Development of MRI Techniques for Drug-Abuse Applications

药物滥用领域 MRI 技术的发展

• 批准号: 8553243
• 负责人: Yihong Yang
• 金额: $ 101.83万
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8553243
• 关键词: Amygdaloid structure; Anisotropy; Anterior; Area; Back; Bilateral; Brain; Brain Part; Brain region; Cerebellum; Cerebrovascular Circulation; Cerebrum; Chronic; Cocaine; Cocaine Dependence; Cocaine Users; Corpus striatum structure; DSM-IV; Dependency; Detection; Development; Diffusion Magnetic Resonance Imaging; Dorsal; Drug abuse; Fiber; Functional Magnetic Resonance Imaging; Functional disorder; Glutamates; Glutamine; Goals; Graph; Hippocampus (Brain); Imaging Techniques; Inferior; Informal Social Control; Insula of Reil; Intervention; Lateral; Lead; Lobule; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Medial; Mediating; Mediation; Mediator of activation protein; Meditation; Mental disorders; Metabolic; Metabolism; Methods; Middle frontal gyrus structure; Modeling; Moods; Motor; Myelin; Neuronal Plasticity; Neurons; Neurotransmitters; Oxygen Consumption; Parietal; Pattern; Pharmaceutical Preparations; Precentral gyrus; Prefrontal Cortex; Publishing; Radial; Rattus; Relaxation Therapy; Reporting; Research Project Grants; Rest; Seeds; Short-Term Memory; Signal Transduction; Spectrum Analysis; Stimulus; Structure of inferior temporal gyrus; Techniques; Temporal Lobe; Thalamic structure; Time; Tissues; Training; Ventral Striatum; Work; area striata; base; blood oxygen level dependent; blood oxygenation level dependent response; body-mind; cingulate cortex; cocaine use; density; follow-up; gamma-Aminobutyric Acid; human data; image registration; improved; meetings; mindfulness meditation; morphometry; novel; prevent; putamen; receptor; response; spatiotemporal; theories; visual stimulus; white matter; white matter change

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)

1. 可卡因使用者皮质纹状体网络的结构和功能改变 使用基于体素的形态测定法（VBM）评估可卡因使用者的皮质与纹状体体积比。在 66 名可卡因依赖者的前扣带回和后扣带回 (ACC/PCC)、双侧岛叶、颞中叶、背外侧额叶 (dlPFC) 和后/中央回回中发现，符合 DSM-IV-TR 标准的数量与皮质纹状体比率之间存在显着负相关。这些区域的平均皮质纹状体比率可预测可卡因依赖性（R2=0.32，P<0.001）和当前可卡因的使用情况（R2=0.09，P<0.008），但不能预测可卡因使用的持续时间。 使用静息态功能磁共振成像评估可卡因使用者皮质纹状体网络的功能连接。将六颗种子放置在背侧和腹侧纹状体区域，并计算这些纹状体种子与皮质区域之间的功能连接。与健康对照组相比，可卡因组检测到背侧尾状核和背外侧前额叶之间的连接性增加，而背侧壳核和中扣带回 SMA 之间的连接性减少。皮质纹状体连接性的增加与目前可卡因的使用呈正相关。 （在 OHBM 年会上提出，2012 年） 2. 长期可卡因使用者大脑网络的图论分析 使用静息态功能磁共振成像，我们研究了长期可卡因使用者的功能性大脑网络中心的拓扑变化。具体来说，我们采用了中心性程度（衡量特定大脑区域与其他大脑区域之间连接数量的指标）来评估可卡因引起的众多中心性指标之间的差异。与健康对照组相比，可卡因使用者在 ACC、前岛叶和颞叶的中心度显着降低。后续分析显示，可卡因使用者的 ACC 与双侧岛叶、杏仁核和海马体之间的功能连接显着下降。同样，可卡因使用者的岛叶和 ACC 以及内侧 PFC 之间的功能连接也显着降低。 （在 OHBM 年会上提出，2012 年） 3. 基线 GABA 浓度预测功能连接强度 我们研究了 GABA 浓度与静息态大脑活动的关系，以及基线 GABA 浓度、静息功能连接和任务诱发的 BOLD fMRI 信号变化之间的相互作用。我们发现，静息 BOLD 波动的时空相关强度与初级视觉皮层静息 GABA 浓度呈负相关，两者都可以预测对视觉刺激引起的 BOLD 反应的幅度。中介分析表明，功能连接强度作为中介，在预测刺激诱发的 BOLD 信号变化方面具有显着的独特作用，并且当将静息相关强度添加到预测模型中时，GABA 浓度对 BOLD fMRI 响应的影响减小。研究表明，抑制 GABAA 受体介导的抑制会增加同步活动的传播以及大鼠的脑耗氧量，这可能会导致更高的相关强度。这项研究的结果可能有助于理解神经递质水平、内在大脑活动和诱发大脑激活之间的相互作用。 （在 ISMRM 年会上发表，2012 年） 4. 参数化 N-back 工作记忆任务中负载依赖的代谢活动 基于脑血流量（CBF）、血氧水平依赖性（BOLD）信号和脑氧合代谢率（CMRO2）的生物物理模型，我们在区域耗氧和代谢水平上检查了工作记忆任务诱导的活动。在额中回（MFG）、辅助运动区、顶下小叶、前岛叶、颞下回、丘脑和小脑中观察到基于 CMRO2 变化的任务诱导激活，而在后扣带皮层和内侧前额叶皮层中观察到任务失活。在 3-back 和 2-back 负载下观察到类似的任务激活和停用，而在 1-back 负载下则程度较小。显示 CMRO2 随任务负载线性增加/减少的区域与任务激活/停用重叠。在 MFG 和 IPL 中观察到 CMRO2 呈二次方增加。 CMRO2 和 CBF 在激活区域和受试者之间密切相关，并且不受激活、失活或任务负荷的影响。这项研究提供的证据表明，WM 任务诱导的激活、失活和负荷依赖性很可能源自大脑代谢，反映了神经元活动。 （在 OHBM 年会上提出，2012 年） 5. 冥想引起白质变化的机制 最近的几项研究表明，利用扩散张量成像，训练会导致白质效率的变化（通过分数各向异性 (FA) 来衡量）。在我们的工作中，我们发现一种正念冥想形式，即身心综合训练 (IBMT)，经过 4 周的训练后，前扣带皮层周围区域的 FA 改善程度高于接受放松训练的对照。径向扩散率（RD）的降低被解释为髓磷脂的改善，但轴向扩散率（AD）的降低涉及其他机制，例如轴突密度。我们现在报告说，经过 4 周的 IBMT 训练后，RD 和 AD 均下降，同时 FA 增加，这表明白质效率的提高涉及髓磷脂的增加以及其他轴突的变化。然而，两周的 IBMT 减少了 AD，但没有减少 RD 或 FA，并且改善了情绪。我们的结果证明了短期冥想中白质神经可塑性的时间过程。这种涉及前扣带皮层的白质变化的动态模式是与自我调节相关的大脑网络的一部分，可以提供一种改善或预防精神障碍的干预手段。 （与 Yiyuan Tang 和 Mike Posner 合作）（发表于 Proc Natl Acad Sci U S A，2012 年）