Faculty Bibliography

The proportionality of blood oxygen level-dependent (BOLD) response during a cognitive task and that from a hypercapnic challenge was investigated in cortical structures involved in working memory (WM). Breath holding (BH) following inspiration was used to induce a BOLD response characteristic of regional vasomotor reactivity but devoid of metabolic changes. BOLD effects measured during BH were used to normalize individual subject activations during WM, which effectively reduced the confounding influence of individual- and region-specific differences in hemodynamic responsivity common to both tasks. In a study of seven subjects, the BH calibration reduced intersubject variability in WM effect amplitude by 24.8% (P < 0.03). Reduced intersubject variability resulted in a 23.7% increase in group WM activation voxel extent significant at P < 0.001, with further increases at more stringent thresholds. Because the BH task does not require CO(2) inhalation or other invasive manipulations and is broadly applicable across cortical regions, the proposed approach is simple to implement and may be beneficial for use not only in quantitative group fMRI analyses, but also for multicenter and longitudinal studies.

Behavioral studies suggest that emotional reactivity in depressed persons predicts subsequent symptom reduction. Using functional magnetic resonance imaging in a prospective study, we show that greater amygdala activation to emotional facial expressions among depressed patients predicts symptom reduction 8 months later, controlling for initial depression severity and medication status. Functional magnetic resonance imaging may thus be used as a method to identify neural markers in depressed patients at risk for poor outcome.

Application of fMRI to studies of cognitive development is of growing interest because of its sensitivity and non-invasive nature. However, interpretation of fMRI results in children is presently based on vascular dynamics that have been studied primarily in healthy adults. Comparison of the neurological basis of cognitive development is valid to the extent that the neurovascular responsiveness between children and adults is equal. The present study was designed to detect age-related vascular differences that may contribute to altered BOLD fMRI signal responsiveness. We examined BOLD signal changes in response to breath holding, a global, systemic state change in brain oxygenation. Children exhibited greater percent signal changes than adults in grey and white matter, and this was accompanied by an increase in noise. Consequently, the volume of activation exceeding statistical threshold was reduced in children. The reduced activation in children was well modeled by adding noise to adult data. These findings raise the possibility that developmental differences in fMRI findings between children and adults could, under some circumstances, reflect greater noise in the BOLD response in the brains of children than adults. BOLD responses varied across brain regions, but showed similar regional variation in children and adults.

Depression involves either enhanced processing of negative stimuli or diminished processing of positive stimuli. We used functional magnetic resonance imaging to assess brain activation in depressed vs healthy participants. Fifteen participants diagnosed with major depressive disorder and 15 controls were scanned during a lexical decision task involving neutral, happy, sad, and threat-related words. For happy words, depressed subjects exhibited less activation than did controls to happy words in fronto-temporal and limbic regions. For sad words, depressed subjects showed more activation than did controls in the inferior parietal lobule and less activation in the superior temporal gyrus and cerebellum, suggesting a complex activation pattern that varies for neural sub-circuits that may be associated with different cognitive or behavioral processes.

Acquisitions with the spiral-in/out technique result in two separate image timeseries obtained during the spiral-in and spiral-out trajectory. In uniform brain regions the two components have comparable signal and BOLD contrast and can be averaged, but in regions compromised by susceptibility effects where both signal and noise can differ in the two images other combination methods may be more effective. Here, several weighting schemes are compared for signal and activation contrast recovery in whole brain and prefrontal cortex using verbal working memory (seven subjects) and breathholding tasks (six subjects) scanned at 3 T. It was found that a statistically weighted combination based on activation maps derived separately from the spiral-in and spiral-out images provides activation volumes with increases of 33-59% over second-choice signal-weighted combination and 100-200% increases over spiral-out acquisition alone, and that simple averaging is inferior to signal-weighted combination.

Spiral-in/out functional magnetic resonance imaging (fMRI) methods acquire one image before the echo time (TE) and a second image after TE during each scan. Weighted combination of the two images provides a time series with reduced susceptibility dropout in frontal and medial temporal regions as well as increased signal-to-noise ratio (SNR) in regions of uniform cortex. In this study, task activation with the spiral-in/out method was compared to that with conventional spiral-out acquisitions at two field strengths (1.5 and 3.0 T) using episodic memory encoding, verbal working memory, and affective processing tasks in eight human volunteers. With the conventional spiral-out sequence, greater signal dropout is observed in lateral and medial prefrontal, amygdalar, and medial temporal regions at 3 T relative to 1.5 T, whereas such dropout at 3 T is reduced or mitigated with the spiral-in/out method. Similarly, activation volumes for frontal, amygdalar, and medial temporal regions are reduced for spiral-out acquisitions relative to spiral-in/out, and this difference is more apparent at 3 T than at 1.5 T. In addition, significant regionally specific increases in Z scores are obtained with the spiral-in/out sequence relative to spiral-out acquisitions at both field strengths. It is concluded the spiral-in/out sequence may provide significant advantages over conventional spiral methods, especially at 3 T.

Event-related fMRI was employed to characterize differences in brain activation between children ages 8-12 and adults related to two forms of cognitive control: interference suppression and response inhibition. Children were more susceptible to interference and less able to inhibit inappropriate responses than were adults. Effective interference suppression in children was associated with prefrontal activation in the opposite hemisphere relative to adults. In contrast, effective response inhibition in children was associated with activation of posterior, but not prefrontal, regions activated by adults. Children failed to activate a region in right ventrolateral prefrontal cortex that was recruited for both types of cognitive control by adults. Thus, children exhibited immature prefrontal activation that varied according to the type of cognitive control required.