Wolfgang Engelien

Differential Time Courses and Specificity of Amygdala Activity in Posttraumatic Stress Disorder Subjects and Normal Control Subjects

BACKGROUND Previous neuroimaging studies have demonstrated exaggerated amygdala responses to negative stimuli in posttraumatic stress disorder (PTSD). The time course of this amygdala response is largely unstudied and is relevant to questions of habituation and sensitization in PTSD exposure therapy. METHODS We applied blood oxygen level dependent functional magnetic resonance imaging and statistical parametric mapping to study amygdala responses to trauma-related and nontrauma-related emotional words in sexual/physical abuse PTSD and normal control subjects. We examined the time course of this response by separate analysis of early and late epochs. RESULTS PTSD versus normal control subjects have a relatively increased initial amygdala response to trauma-related negative, but not nontrauma-related negative, versus neutral stimuli. Patients also fail to show the normal patterns of sensitization and habituation to different categories of negative stimuli. These findings correlate with measured PTSD symptom severity. CONCLUSIONS Our results demonstrate differential time courses and specificity of amygdala response to emotional and control stimuli in PTSD and normal control subjects. This has implications for pathophysiologic models of PTSD and treatment response. The results also extend previous neuroimaging studies demonstrating relatively increased amygdala response in PTSD and expand these results to a largely female patient population probed with emotionally valenced words.

Transit time, trailing time, and cerebral blood flow during brain activation : Measurement using multislice, pulsed spin-labeling perfusion imaging

Transit time and trailing time in pulsed spin‐labeling perfusion imaging are likely to be modulated by local blood flow changes, such as those accompanying brain activation. The majority of transit/trailing time is due to the passage of the tagged blood bolus through the arteriole/capillary regions, because of lower blood flow velocity in these regions. Changes of transit/trailing time during activation could affect the quantification of CBF in functional neuroimaging studies, and are therefore important to characterize. In this work, the measurement of transit and trailing times and CBF during sensorimotor activation using multislice perfusion imaging with pulsed arterial spin‐labeling is described. While CBF elevated dramatically (∼︁80.7%) during the sensorimotor activation, sizable reductions of transit time (∼︁0.11 sec) and trailing time (∼︁0.26 sec) were observed. Transit and trailing times were dependent on the distances from the leading and trailing edges of the tagged blood bolus to the location of the imaging slices. The effects of transit/trailing time changes on CBF quantification during brain activation were analyzed by simulation studies. Significant errors can be caused in the estimation of CBF if such changes of transit/trailing time are not taken into account. Magn Reson Med 44:680–685, 2000.

A silent event-related functional MRI technique for brain activation studies without interference of scanner acoustic noise

A new data acquisition method for silent, event‐related functional MRI in which scanner acoustic noise does not interfere with brain activation is introduced and evaluated in an auditory tonotopic mapping experiment. This method takes into account the hemodynamic‐response characteristics of the brain during activation, associated with both task performance and scanner noise. A data acquisition scheme was designed to collect task‐induced brain activation signals without interference of scanner noise on stimulus delivery or on the measured response. The advantages of the technique were demonstrated in a tonotopic mapping experiment of human auditory cortex. Tonotopic maps obtained by the technique in normal subjects showed distinct spatial shifts of the activation foci in the lateral part of Heschls gyrus with changing stimulus frequency, whereas no systematic shift was shown in a conventional event‐related experiment using the same stimulation paradigm. Signal change in the activation foci with the new technique was 54% larger than with the conventional technique, suggesting an increased dynamic range of the signal change associated with task‐induced brain activation under silent conditions. Magn Reson Med 43:185–190, 2000.

A CBF-Based Event-Related Brain Activation Paradigm: Characterization of Impulse-Response Function and Comparison to BOLD

A perfusion-based event-related functional MRI method for the study of brain activation is presented. In this method, cerebral blood flow (CBF) was measured using a recently developed multislice arterial spin-labeling (ASL) perfusion imaging method with rapid spiral scanning. Temporal resolution of the perfusion measurement was substantially improved by employing intertrial subtraction and stimulus-shifting schemes. Perfusion and blood oxygenation level-dependent (BOLD) signals were obtained simultaneously by subtracting or adding the control and labeled images, respectively, in the same data sets. The impulse response function (IRF) of perfusion during brain activation was characterized for multiple stimulus durations and compared to the simultaneously acquired BOLD response. The CBF response curve preceded the BOLD curve by 0.21 s in the rising phase and 0.64 s in the falling phase. Linear additivity of the CBF and BOLD responses was assessed with rapidly repeated stimulations within single trials, and departure from linearity was found in both responses, characterized as attenuated amplitude and delayed rising time. Event-related visual and sensorimotor activation experiments were successfully performed with the new perfusion technique.

Physiological mapping of human auditory cortices with a silent event-related fMRI technique.

Cortical field boundaries of sensory areas can be physiologically defined. The delineation of the human auditory cortical architecture remains incomplete. Here we used systematic variation of pitch and duration of sinusoidal tones to define auditory cortical fields along Heschls gyrus with a silent, event-related fMRI scanning technique that allowed us to determine spatially small shifts of neuronal responses. Thus, we were able to establish higher-resolution tonotopic maps. Acoustic intervals of two octaves correspond to an average 2-mm anatomical distance along Heschls gyrus. We also demonstrate that one tonotopic map with a medio-lateral low- to high-frequency gradient is located on the lateral half of Heschls gyrus, which might correspond to field R in primates. Furthermore, we studied cortical responses to brief (50-ms) transients with fMRI and demonstrate that silent, event-related fMRI is capable of measuring significant blood oxygen level-dependent effect to such brief events in the acoustic domain. Our results add to current knowledge on the number and precise localization of multiple tonotopic maps in human auditory cortex. More specifically, they support the hypothesis that there may be two primary auditory cortical fields with mirror tonotopic organization on Heschls gyrus in man.

Mapping Transient, Randomly Occurring Neuropsychological Events Using Independent Component Analysis

The feasibility of mapping transient, randomly occurring neuropsychological events using independent component analysis (ICA) was evaluated in an auditory sentence-monitoring fMRI experiment, in which prerecorded short sentences of random content were presented in varying temporal patterns. The efficacy of ICA on fMRI data with such temporal characteristics was assessed by a series of simulation studies, as well as by human activation studies. The effects of contrast-to-noise ratio level, spatially varied hemodynamic response within a brain region, time lags of the responses among brain regions, and different simulated activation locations on the ICA were investigated in the simulations. Component maps obtained from the auditory sentence-monitoring experiments in each subject using ICA showed distinct activation in bilateral auditory and language cortices, as well as in superior sensorimotor cortices, consistent with previous PET studies. The associated time courses in the activated brain regions matched well to the timing of the sentence presentation, as evidenced by the recorded button-press response signals. Methods for ICA component ordering that may rank highly the components of primary interest in such experiments were developed. The simulation results characterized the performance of ICA under various conditions and may provide useful information for experimental design and data interpretation.

The Parahippocampal Region and Auditory‐Mnemonic Processing

A. ENGELIEN,a,b E. STERN,b N. ISENBERG,b,d W. ENGELIEN,b C. FRITH,c AND D. SILBERSWEIGb bFunctional Neuroimaging Laboratory, Weill Medical College of Cornell University, 525 East 68th Street, New York, New York 10021, USA cWellcome Department of Cognitive Neurology, Institute of Neurology, University College London, 12 Queen Square, London WC1N 3BG, UK dNew Jersey Neuroscience Institute, JFK Medical Center, 65 James Street, Edison, New Jersey 08818, USA