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James J Pekar

Publications and source records attributed to James J Pekar.

13 recordsLinked to original sources

A method for multitask fMRI data fusion applied to schizophrenia.

It is becoming common to collect data from multiple functional magnetic resonance imaging (fMRI) paradigms on a single individual. The data from these experiments are typically analyzed separately and sometimes directly subtracted from one another on a voxel-by-voxel basis. These comparative approaches, although useful, do not directly attempt to examine potential commonalities between tasks and between voxels. To remedy this we propose a method to extract maximally spatially independent maps for each task that are "coupled" together by a shared loading parameter. We first compute an activation map for each task and each individual as "features," which are then used to perform joint independent component analysis (jICA) on the group data. We demonstrate our approach on a data set derived from healthy controls and schizophrenia patients, each of which carried out an auditory oddball task and a Sternberg working memory task. Our analysis approach revealed two interesting findings in the data that were missed with traditional analyses. First, consistent with our hypotheses, schizophrenia patients demonstrate "decreased" connectivity in a joint network including portions of regions implicated in two prevalent models of schizophrenia. A second finding is that for the voxels identified by the jICA analysis, the correlation between the two tasks was significantly higher in patients than in controls. This finding suggests that schizophrenia patients activate "more similarly" for both tasks than do controls. A possible synthesis of both findings is that patients are activating less, but also activating with a less-unique set of regions for these very different tasks. Both of the findings described support the claim that examination of joint activation across multiple tasks can enable new questions to be posed about fMRI data. Our approach can also be applied to data using more than two tasks. It thus provides a way to integrate and probe brain networks using a variety of tasks and may increase our understanding of coordinated brain networks and the impact of pathology upon them.

Adult↗

Theoretical and experimental investigation of the VASO contrast mechanism.

Vascular space occupancy (VASO)-dependent functional MRI (fMRI) is a blood-nulling technique capable of generating microvascular cerebral blood volume (CBV)-weighted images. It is shown that at high magnetic field (3.0T) and high spatial resolution (1.89 x 1.89 x 3 mm(3)), the VASO signal changes are too large (6-7%) to originate from CBV effects alone. Additional contributions are investigated theoretically and experimentally as a function of MRI parameters (TR and TE), as well as the signal-to-noise ratio, (SNR) and spatial resolution. First, it is found that an arterial spin labeling (ASL) contribution causes large negative VASO signal changes at short TR. Second, even at high fMRI spatial resolution, CSF volume contributions (7-13%) cause VASO signal changes to become more negative, most noticeably at long TR and TE. Third, white matter (WM) effects reduce signal changes at lower spatial resolution. The VASO technique has been tested using different stimulus paradigms and field strengths (1-3), giving results consistent with comparable tasks investigated using BOLD and cerebral blood flow (CBF)-based techniques. Finally, simulations show that a mixture of fresh and steady-state blood may significantly alter signal changes at short TR (< or =3 s), permitting larger VASO signal changes than expected under pure steady-state conditions. Thus, many competing effects contribute to VASO contrast and care should be taken during interpretation.

Adult↗

An account of the discrepancy between MRI and PET cerebral blood flow measures. A high-field MRI investigation.

There is controversy concerning the discrepancy between absolute cerebral blood flow (CBF) values measured using positron emission tomography (PET) and magnetic resonance imaging (MRI). To gain insight into this problem, the increased signal-to-noise ratio (SNR) and extended T(1) relaxation times of blood and tissue at 3.0 T were exploited to perform pulsed arterial spin labeling (PASL) MRI measurements as a function of spatial resolution and post-labeling delay. The results indicate that, when using post-labeling delays shorter than 1500 ms, MRI gray matter flow values may become as high as several times the correct CBF values owing to tissue signal contamination by remaining arterial blood water label. For delays above 1500 ms, regional PASL-based CBF values (n = 5; frontal gray matter: 48.8 +/- 3.3(SD) ml/100 g/min; occipital gray matter: 49.3 +/- 4.5 ml/100 g/min) comparable with PET-based measurements can be obtained by using spatial resolutions comparable with PET (5-7.5 mm in-plane). At very high resolution (2.5 x 2.5 x 3 mm(3)), gray matter CBF values were found to increase by 10-20%, a consequence attributed to reduction in partial volume effects with cerebrospinal fluid and white matter. The recent availability of MRI field strengths of 3.0 T and higher will facilitate the use of MRI-based CBF measurements in the clinic.

Blood Flow Velocity↗

Atypical motor and sensory cortex activation in attention-deficit/hyperactivity disorder: a functional magnetic resonance imaging study of simple sequential finger tapping.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) has been shown to be associated with anomalous motor development, including excessive overflow movements. The neurological basis of these deficits has not been established. Functional magnetic resonance imaging (fMRI) was used to determine whether differences in brain activation during sequential finger tapping are present in children with ADHD compared with typically developing control subjects. METHODS: Twenty-two right-handed children between 8 and 12 years old, 11 with ADHD and 11 typically developing control subjects closely matched for age and gender, performed self-paced sequential finger tapping during fMRI acquisition. RESULTS: There were no significant between-group differences in speed of sequential finger tapping. The between-group whole-brain comparison showed greater magnitude of activation for control subjects than children with ADHD in the right superior parietal lobe during both right-handed and left-handed finger tapping. The region-of-interest analysis within Brodmann Area 4 revealed that children with ADHD showed a significantly smaller extent of fMRI activation in the primary motor cortex contralateral to the finger-sequencing hand. CONCLUSIONS: Despite similar speed of sequential finger tapping, children with ADHD showed decreased contralateral motor cortex and right parietal cortex activation during both right-handed finger sequencing (RHFS) and left-handed finger sequencing (LHFS). The fMRI findings suggest that children with ADHD have anomalous development of cortical systems necessary for execution of patterned movements.

Analysis of Variance↗

Functional brain changes in presymptomatic Huntington's disease.

Evidence suggests early structural brain changes in individuals with the Huntington's disease (HD) genetic mutation who are presymptomatic for the movement symptoms of the illness. The aim of this study was to investigate the presence of functional brain changes in this same population using functional magnetic resonance imaging. Subjects and matched controls underwent an functional magnetic resonance imaging "interference" protocol, a task known to be mediated in part by corticostriatal circuitry. In the setting of normal cognitive performance, presymptomatic HD subjects had significantly and specifically less activation in the left anterior cingulate cortex (BA 24, 32) compared with matched controls.

Adult↗

A method for comparing group fMRI data using independent component analysis: application to visual, motor and visuomotor tasks.

Independent component analysis (ICA) is an approach for decomposing fMRI data into spatially independent maps and time courses. We have recently proposed a method for ICA of multisubject data; in the current paper, an extension is proposed for allowing ICA group comparisons. This method is applied to data from experiments designed to stimulate visual cortex, motor cortex or both visual and motor cortices. Several intergroup and intragroup metrics are proposed for assessing the utility of the components for comparisons of group ICA data. The proposed method may prove to be useful in answering questions requiring multigroup comparisons when a flexible modeling approach is desired.

Adult↗

Alcohol intoxication effects on simulated driving: exploring alcohol-dose effects on brain activation using functional MRI.

Driving while intoxicated is a major public health problem. We investigated impaired driving using a simulated driving skill game that presents an 'in-car' view of a road and a readout of speed. We explored brain activation and behavioral alterations from baseline at two blood alcohol concentrations (BACs). Participants received single-blind individualized doses of beverage alcohol designed to produce blood alcohol content (BAC) of 0.04 and 0.08 or placebo. Scanning occurred on a 1.5 Tesla Philips MRI scanner after training to asymptote performance. Analysis was performed using independent component analysis (ICA) to isolate systematically nonoverlapping 'networks' and their time courses. Imaging results revealed seven separate driving-related brain networks with different time courses. Several significant findings were observed for the imaging data. First, dose-dependent functional magnetic resonance imaging (fMRI) changes were revealed in orbitofrontal (OF) and motor (but not cerebellar) regions; visual and medial frontal regions were unaffected. Second, cerebellar regions were significantly associated with driving behavior in a dose-dependent manner. Finally, a global disruptive effect of alcohol on the ICA time courses was observed with highly significant differences in OF and motor regions. Alcohol thus demonstrated some behavioral effects and unique, disruptive, dose-dependent effects on fMRI signal within several brain circuits. The fMRI data also suggest that the deficits observed in alcohol intoxication may be modulated primarily through OF/anterior cingulate, motor and cerebellar regions as opposed to attentional areas in frontoparietal cortex.

Adult↗

Sustained poststimulus elevation in cerebral oxygen utilization after vascular recovery.

The brain's response to functional activation is characterized by focal increases in cerebral blood flow. It is generally assumed that this hyperemia is a direct response to the energy demands of activation, the so-called flow-metabolism coupling. Here we report experimental evidence that increases in oxygen metabolism can occur after activation without increases in flow. When using multimodality functional MRI (fMRI) to study visual activation in human brain, we observed a postactivation period of about 30 seconds during which oxygen consumption remained elevated, while blood flow and volume had already returned to baseline levels. The finding of such a prolonged and complete dissociation of vascular response and energy metabolism during the poststimulus period indicates that increased metabolic demand needs not per se cause a concomitant increase in blood flow. The results also show that the postactivation undershoot after the positive blood-oxygen-level-dependent hemodynamic response in fMRI should be reinterpreted as a continued elevation of oxygen metabolism, rather than a delayed blood volume compliance.

Adult↗

Functional magnetic resonance imaging based on changes in vascular space occupancy.

During brain activation, local control of oxygen delivery is facilitated through microvascular dilatation and constriction. A new functional MRI (fMRI) methodology is reported that is sensitive to these microvascular adjustments. This contrast is accomplished by eliminating the blood signal in a manner that is independent of blood oxygenation and flow. As a consequence, changes in cerebral blood volume (CBV) can be assessed through changes in the remaining extravascular water signal (i.e., that of parenchymal tissue) without need for exogenous contrast agents or any other invasive procedures. The feasibility of this vascular space occupancy (VASO)-dependent functional MRI (fMRI) approach is demonstrated for visual stimulation, breath-hold (hypercapnia), and hyperventilation (hypocapnia). During visual stimulation and breath-hold, the VASO signal shows an inverse correlation with the stimulus paradigm, consistent with local vasodilatation. This effect is reversed during hyperventilation. Comparison of the hemodynamic responses of VASO-fMRI, cerebral blood flow (CBF)-based fMRI, and blood oxygenation level-dependent (BOLD) fMRI indicates both arteriolar and venular temporal characteristics in VASO. The effect of changes in water exchange rate and partial volume contamination with CSF were calculated to be negligible. At the commonly-used fMRI resolution of 3.75 x 3.75 x 5 mm(3), the contrast-to-noise-ratio (CNR) of VASO-fMRI was comparable to that of CBF-based fMRI, but a factor of 3 lower than for BOLD-fMRI. Arguments supporting a better gray matter localization for the VASO-fMRI approach compared to BOLD are provided.

Adult↗

fMRI evidence that the neural basis of response inhibition is task-dependent.

Event-related fMRI was used to investigate the hypothesis that neural activity involved in response inhibition depends upon the nature of the response being inhibited. Two different Go/No-go tasks were compared-one with a high working memory load and one with low. The 'simple' Go/No-go task with low working memory load required subjects to push a button in response to green spaceships but not red spaceships. A 'counting' Go/No-go task (high working memory load) required subjects to respond to green spaceships as well as to those red spaceships preceded by an even number of green spaceships. In both tasks, stimuli were presented every 1.5 s with a 5:1 ratio of green-to-red spaceships. fMRI group data for each task were analyzed using random effects models to determine signal change patterns associated with Go events and No-go events (corrected P< or =0.05). For both tasks, Go responses were associated with signal change in the left primary sensorimotor cortex, supplementary motor area (SMA) proper, and anterior cerebellum (right>left). For the simple task, No-go events were associated with activation in the pre-SMA; the working memory-loaded 'counting' task elicited additional No-go activation in the right dorsolateral prefrontal cortex. The findings suggest that neural contributions to response inhibition may be task dependent; the pre-SMA appears necessary for inhibition of unwanted movements, while the dorsolateral prefrontal cortex is recruited for tasks involving increased working memory load.

Adult↗

Different activation dynamics in multiple neural systems during simulated driving.

Driving is a complex behavior that recruits multiple cognitive elements. We report on an imaging study of simulated driving that reveals multiple neural systems, each of which have different activation dynamics. The neural correlates of driving behavior are identified with fMRI and their modulation with speed is investigated. We decompose the activation into interpretable pieces using a novel, generally applicable approach, based upon independent component analysis. Some regions turn on or off, others exhibit a gradual decay, and yet others turn on transiently when starting or stopping driving. Signal in the anterior cingulate cortex, an area often associated with error monitoring and inhibition, decreases exponentially with a rate proportional to driving speed, whereas decreases in frontoparietal regions, implicated in vigilance, correlate with speed. Increases in cerebellar and occipital areas, presumably related to complex visuomotor integration, are activated during driving but not associated with driving speed.

Adult↗

Transient neural activity in human parietal cortex during spatial attention shifts.

Observers viewing a complex visual scene selectively attend to relevant locations or objects and ignore irrelevant ones. Selective attention to an object enhances its neural representation in extrastriate cortex, compared with those of unattended objects, via top-down attentional control signals. The posterior parietal cortex is centrally involved in this control of spatial attention. We examined brain activity during attention shifts using rapid, event-related fMRI of human observers as they covertly shifted attention between two peripheral spatial locations. Activation in extrastriate cortex increased after a shift of attention to the contralateral visual field and remained high during sustained contralateral attention. The time course of activity was substantially different in posterior parietal cortex, where transient increases in activation accompanied shifts of attention in either direction. This result suggests that activation of the parietal cortex is associated with a discrete signal to shift spatial attention, and is not the source of a signal to continuously maintain the current attentive state.

Adult↗