Development of MRI Techniques for Drug-Abuse Applications

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1. Structural and functional alterations of corticostriatal networks in cocaine users Cortical-to-striatal volumetric ratio was assessed in cocaine users using voxel-based morphometry (VBM). Significant negative correlation between the number of DSM-IV-TR criteria met and corticostriatal ratio was found in 66 cocaine dependents in the anterior and posterior cingulate (ACC/PCC), bilateral insula, middle temporal, dorsal lateral frontal (dlPFC) and post/precentral gyri. Mean corticostriatal ratio in these regions predicts cocaine dependence (R2=0.32, P<0.001) and current use of cocaine (R2=0.09, P<0.008), but not the duration of cocaine use. Functional connectivity of the corticostriatal networks of cocaine users was assessed using resting-state fMRI. Six seeds were placed in dorsal and ventral striatum areas, and functional connectivity between these striatal seeds to the cortical regions was calculated. Compared to healthy controls, increased connectivity between dorsal caudate and dorsal lateral prefrontal and decreased connectivity between dorsal putamen and middle cingulate-SMA were detected in cocaine group. The increased corticostriatal connectivity was positively correlated with current use of cocaine. (Presented in the Annual Meeting of OHBM, 2012) 2. Graph-theory analyses of brain networks in chronic cocaine users Using resting-state fMRI, we investigated the topological changes in the centrality of functional brain networks in chronic cocaine users. Specifically, we employed degree centrality, which is a measure of the number of connections between a specific brain region and other brain regions, to assess cocaine-induced differences among numerous centrality measures. Compared with healthy countrols, cocaine users showed significant lower degree centrality in the ACC, anterior insula, and temporal lobe. A follow-up analysis revealed that functional connectivity, in cocaine users, between the ACC and bilateral insula, amygdala and hippocampus was significantly decreased. Similarly, functional connectivity between the insula and ACC and medial PFC was significantly decreased in cocaine users. (Presented in the Annual Meeting of OHBM, 2012) 3. Baseline GABA concentration predicts functional connectivity strength We investigated the relationship of GABA concentration and resting-state brain activity as well as the interplay of baseline GABA concentration, resting functional connectivity, and task-evoked BOLD fMRI signal change. We found that the spatiotemporal correlation strength of resting BOLD fluctuations is negatively correlated with resting GABA concentration in primary visual cortex, both of which can predict the amplitude of evoked BOLD responses to visual stimulus. The mediation analysis shows that the functional connectivity strength, acting as a mediator, has a significant unique effect in predicting the stimulus-evoked BOLD signal changes, and the effect of the GABA concentration on the BOLD fMRI responses reduces when the resting correlation strength was added into the prediction model. It has been shown that suppression of GABAA receptor-mediated inhibition increases the spread of synchronized activity, as well as the cerebral oxygen consumption in rats, which may lead to higher correlation strength. Findings in this study may help to understand the interplay of the neurotransmitter level, intrinsic brain activity and evoked brain activation. (Presented in the Annual Meeting of ISMRM, 2012) 4. Load dependent metabolic activity in parametric N-back working memory tasks Based on a biophysical model of cerebral blood flow (CBF), blood-oxygenation level dependent (BOLD) signal and cerebral metabolic rate of oxygenation (CMRO2), we examined working memory task induced activity at the level of regional oxygen consumption and metabolism. Task-induced activation based on CMRO2 changes was observed in the middle frontal gyrus (MFG), supplementary motor area, inferior parietal lobule, anterior insula, inferior temporal gyrus, thalamus and cerebellum, while task deactivation was observed in the posterior cingulate cortex and medial prefrontal cortex. Similar task activation and deactivation were observed under 3-back and 2-back loads, while with a less extent under 1-back load. The regions showing linear increases/decreases of CMRO2 with task loads were overlapped with task activation/deactivation. Quadratic increases of CMRO2 were observed in MFG and IPL. CMRO2 and CBF were closely related across the activated regions and across subjects, and unaffected by activation, deactivation or task load. This study provides evidence that the WM task-induced activation, deactivation and load dependency are likely originated from cerebral metabolism, re&#64258;ecting neuronal activity. (Presented in the Annual Meeting of OHBM, 2012) 5. Mechanisms of white matter changes induced by meditation Using diffusion tensor imaging, several recent studies have shown that training results in changes in white matter efficiency as measured by fractional anisotropy (FA). In our work, we found that a form of mindfulness meditation, integrative body-mind training (IBMT), improved FA in areas surrounding the anterior cingulate cortex after 4-week training more than controls given relaxation training. Reductions in radial diffusivity (RD) have been interpreted as improved myelin but reductions in axial diffusivity (AD) involve other mechanisms, such as axonal density. We now report that after 4-week training with IBMT, both RD and AD decrease accompanied by increased FA, indicating improved efficiency of white matter involves increased myelin as well as other axonal changes. However, 2-week IBMT reduced AD, but not RD or FA, and improved moods. Our results demonstrate the time-course of white matter neuroplasticity in short-term meditation. This dynamic pattern of white matter change involving the anterior cingulate cortex, a part of the brain network related to self-regulation, could provide a means for intervention to improve or prevent mental disorders. (Collaborated with Yiyuan Tang and Mike Posner) (Published in Proc Natl Acad Sci U S A, 2012)