Development of MRI Techniques for Drug-Abuse Applications

药物滥用领域 MRI 技术的发展

• 批准号: 10699647
• 负责人: Yihong Yang
• 金额: $ 173.2万
• 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/10699647
• 关键词: Adult; Affect; African American; Age; Aging; Alcohol abuse; Alcohol consumption; American; Area; Behavior; Behavioral; Biological Markers; Brain; Brain region; Characteristics; Chronology; Clinic; Cocaine Users; Communities; Computer software; Contralateral; Data; Development; Dose; Double-Blind Method; Drug Addiction; Drug abuse; Enrollment; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Hamilton Rating Scale for Depression; Handedness; Health; Individual; Interval training; Journals; Left; Linear Models; Magnetic Resonance Imaging; Major Depressive Disorder; Mental Depression; Methods; Modeling; Morphine; Nature; Neurobiology; Neurosciences; Opioid; Outcome; Paper; Pathway interactions; Patients; Performance; Prefrontal Cortex; Prognosis; Recurrent disease; Regression Analysis; Reporting; Research; Research Project Grants; Rest; Sample Size; Sampling; Seeds; Severities; Site; Substance Use Disorder; Techniques; Test Result; Testing; Thalamic structure; Therapeutic Effect; Time; Trail Making Test; Training; Translations; Treatment Efficacy; Treatment Protocols; Treatment outcome; Urine; Validation; Visual; Work; addiction; aging brain; alcohol measurement; analog; base; brain based; brain behavior; cardiovascular risk factor; clinical practice; clinically significant; cognitive enhancement; cognitive function; cognitive neuroscience; cognitive performance; cohort; comorbidity; craving; dementia risk; depressive symptoms; design; disorder subtype; drinking; follow-up; frontier; heroin use; imaging biomarker; improved; independent component analysis; indexing; individualized medicine; male; methadone treatment; nervous system disorder; neuroimaging; neuromechanism; neuropsychiatry; neuroregulation; noninvasive brain stimulation; opioid use disorder; outcome prediction; placebo group; predictive modeling; premature; psychosocial; relapse prediction; repetitive transcranial magnetic stimulation; social; spectroscopic imaging; treatment effect; treatment program; treatment response; treatment-resistant depression; urinary; volunteer

1. Cox regression based modeling of functional connectivity and treatment outcome for relapse prediction and disease subtyping in substance use disorder Functional magnetic resonance imaging (fMRI) has become one of the most widely used noninvasive neuroimaging technique in research of cognitive neurosciences and of neural mechanisms of neuropsychiatric/neurological diseases. A primary goal of fMRI-based neuroimaging studies is to identify biomarkers for brain-behavior relationship and ultimately perform individualized treatment outcome prognosis. However, the concern of inadequate validation and the nature of small sample sizes are associated with fMRI-based neuroimaging studies, both of which hinder the translation from scientific findings to clinical practice. Therefore, the current paper presents a modeling approach to predict time-dependent prognosis with fMRI-based brain metrics and follow-up data. This prediction modeling is a combination of seed-based functional connectivity and voxel-wise Cox regression analysis with built-in nested cross-validation, which has been demonstrated to be able to provide robust and unbiased model performance estimates. Demonstrated with a cohort of treatment-seeking cocaine users from psychosocial treatment programs with 6-month follow-up, our proposed modeling method is capable of identifying brain regions and related functional circuits that are predictive of certain follow-up behavior, which could provide mechanistic understanding of neuropsychiatric/neurological disease and clearly shows neuromodulation implications and can be used for individualized prognosis and treatment protocol design (Zhai et al., Frontiers Neuroscience, 2021). 2. Dose-dependent relationship between social drinking and brain aging Low-level alcohol consumption is commonly perceived as being inconsequential or even beneficial for overall health, with some reports suggesting that it may protect against dementia or cardiovascular risks. However, these potential benefits do not preclude the concurrent possibility of negative health outcomes related to alcohol consumption. To examine whether casual, non-heavy drinking is associated with premature brain aging, we utilized the Brain-Age Regression Analysis and Computational Utility Software package to predict brain age in a community sample of adults n = 240, mean age 35.1 (10.7) years, 48% male, 49% African American. Accelerated brain aging was operationalized as the difference between predicted and chronological age ("brain age gap"). Multiple regression analysis revealed a significant association between previous 90-day alcohol consumption and brain age gap ( = 0.014, p = 0.023). We replicated these results in an independent cohort n = 231 adults, mean age 34.3 (11.1) years, 55% male, 28% African American: = 0.014, p = 0.002. Our results suggest that even low-level alcohol consumption is associated with premature brain aging. The clinical significance of these findings remains to be investigated (Angebrandt et al., Neurobiology of Aging). 3. Repetitive transcranial magnetic stimulation may reduce craving, depression and enhance cognitive performance in patients with opioid use disorder Opioid use disorder (OUD), often comorbid with depressive symptoms, causes substantial health and social burdens. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation method that used to treat depression. Recent studies showed potential therapeutic effects in rTMS for addictive disorder, but with limited studies in OUD. Therefore, we conducted an add-on double-blinded, sham-controlled rTMS study in OUD patients undergoing methadone maintenance therapy (MMT) to evaluate the treatment effect for heroin use. OUD patients were enrolled from MMT clinics. The active or sham rTMS treatment was applied to the left dorsolateral prefrontal cortex (DLPFC) (15 Hz frequency, 4 seconds per train, inter-train interval of 26 seconds, 40 trains per session, total 11 sessions in 4 weeks). The craving scales of Visual analog scale (VAS), Hamilton Depression Rating Scale (HDRS), Opiate Treatment Index (OTI), urinary morphine tests and cognitive functions were followed up for 12 weeks. Twenty-one OUD patients were enrolled, eleven were on active rTMS and eight were on sham rTMS. There was no significant difference in their baseline characteristics between the two groups. After 12 weeks, VAS and HDRS were significantly decreased in the active rTMS group (P=0.009 and <0.001). Trail Making Test Parts (TMT)-A and -B were also improved in the active rTMS group (P=0.01 and 0.02). Some factors at baseline, including HDRS scores and baseline TMT-B, were correlated to rTMS treatment outcomes. However, the active rTMS group did not show significantly greater improvements than the sham group in OTI or urine morphine test results. Our initial evidence suggested add-on rTMS in MMT may reduce the severity of craving, ameliorate depressive symptoms and improve some cognitive functions in OUD patients. However, further enlargement of sample size is required to evaluate the treatment response of rTMS in heroin use frequency and amount (Tsai et al., American Journal of Drug and Alcohol Abuse, 2021). 4. Low-frequency repetitive transcranial magnetic stimulation to the right dorsolateral prefrontal cortex The positive treatment outcomes of low frequency (LF) repetitive transcranial magnetic stimulation (rTMS) when applied over the right dorsolateral prefrontal cortex (DLPFC) in treatment-refractory depression has been verified. However, the mechanism of action behind these results have not been well explored. In this work we used simultaneous functional magnetic resonance imaging (fMRI) during TMS to explore the effect of LF rTMS on brain activity when applied to the right RDLPFC1 (MNI: 50, 30, 36) and left DLPFC sites LDLPFC1 (MNI: -50, 30, 36), LDLPFC2 (MNI: -41, 16, 54). Seventeen healthy adult volunteers participated in this study. To identify brain areas affected by rTMS, an independent component analysis and a general linear model were used. Our results showed an important laterality effect when contrasting rTMS over the left and right sites. Specifically, LF rTMS increased brain activity at the stratum, thalamus and areas of the default mode network when applied to the right, but not to the contralateral left DLPFC. In contrast, no site differences were observed when evaluating the effect of LF rTMS over the two left sites. These findings demonstrate that LF rTMS to the right DLPFC was able to stimulate the cortico-striato-thalamo-cortical pathway, which is dysregulated in patients with major depressive disorder; therefore, justifying the successful outcomes found thus far for LF rTMS in the treatment of depression (under review).

1. 基于 Cox 回归的功能连接和治疗结果建模，用于物质使用障碍的复发预测和疾病亚型分析 功能磁共振成像（fMRI）已成为认知神经科学研究和神经精神/神经系统疾病的神经机制中应用最广泛的无创神经影像技术之一。基于功能磁共振成像的神经影像研究的主要目标是识别大脑行为关系的生物标志物，并最终进行个体化治疗结果预测。然而，基于功能磁共振成像的神经影像研究存在验证不足和小样本的问题，这两者都阻碍了科学发现到临床实践的转化。因此，本文提出了一种建模方法，通过基于功能磁共振成像的大脑指标和后续数据来预测时间依赖性预后。该预测模型结合了基于种子的功能连接和体素方面的 Cox 回归分析以及内置嵌套交叉验证，已被证明能够提供稳健且无偏差的模型性能估计。通过对来自心理社会治疗项目的一组寻求治疗的可卡因使用者进行 6 个月的随访，我们提出的建模方法能够识别可预测某些后续行为的大脑区域和相关功能回路，这可以提供对神经精神/神经系统疾病的机械理解，并清楚地显示神经调节影响，并可用于个体化预后和治疗方案设计（Zhai 等人，Frontiers） 神经科学，2021）。 2. 社交饮酒与大脑衰老之间的剂量依赖性关系 低度饮酒通常被认为对整体健康无关紧要甚至有益，一些报告表明它可以预防痴呆或心血管风险。然而，这些潜在的好处并不能排除与饮酒相关的负面健康结果的可能性。为了研究偶然、非大量饮酒是否与大脑过早衰老有关，我们利用脑年龄回归分析和计算实用软件包来预测社区成年人样本的大脑年龄，样本为 n = 240，平均年龄 35.1 (10.7) 岁，48% 为男性，49% 为非裔美国人。大脑加速老化被操作化为预测年龄和实际年龄之间的差异（“大脑年龄差距”）。多元回归分析显示，之前 90 天的饮酒量与大脑年龄差距之间存在显着相关性 (= 0.014，p = 0.023)。我们在一个独立队列中重复了这些结果，n = 231 名成年人，平均年龄 34.3 (11.1) 岁，55% 男性，28% 非洲裔美国人：= 0.014，p = 0.002。我们的研究结果表明，即使是少量饮酒也与大脑过早衰老有关。这些发现的临床意义仍有待研究（Angebrandt 等人，《衰老神经生物学》）。 3. 重复经颅磁刺激可减少阿片类药物使用障碍患者的渴望、抑郁并增强认知能力 阿片类药物使用障碍 (OUD) 通常与抑郁症状共存，会造成巨大的健康和社会负担。重复经颅磁刺激（rTMS）是一种用于治疗抑郁症的无创脑刺激方法。最近的研究表明 rTMS 对成瘾性疾病具有潜在的治疗作用，但 OUD 的研究有限。因此，我们对接受美沙酮维持治疗（MMT）的 OUD 患者进行了一项附加双盲、假对照 rTMS 研究，以评估海洛因使用的治疗效果。 OUD 患者是从 MMT 诊所招募的。将主动或假 rTMS 治疗应用于左背外侧前额叶皮层 (DLPFC)（频率 15 Hz，每次训练 4 秒，训练间间隔 26 秒，每次训练 40 次，4 周内总共 11 次）。随访12周的视觉模拟量表(VAS)、汉密尔顿抑郁评定量表(HDRS)、阿片治疗指数(OTI)、尿吗啡测试和认知功能的渴望量表。共有 21 名 OUD 患者入组，其中 11 名接受主动 rTMS，8 名接受假 rTMS。两组之间的基线特征没有显着差异。 12周后，主动rTMS组的VAS和HDRS显着降低（P=0.009和<0.001）。主动 rTMS 组的越野测试部件 (TMT)-A 和 -B 也得到改善（P=0.01 和 0.02）。一些基线因素，包括 HDRS 评分和基线 TMT-B，与 rTMS 治疗结果相关。然而，活性 rTMS 组在 OTI 或尿液吗啡测试结果方面并未显示出比假手术组显着更大的改善。我们的初步证据表明，在 MMT 中添加 rTMS 可能会降低 OUD 患者渴望的严重程度、改善抑郁症状并改善某些认知功能。然而，需要进一步扩大样本量来评估 rTMS 对海洛因使用频率和用量的治疗反应（Tsai 等人，美国药物和酒精滥用杂志，2021）。 4. 对右侧背外侧前额叶皮层进行低频重复经颅磁刺激 低频（LF）重复经颅磁刺激（rTMS）应用于右背外侧前额叶皮层（DLPFC）治疗难治性抑郁症的积极治疗效果已得到验证。然而，这些结果背后的作用机制尚未得到很好的探索。在这项工作中，我们在 TMS 期间使用同步功能磁共振成像 (fMRI)，探讨 LF rTMS 应用于右侧 RDLPFC1 (MNI: 50, 30, 36) 和左侧 DLPFC 位点 LDLPFC1 (MNI: -50, 30, 36)、LDLPFC2 (MNI: -41, 16, 54) 时对大脑活动的影响。十七名健康成年志愿者参与了这项研究。为了识别受 rTMS 影响的大脑区域，使用了独立成分分析和一般线性模型。我们的结果显示，在对比左右部位的 rTMS 时，存在重要的偏侧效应。具体来说，当 LF rTMS 应用于右侧时，会增加层、丘脑和默认模式网络区域的大脑活动，但不会影响对侧的左侧 DLPFC。相反，在评估 LF rTMS 对左侧两个位点的影响时，没有观察到位点差异。这些发现表明，右 DLPFC 的 LF rTMS 能够刺激皮质-纹状体-丘脑-皮质通路，该通路在重度抑郁症患者中失调；因此，证明了迄今为止发现的 LF rTMS 在抑郁症治疗中取得的成功结果（正在审查中）。