Assessment of dynamic susceptibility contrast cerebral blood flow response to amphetamine challenge: A human pharmacological magnetic resonance imaging study at 1.5 and 4 T

Pharmacological MRI (phMRI) techniques can be used to monitor the neurophysiological effects of central nervous system (CNS) active drugs. In this study, we investigated whether dynamic susceptibility contrast (DSC) perfusion imaging employing the use of superparamagnetic iron oxide nanoparticles (Resovist) could be used to measure hemodynamic response to d-amphetamine challenge in human subjects at both 1.5 and 4 T. Significant changes in cerebral blood flow (CBF) were found in focal regions associated with the nigrostriatal circuit and mesolimbic and mesocortical dopaminergic pathways. More significant CBF responses were found at higher field strength, mainly within striatal structures. The results from this study indicate that DSC perfusion imaging using Resovist can be used to assess the efficacy of CNS-active drugs and may play a role in the development of novel psychiatric therapies at the preclinical level. © 2005 Wiley-Liss, Inc.

Modeling of the hemodynamic responses in block design fMRI studies

The hemodynamic response function (HRF) describes the local response of brain vasculature to functional activation. Accurate HRF modeling enables the investigation of cerebral blood flow regulation and improves our ability to interpret fMRI results. Block designs have been used extensively as fMRI paradigms because detection power is maximized; however, block designs are not optimal for HRF parameter estimation. Here we assessed the utility of block design fMRI data for HRF modeling. The trueness (relative deviation), precision (relative uncertainty), and identifiability (goodness-of-fit) of different HRF models were examined and test-retest reproducibility of HRF parameter estimates was assessed using computer simulations and fMRI data from 82 healthy young adult twins acquired on two occasions 3 to 4 months apart. The effects of systematically varying attributes of the block design paradigm were also examined. In our comparison of five HRF models, the model comprising the sum of two gamma functions with six free parameters had greatest parameter accuracy and identifiability. Hemodynamic response function height and time to peak were highly reproducible between studies and width was moderately reproducible but the reproducibility of onset time was low. This study established the feasibility and test-retest reliability of estimating HRF parameters using data from block design fMRI studies.

Functional neuroanatomy of auditory mismatch processing : an event-related fMRI study of duration-deviant oddballs

This study was designed to identify the neural networks underlying automatic auditory deviance detection in 10 healthy subjects using functional magnetic resonance imaging. We measured blood oxygenation level-dependent contrasts derived from the comparison of blocks of stimuli presented as a series of standard tones (50 ms duration) alone versus blocks that contained rare duration-deviant tones (100 ms) that were interspersed among a series of frequent standard tones while subjects were watching a silent movie. Possible effects of scanner noise were assessed by a “no tone” condition. In line with previous positron emission tomography and EEG source modeling studies, we found temporal lobe and prefrontal cortical activation that was associated with auditory duration mismatch processing. Data were also analyzed employing an event-related hemodynamic response model, which confirmed activation in response to duration-deviant tones bilaterally in the superior temporal gyrus and prefrontally in the right inferior and middle frontal gyri. In line with previous electrophysiological reports, mismatch activation of these brain regions was significantly correlated with age. These findings suggest a close relationship of the event-related hemodynamic response pattern with the corresponding electrophysiological activity underlying the event-related “mismatch negativity” potential, a putative measure of auditory sensory memory.

Orthographic/phonological facilitation of naming responses in the picture-word task: An event-related fMRI study using overt vocal responding

In the picture-word interference task, naming responses are facilitated when a distractor word is orthographically and phonologically related to the depicted object as compared to an unrelated word. We used event-related functional magnetic resonance imaging (fMRI) to investigate the cerebral hemodynamic responses associated with this priming effect. Serial (or independent-stage) and interactive models of word production that explicitly account for picture-word interference effects assume that the locus of the effect is at the level of retrieving phonological codes, a role attributed recently to the left posterior superior temporal cortex (Wernicke's area). This assumption was tested by randomly presenting participants with trials from orthographically related and unrelated distractor conditions and acquiring image volumes coincident with the estimated peak hemodynamic response for each trial. Overt naming responses occurred in the absence of scanner noise, allowing reaction time data to be recorded. Analysis of this data confirmed the priming effect. Analysis of the fMRI data revealed blood oxygen level-dependent signal decreases in Wernicke's area and the right anterior temporal cortex, whereas signal increases were observed in the anterior cingulate, the right orbitomedial prefrontal, somatosensory, and inferior parietal cortices, and the occipital lobe. The results are interpreted as supporting the locus for the facilitation effect as assumed by both classes of theoretical model of word production. In addition, our results raise the possibilities that, counterintuitively, picture-word interference might be increased by the presentation of orthographically related distractors, due to competition introduced by activation of phonologically related word forms, and that this competition requires inhibitory processes to be resolved. The priming effect is therefore viewed as being sufficient to offset the increased interference. We conclude that information from functional imaging studies might be useful for constraining theoretical models of word production.

The semantic interference effect in the picture-word paradigm: An event-related fMRI study employing overt responses

We used event-related functional magnetic resonance imaging (fMRI) to investigate neural responses associated with the semantic interference (SI) effect in the picture-word task. Independent stage models of word production assume that the locus of the SI effect is at the conceptual processing level (Levelt et al. [1999]: Behav Brain Sci 22:1-75), whereas interactive models postulate that it occurs at phonological retrieval (Starreveld and La Heij [1996]: J Exp Psychol Learn Mem Cogn 22:896-918). In both types of model resolution of the SI effect occurs as a result of competitive, spreading activation without the involvement of inhibitory links. These assumptions were tested by randomly presenting participants with trials from semantically-related and lexical control distractor conditions and acquiring image volumes coincident with the estimated peak hemodynamic response for each trial. Overt vocalization of picture names occurred in the absence of scanner noise, allowing reaction time (RT) data to be collected. Analysis of the RT data confirmed the SI effect. Regions showing differential hemodynamic responses during the SI effect included the left mid section of the middle temporal gyrus, left posterior superior temporal gyrus, left anterior cingulate cortex, and bilateral orbitomedial prefrontal cortex. Additional responses were observed in the frontal eye fields, left inferior parietal lobule, and right anterior temporal and occipital cortex. The results are interpreted as indirectly supporting interactive models that allow spreading activation between both conceptual processing and phonological retrieval levels of word production. In addition, the data confirm that selective attention/response suppression has a role in resolving the SI effect similar to the way in which Stroop interference is resolved. We conclude that neuroimaging studies can provide information about the neuroanatomical organization of the lexical system that may prove useful for constraining theoretical models of word production.

Functional localization of the human color center by decreased water displacement using diffusion-weighted fMRI

Introduction Decreased water displacement following increased neural activity has been observed using diffusion-weighted functional MRI (DfMRI) at high b-values. The physiological mechanisms underlying the diffusion signal change may be unique from the standard blood oxygenation level-dependent (BOLD) contrast and closer to the source of neural activity. Whether DfMRI reflects neural activity more directly than BOLD outside the primary cerebral regions remains unclear. Methods Colored and achromatic Mondrian visual stimuli were statistically contrasted to functionally localize the human color center Area V4 in neurologically intact adults. Spatial and temporal properties of DfMRI and BOLD activation were examined across regions of the visual cortex. Results At the individual level, DfMRI activation patterns showed greater spatial specificity to V4 than BOLD. The BOLD activation patterns were more prominent in the primary visual cortex than DfMRI, where activation was localized to the ventral temporal lobe. Temporally, the diffusion signal change in V4 and V1 both preceded the corresponding hemodynamic response, however the early diffusion signal change was more evident in V1. Conclusions DfMRI may be of use in imaging applications implementing cognitive subtraction paradigms, and where highly precise individual functional localization is required.