Yiping P. Du

Exposure to the Taste of Alcohol Elicits Activation of the Mesocorticolimbic Neurocircuitry

A growing number of imaging studies suggest that alcohol cues, mainly visual, elicit activation in mesocorticolimbic structures. Such findings are consistent with the growing recognition that these structures play an important role in the attribution of incentive salience and the pathophysiology of addiction. The present study investigated whether the presentation of alcohol taste cues can activate brain regions putatively involved in the acquisition and expression of incentive salience. Using functional magnetic resonance imaging, we recorded BOLD activity while delivering alcoholic tastes to 37 heavy drinking but otherwise healthy volunteers. The results yielded a pattern of BOLD activity in mesocorticolimbic structures (ie prefrontal cortex, striatum, ventral tegmental area/substantia nigra) relative to an appetitive control. Further analyses suggested strong connectivity between these structures during cue-elicited urge and demonstrated significant positive correlations with a measure of alcohol use problems (ie the Alcohol Use Disorders Identification Test). Thus, repeated exposure to the taste alcohol in the scanner elicits activation in mesocorticolimbic structures, and this activation is related to measures of urge and severity of alcohol problems.

Increased hemodynamic response in the hippocampus, thalamus and prefrontal cortex during abnormal sensory gating in schizophrenia ☆

OBJECTIVE Deficits in sensory gating are a common feature of schizophrenia. Failure of inhibitory gating mechanisms, shown by poor suppression of evoked responses to repeated auditory stimuli, has been previously studied using EEG methods. These methods yield information about the temporal characteristics of sensory gating deficits, but do not identify brain regions involved in the process. Hence, the neuroanatomical substrates of poor sensory gating in schizophrenia remain largely unknown. This study used functional magnetic resonance imaging (fMRI) to investigate the functional neuroanatomy of sensory gating deficits in schizophrenia. METHODS Twelve patients with schizophrenia and 12 healthy comparison subjects were scanned at 3 Tesla while performing a sensory gating task developed for fMRI. P50 EEG evoked potential recordings from a paired-stimulus conditioning-test paradigm were obtained from the same subjects. RESULTS Compared to healthy comparison subjects, patients with schizophrenia exhibited greater activation in the hippocampus, thalamus, and dorsolateral prefrontal cortex (DLPFC) during the fMRI sensory gating task. No group difference was observed in the superior temporal gyrus. Schizophrenia subjects also showed decreased P50 suppression as measured with EEG. Hemodynamic response in the fMRI measure was positively correlated with test/conditioning ratios from the EEG sensory gating measure. CONCLUSIONS Poor sensory gating in schizophrenia is associated with dysfunction of an apparent network of brain regions, including the hippocampus, thalamus and DLPFC. Greater activation of these regions is consistent with evidence for diminished inhibitory function in schizophrenia.

The relationship between vascular wall shear stress and flow-mediated dilation: endothelial function assessed by phase-contrast magnetic resonance angiography.

OBJECTIVES We sought: 1) to investigate the relationship between vascular wall shear stress and flow-mediated dilation (FMD) in humans, and 2) to investigate whether this relationship could explain why FMD is greater in small arteries. BACKGROUND Arterial wall shear stress (WSS) is considered to be the primary stimulus for the endothelial-dependent FMD response. However, the relationship between WSS and FMD has not been investigated in humans. Furthermore, FMD is greater in small arteries, though the reasons for this phenomenon are unclear. METHODS Using phase-contrast magnetic resonance angiography (PMRCA), we measured hyperemic WSS and FMD in 18 healthy volunteers. Peak systolic WSS was calculated assuming a blunted parabolic velocity profile. Diameter by PCMRA and by ultrasound was compared in nine subjects. RESULTS Flow-mediated dilation was linearly proportional to hyperemic peak systolic WSS (r = 0.79, p = 0.0001). Flow-mediated dilation was inversely related to baseline diameter (r = 0.62, p = 0.006), but the hyperemic peak WSS stimulus was also inversely related to baseline diameter (r = 0.47, p = 0.049). Phase-contrast magnetic resonance angiography and ultrasound diameters were compared in nine subjects and correlated well (r = 0.84, p < 0.0001), but diameter by PCMRA was greater (4.1 +/- 0.7 mm vs. 3.7 +/- 0.5 mm, p = 0.009). CONCLUSION Arterial FMD is linearly proportional to peak hyperemic WSS in normal subjects. Thus, the endothelial response is linearly proportional to the stimulus. Furthermore, the greater FMD response in small arteries is accounted for, at least partially, by a greater hyperemic WSS stimulus in small arteries. By allowing the calculation of vascular WSS, which is the stimulus for FMD, and by imaging a fixed arterial cross-section, thus reducing operator dependence, PCMRA enhances the assessment of vascular endothelial function.

In vivo multi-slice mapping of myelin water content using T2 * decay

Quantitative assessment of the myelin water content in the brain can substantially improve our understanding of white matter diseases such as multiple sclerosis. In this study, in vivo myelin water content was estimated using T(2)* relaxation with multi-slice acquisitions in magnetic resonance imaging (MRI). The main advantages of using T(2)* relaxation are (1) a low specific absorption rate (SAR), which is especially beneficial for imaging at high field strengths, (2) a short first-echo time (approximately 2 ms) and short echo spacing (approximately 1 ms), which allows for the acquisition of multiple sampling points during the fast decay of the myelin water signal, and (3) fast multi-slice acquisitions. High-resolution and multi-slice myelin water fraction (MWF) maps were obtained in a clinically acceptable scan time at 3T. Five healthy adults were scanned with a multi-gradient-echo sequence to acquire T(2)* signal decay data. Images with a dimension of 256x256 at eight slice locations were acquired in 8.5 min with a signal-to-noise ratio (SNR) of 94.8 in the first-echo images. The SNR was further increased by using an anisotropic diffusion filter. Local field gradients (LFG) were estimated from the acquired multi-slice data, and the LFG-induced signal decays were corrected with a first-order approximation of LFG using the sinc function. The corrected T(2)* signal decays were analyzed with a three-pool model to quantify MWF. Our results demonstrate the feasibility of in vivo multi-slice mapping of MWF using multi-compartmental analysis of the T(2)* signal decay.

Fast multislice mapping of the myelin water fraction using multicompartment analysis of T decay at 3T: A preliminary postmortem study†

Quantitative mapping of the myelin water content can provide significant insight into the pathophysiology of several white matter diseases, such as multiple sclerosis and leukoencephalopathies, and can potentially become a useful clinical tool for early diagnosis of these diseases. In this study, multicompartment analysis of T  2* decay (MCAT2*) was used for the quantitative mapping of myelin water fraction (MWF). T  2* decay of each voxel at multiple slice locations was acquired in fixed human brains using a multigradient‐echo (MGRE) pulse sequence with alternating readout gradient polarities. Compared to prior techniques using Carr‐Purcell‐Meiboom‐Gill (CPMG) acquisition, the MGRE acquisition approach has: 1) a very short first echo time (≈2 ms) and echo‐spacing (≈1 ms), which allows for the acquisition of multiple sampling points during the fast decay of the myelin water signal; 2) a low RF duty cycle, which is especially important for achieving acceptable specific absorption rate (SAR) levels at high field strengths. Multicompartment analysis was then applied to the T  2* decay in each pixel using a 3‐pool model of white matter to detect the signal arising from the myelin water, myelinated axonal water, and mixed water compartments. Magn Reson Med 58:865–870, 2007.

Risky Decisions and Their Consequences: Neural Processing by Boys with Antisocial Substance Disorder

Background Adolescents with conduct and substance problems (“Antisocial Substance Disorder” (ASD)) repeatedly engage in risky antisocial and drug-using behaviors. We hypothesized that, during processing of risky decisions and resulting rewards and punishments, brain activation would differ between abstinent ASD boys and comparison boys. Methodology/Principal Findings We compared 20 abstinent adolescent male patients in treatment for ASD with 20 community controls, examining rapid event-related blood-oxygen-level-dependent (BOLD) responses during functional magnetic resonance imaging. In 90 decision trials participants chose to make either a cautious response that earned one cent, or a risky response that would either gain 5 cents or lose 10 cents; odds of losing increased as the game progressed. We also examined those times when subjects experienced wins, or separately losses, from their risky choices. We contrasted decision trials against very similar comparison trials requiring no decisions, using whole-brain BOLD-response analyses of group differences, corrected for multiple comparisons. During decision-making ASD boys showed hypoactivation in numerous brain regions robustly activated by controls, including orbitofrontal and dorsolateral prefrontal cortices, anterior cingulate, basal ganglia, insula, amygdala, hippocampus, and cerebellum. While experiencing wins, ASD boys had significantly less activity than controls in anterior cingulate, temporal regions, and cerebellum, with more activity nowhere. During losses ASD boys had significantly more activity than controls in orbitofrontal cortex, dorsolateral prefrontal cortex, brain stem, and cerebellum, with less activity nowhere. Conclusions/Significance Adolescent boys with ASD had extensive neural hypoactivity during risky decision-making, coupled with decreased activity during reward and increased activity during loss. These neural patterns may underlie the dangerous, excessive, sustained risk-taking of such boys. The findings suggest that the dysphoria, reward insensitivity, and suppressed neural activity observed among older addicted persons also characterize youths early in the development of substance use disorders.

Attentional Control Activation Relates to Working Memory in Attention-Deficit/Hyperactivity Disorder

BACKGROUND Attentional control difficulties in individuals with attention-deficit/hyperactivity disorder (ADHD) might reflect poor working memory (WM) ability, especially because WM ability and attentional control rely on similar brain regions. The current study examined whether WM ability might explain group differences in brain activation between adults with ADHD and normal control subjects during attentional demand. METHODS Participants were 20 adults with ADHD combined subtype with no comorbid psychiatric or learning disorders and 23 control subjects similar in age, IQ, and gender. The WM measures were obtained from the Wechsler Adult Intelligence Scale-III and Wechsler Memory Scale-Revised. Brain activation was assessed with functional magnetic resonance imaging (fMRI) while performing a Color-Word Stroop task. RESULTS Group differences in WM ability explained a portion of the activation in left dorsolateral prefrontal cortex (DLPFC), which has been related to the creation and maintenance of an attentional set for task-relevant information. In addition, greater WM ability predicted increased activation of brain regions related to stimulus-driven attention and response selection processes in the ADHD group but not in the control group. CONCLUSIONS The inability to maintain an appropriate task set in young adults with combined type ADHD, associated with decreased activity in left DLPFC, might in part be due to poor WM ability. Furthermore, in individuals with ADHD, higher WM ability might relate to increased recruitment of stimulus-driven attention and response selection processes, perhaps as a compensatory strategy.

The neural basis of sustained and transient attentional control in young adults with ADHD.

Differences in neural activation during performance on an attentionally demanding Stroop task were examined between 23 young adults with ADHD carefully selected to not be co-morbid for other psychiatric disorders and 23 matched controls. A hybrid blocked/single-trial design allowed for examination of more sustained vs. more transient aspects of attentional control. Our results indicated neural dysregulation across a wide range of brain regions including those involved in overall arousal, top-down attentional control, response selection, and inhibition. Furthermore, this dysregulation was most notable in lateral regions of DLPFC for sustained attentional control and in medial areas for transient aspects of attentional control. Because of the careful selection and matching of our two groups, these results provide strong evidence that the neural systems of attentional control are dysregulated in young adults with ADHD and are similar to dysregulations seen in children and adolescents with ADHD.

Fast modelling of the collimator–detector response in Monte Carlo simulation of SPECT imaging using the angular response function

Interactions of incident photons with the collimator and detector, including septal penetration, scatter and x-ray fluorescence, are significant sources of image degradation in applications of SPECT including dual isotope imaging and imaging using radioisotopes that emit high- or medium-energy photons. Modelling these interactions using full Monte Carlo (MC) simulations is computationally very demanding. We present a new method based on the use of angular response functions (ARFs). The ARF is a function of the incident photons direction and energy and represents the probability that a photon will either interact with or pass through the collimator, and be detected at the intersection of the photons direction vector and the detection plane in an energy window of interest. The ARFs were pre-computed using full MC simulations of point sources that include propagation through the collimator-detector system. We have implemented the ARF method for use in conjunction with the SimSET/PHG MC code to provide fast modelling of both interactions in the patient and in the collimator-detector system. Validation results in the three cases studied show that there was good agreement between the projections generated using the ARF method and those from previously validated full MC simulations, but with hundred to thousand fold reductions in simulation time.

Reducing Susceptibility Artifacts in fMRI Using Volume- Selective z-Shim Compensation

Susceptibility‐induced magnetic field gradients (SFGs) can result in severe signal loss in the orbitofrontal cortex (OFC) in gradient‐echo‐based functional MRI (fMRI) studies. Although conventional z‐shim techniques can effectively recover the MRI signal in this region, the substantial penalty in imaging time hampers their use in routine fMRI studies. A modified z‐shim technique with high imaging efficiency is presented in this study. In this technique, z‐shim compensations are applied only to a selective volume where the susceptibility artifact is severe. The results of an fMRI study (N = 6) demonstrate the feasibility of detecting the OFC activation with z‐shim in whole‐brain fMRI studies at a temporal resolution of 2 s. Magn Reson Med 57:396–404, 2007.