchange of information encoded in gamma oscillations between frontal and posterior cortices. Bipolar electrodes for recording of event-related potentials (ERP) were chronically implanted in the primary visual cortex, parietal association and frontal association cortices of six rats. Sixty light flashes were presented every 5s, and ERPs were recorded at increasing concentrations of halothane or isoflurane (0-2%). Information exchange was estimated by transfer entropy, a novel measure of directional information transfer. Transfer entropy was calculated from 1-s wavelet-transformed ERPs. We found that (1) feedforward transfer entropy (FF-TE) and feedback transfer entropy (FB-TE) were balanced in conscious-sedated state; (2) anesthetics at concentrations producing unconsciousness augmented both FF-TE and FB-TE at 30 Hz but reduced them at 50 Hz; (3) reduction at 50 Hz was more pronounced for FB-TE, especially between frontal and posterior regions; (4) at high concentrations, both FF-TE and FB-TE at all frequencies were at or below conscious-sedated baseline. Our findings suggest that inhalational anesthetics preferentially impair frontal-posterior FB information transfer at high gamma frequencies consistent with the postulated role of frontal-posterior interactions in consciousness.

Anesthetics, Inhalation↗

PubMed2005

Temporal evolution of the CBV-fMRI signal to rat whisker stimulation of variable duration and intensity: a linearity analysis.

Cerebral blood volume functional magnetic resonance imaging (CBV-fMRI) experiments employing iron oxide contrast agent were conducted in rat whisker barrel cortex at 3 Tesla. Stimuli of constant frequency (12 Hz) but variable duration and intensity were delivered separately using a homemade whisker stimulator. The temporal behavior of CBV-fMRI signals was investigated using a linearity analysis method. Both superposition and scaling tests show that CBV-fMRI responses are generally consistent with a linear time-invariant (LTI) model. In particular, the response to a stimulus of higher intensity can be linearly scaled from that of lower intensity. However, significant deviations exist when the stimulus duration is manipulated, particularly in the trailing edge of the CBV-fMRI response curves.

Animals↗

PubMed2005

Characterizing extravascular fluid transport of macromolecules in the tumor interstitium by magnetic resonance imaging.

Noninvasive imaging techniques to image and characterize delivery and transport of macromolecules through the extracellular matrix (ECM) and supporting stroma of a tumor are necessary to develop treatments that alter the porosity and integrity of the ECM for improved delivery of therapeutic agents and to understand factors which influence and control delivery, movement, and clearance of macromolecules. In this study, a noninvasive imaging technique was developed to characterize the delivery as well as interstitial transport of a macromolecular agent, albumin-GdDTPA, in the MCF-7 human breast cancer model in vivo, using magnetic resonance imaging. The transport parameters derived included vascular volume, permeability surface area product, macromolecular fluid exudate volume, and drainage and pooling rates. Immunohistochemical staining for the lymphatic endothelial marker LYVE-1 was done to determine the contribution of lymphatics to the macromolecular drainage. Distinct pooling and draining regions were detected in the tumors using magnetic resonance imaging. A few lymphatic vessels positively stained for LYVE-1 were also detected although these were primarily collapsed and tenuous suggesting that lymphatic drainage played a minimal role, and that the bulk of drainage was due to convective transport through the ECM in this tumor model.

Albumins↗

PubMed2005

Volatile anesthetics enhance flash-induced gamma oscillations in rat visual cortex.

BACKGROUND: The authors sought to understand neural correlates of anesthetic-induced unconsciousness. Cortical gamma oscillations have been associated with neural processes supporting conscious perception, but the effect of general anesthesia on these oscillations is controversial. In this study, the authors examined three volatile anesthetics, halothane, isoflurane, and desflurane, and compared their effects on flash-induced gamma oscillations in terms of equivalent concentrations producing the loss of righting reflex (1 minimum alveolar concentration for the loss of righting [MAC(LR)]). METHODS: Light flashes were presented every 5 s for 5 min, and event-related potentials were recorded from primary visual cortex of 15 rats with a chronically implanted bipolar electrode at increasing anesthetic concentrations (0-2.4 MAC(LR)). Early cortical response was obtained by averaging poststimulus (0-100 ms) potentials filtered at 20-60 Hz across 60 trials. Late (100-1,000 ms) gamma power was calculated using multitaper power spectral technique. Wavelet decomposition was used to determine spectral and temporal distributions of gamma power. RESULTS: The authors found that (1) halothane, isoflurane, and desflurane enhanced the flash-evoked early cortical response in a concentration-dependent manner; (2) the effective concentration for this enhancement was the lowest for isoflurane, intermediate for halothane, and the highest for desflurane when compared at equal fractions of the concentration that led to a loss of righting; (3) the power of flash-induced late (> 100 ms) gamma oscillations was augmented at intermediate concentrations of all three anesthetic agents; and (4) flash-induced gamma power was not reduced below waking baseline even in deep anesthesia. CONCLUSIONS: These findings suggest that a reduction in flash-induced gamma oscillations in rat visual cortex is not a unitary correlate of anesthetic-induced unconsciousness.

Anesthetics, Inhalation↗

PubMed2004

Neural correlates of sensory and decision processes in auditory object identification.

Physiological studies of auditory perception have not yet clearly distinguished sensory from decision processes. In this experiment, human participants identified speech sounds masked by varying levels of noise while blood oxygenation signals in the brain were recorded with functional magnetic resonance imaging (fMRI). Accuracy and response time were used to characterize the behavior of sensory and decision components of this perceptual system. Oxygenation signals in a cortical subregion just anterior and lateral to primary auditory cortex predicted accuracy of sound identification, whereas signals in an inferior frontal region predicted response time. Our findings provide neurophysiological evidence for a functional distinction between sensory and decision mechanisms underlying auditory object identification. The present results also indicate a link between inferior frontal lobe activation and response-selection processes during auditory perception tasks.

Acoustic Stimulation↗

PubMed2004

Spatial correlations of laminar BOLD and CBV responses to rat whisker stimulation with neuronal activity localized by Fos expression.

The spatial relationship between a measured fMRI signal and its underlying neuronal activity remains unclear. One obstacle is the localization of neuronal activity; another is the spatial resolution of fMRI. In the present study, high-resolution BOLD and CBV fMRI experiments (voxel size: 156 x 156 x 2000 microm3) were conducted in the rat whisker barrel cortex at 3 T; neuronal activity across cortical layers was mapped using the Fos expression technique. Results show that BOLD response is weighted by blood volume and that pixels with high BOLD response can be located at the cortical surface or in deep layers, depending on local vasculature. In contrast to BOLD response, the pixels with high CBV response were consistently clustered in the deep cortical layers. Percentage-CBV change in cortical layers IV-V was 7.3 +/- 1.5%, which was significantly higher than in layers I-III (4.1 +/- 0.9%) and VI (4.3 +/- 0.7%) (mean +/- SEM). The laminar distribution of CBV response correlates well with neuronal activity localized by Fos expression. We conclude that neuronal activity can be inferred from CBV fMRI data with high spatial accuracy. The data indicate that both intracolumn functional connectivity and neurovascular coupling can be studied using CBV fMRI.

Animals↗

PubMed2003

Single-shot magnetic field mapping embedded in echo-planar time-course imaging.

A technique for acquiring magnetic field maps simultaneously with gradient-recalled echo-planar time-course data is described. This technique uses a trajectory in which the central part of k-space is collected twice. For a 64 x 64 image acquired with a 125-kHz bandwidth, a field map suitable for geometric correction can be collected simultaneously with the echo-planar time-course data in <70 ms. The field maps generated by this technique are registered with the magnitude images because they are calculated using the same data. They do not suffer from errors due to subject motion, or from different geometric distortions that can result from using different pulse sequences. In addition to correcting geometric distortions that resulted from dynamic magnetic field perturbations, this method was used to measure field shifts arising from respiration and jaw motion across five subjects. Values ranged from 0.035 to 0.165 parts per million (ppm).

Brain↗