Response anticipation and response conflict processes are supported by executive control. However, few neuroimaging studies have attempted to study the relationship between these two processes in the same experimental session. In this study, we isolated brain activity associated with response anticipation (after a cue to prepare vs relax) and with response conflict (responding to a target with incongruent vs congruent flankers) and examined the independence and interaction of brain networks supporting these processes using event-related potentials (ERPs) and functional magnetic resonance imaging. Response anticipation generated a contingent negative variation ERP that correlated with shorter reaction times, and was associated with activation of a thalamo-cortico-striatal network, as well as increased gamma band power in frontal and parietal regions, and decreased spectral power in theta, alpha, and beta bands in most regions. Response conflict was associated with increased activation in the anterior cingul...

We use a novel balanced experimental design to specifically investigate brain mechanisms underlying the modulating effect of expected pain intensity on afferent nociceptive processing and pain perception. We used two visual cues, each conditioned to one of two noxious thermal stimuli [∼48°C (high) or 47°C (low)]. The visual cues were presented just before and during application of the noxious thermal stimulus. Subjects reported significantly higher pain when the noxious stimulus was preceded by the high-intensity visual cue. To control for expectancy effects, for one-half of the runs, the noxious thermal stimuli were accompanied by the cue conditioned to the other stimulus. Comparing functional magnetic resonance imaging blood oxygenation level-dependent activations produced by the high and low thermal stimulus intensities presented with the high-intensity visual cue showed significant activations in nociceptive regions of the thalamus, second somatosensory cortex, and insular cortex. To isolate the effect...

Structural changes in both axon and myelin are observed in white matter injuries and have significant impact on the long-term disability of patients. In these disorders, clinical manifestations are not sufficient to determine the structural basis for neurological dysfunction and no convenient noninvasive biological markers to distinguish between myelin and axonal injury. Here we describe the use of in vivo quantitative MRI to quantify the transverse relaxation time (T2) in brains of shiverer mice lacking myelin and HM-DKO mice lacking neurofilaments. Shiverer mouse reduces myelin sheath formation in the CNS, and prevents glial-stimulated expansion of the calibers of axons without affecting neurofilament levels by electron microscope, Western blot, or immunocytochemistry. In HM-DKO, targeted disruption of heavy and medium subunits of neurofilaments drastically reduces light subunit and virtually eliminates neurofilaments from axons. The calibers of large myelinated axons are markedly reduced but the thickne...

Aging is associated with an increased risk for stroke and enhanced injury with reperfusion, although the aging-specific mechanisms underlying these observations are not known. Stroke studies in aged (>20 month old) transgenic mice are needed to address these questions, including potential alterations in cerebral blood flow (CBF). The purpose of this study was to utilize perfusion MRI to determine the effects of hypoxia-ischemia (H/I) on cerebral blood volume (CBV) as a measure of CBF, as well as post-ischemic structural changes, in young (3 month) and aged (24 month) mice. Male C57Bl/6 mice were subjected to unilateral carotid artery ligation (isoflurane anesthesia), recovered 2 hours, injected ip with gadolinium pentate (10mmol/Kg), and positioned in a small bore 9.4 tesla vertical Brucker magnet for multiple whole brain T2 images. Following baseline, 8% O2/bal N2 was delivered to obtain H/I images as depicted below. Top panel are CBV maps with corresponding structural images below, ligated(ischemic) hemi...

In this study, a well established expectancy manipulation model was combined with a novel placebo intervention, a validated sham acupuncture needle, to investigate the brain network involved in placebo analgesia. Sixteen subjects completed the experiment. We found that after placebo acupuncture treatment, subjective pain rating reduction (pre minus post) on the placebo-treated side was significantly greater than on the control side. When we calculated the contrast that subtracts the functional magnetic resonance imaging (fMRI) signal difference between post-treatment and pretreatment during pain application on placebo side from the same difference on control side [e.g., placebo (post – pre) – control (post – pre)], significant differences were observed in the bilateral rostral anterior cingulate cortex (rACC), lateral prefrontal cortex, right anterior insula, supramarginal gyrus, and left inferior parietal lobule. The simple regression (correlation) analysis between each subject's fMRI signal difference of...

The ability to form episodic memories requires one to bind relations between aspects of events that unfold over time. Several neuroimaging studies have investigated the encoding of specific items in isolation, however little is known about the neural mechanisms that support the formation of associations between temporally distinct items. Here, we used event-related functional magnetic resonance imaging (fMRI) to investigate the neural mechanisms of relational binding and item-specific processing in working memory (WM), and the impact of these operations on subsequent long-term memory (LTM) formation. During scanning, subjects made decisions about pairs of words separated by a delay of 9 seconds. On each trial, they were instructed to make a perceptual judgment about the first word (S1). When the second word (S2) appeared, they were either prompted to make a semantic decision specific to S2 (item-specific trials) or to make a decision that required comparison of S2 and S1 (relational trials). After scanning...

Objective: Different from traditional histamine application, the length and intensity of itch sensation can be controlled with our newly developed electrical stimulation on human skin. fMRI was applied to investigate the neural underpinnings of itch sensation evoked with this new method. Methods: Fourteen healthy human subjects (6 females and 8 males, aged 29.4±3.0yr, mean±SD) participated in this study. Transcutaneous electrical stimulation of 50Hz frequency and 2-ms pulse length was applied through a thin electrode (0.1 x 7mm) to evoke itch, while stimulation of 100Hz and 0.2-ms through a round plate electrode (diameter 15mm) to evoke pain. Both electrodes were put on the volar surface of the wrist skin. The stimulus intensity was individually adjusted and fixed before starting fMRI imaging to provoke itch or pain with rating of 30% on a VAS-scale (0.13±0.06mA for itch, 2.43±0.27mA for pain, mean±SEM). On a 3-T MRI scanner, functional images were obtained with a gradient-echo, echo planar imaging sequenc...

Glucocorticoids are known for their slow-acting genomic effects as transcription factors binding to a soluble steroid receptor. However, there are many reports that glucocorticoids can have immediate effects on neuronal excitability in the hypothalamus and hippocampus of mammals. While the glucocorticoid membrane receptor that presumably mediates this electrical activity has eluded researchers the immediate elctrophysiological and behavioral effects of abrupt increases in plasma levels of stress hormones are undeniable and well documented. Functional MRI with 3D computational analysis in conscious animals provides a method for identifying those brain areas and neural networks sensitive to the abrupt rise in plasma glucocorticoids that occur during a stress response. Rats showed a dose dependent change in brain activity to iv injection of a soluble steroid complex of corticosterone and 2-hydroxypropyl-B-cyclodextrin (vehicle, 1, 2.5, 10 mg/kg). The highest dose resulted in plasma corticosterone levels of ap...

Recent neurophysiological findings from the monkey hippocampus showed dramatic changes in the firing rate of individual hippocampal cells as a function of learning new associations. To extend these findings to humans, we used blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to examine the patterns of brain activity during learning of an analogous associative task. We observed bilateral, monotonic increases in activity during learning not only in the hippocampus but also in the parahippocampal and right perirhinal cortices. In addition, activity related to simple novelty signals was observed throughout the medial temporal lobe (MTL) memory system and in several frontal regions. A contrasting pattern was observed in a frontoparietal network in which a high level of activity was sustained until the association was well learned, at which point the activity decreased to baseline. Thus, we found that associative learning in humans is accompanied by striking increases in BOLD ...

Our previous research has shown that the left prefrontal cortex and anterior medial temporal lobes (MTL) are important for the formation of successful associations. In this study, we used an identical encoding task to our earlier paradigm, which was scanned on a Siemens 3T, followed by a different post-scan test in order to compare successful encoding of items and associations. During encoding, 19 subjects (15 F/4M, mean age 24.15 +/- 3.25) were scanned on a GE 3T while viewing 455 novel face-name pairs. Post-scan, subjects viewed all 455 faces seen during encoding plus 200 distracter faces and made an old/new decision followed by a confidence rating. Subjects then chose which of two names was previously paired with the face and indicated their confidence level. Random effects group averages for fMRI data were generated in SPM2 and thresholded at p<0.005, 5 voxel extent. Analyses analogous to our previous study revealed a similar pattern of activation in the MTL and left prefrontal cortex related to the su...