Low-intensity focused ultrasound for cocaine use disorder: High resolution targeting of the human insula

低强度聚焦超声治疗可卡因使用障碍:人类脑岛的高分辨率靶向

基本信息

  • 批准号:
    10669693
  • 负责人:
  • 金额:
    $ 59.48万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-08-01 至 2024-07-31
  • 项目状态:
    已结题

项目摘要

ABSTRACT Cocaine use disorder (CUD) is a chronic relapsing disorder with significant burden to society costing more than $85 billion per year globally and there is no US Food and Drug Administration-approved intervention. There is a critical need to develop effective new treatment strategies. One rapidly emerging potential therapeutic is neuromodulation using low-intensity focused ultrasound (LIFU). The enormous potential of LIFU stems from the ability to focus ultrasound through the intact skull to a millimeter-sized focal spot size anywhere in the brain. This makes it a powerful alternative to both invasive neurosurgical procedures and other noninvasive brain stimulation techniques that have limited spatial resolution and can only reach superficial areas of the brain. One promising target to treat cocaine use disorder (CUD) is the dorsal anterior insular cortex (dAI). Unfortunately, the dAI lies deep within the lateral sulcus covered by the overlying opercula of the temporal lobe and is not accessible with conventional noninvasive neuromodulatory techniques. As such, LIFU provides a potentially transformative methods to non-invasively modulate the dAI to reduce cocaine craving and addiction. The dAI is a critical brain region which is activated in the response to drug cue exposure and its extent of activation is positively correlated with self-reported craving in human studies. In small animal models, reversible inactivation of dorsal anterior insula reduces cocaine seeking, decreases relapse after voluntary abstinence and decreases cue-induced and context-induced reinstatement of cocaine seeking. Remarkably, humans with damage to the insula were able to stop smoking easily and without experiencing cravings or relapse. In addition, the dAI is part of the salience network (SN). The SN is implicated in the direction of attention toward important stimuli and integration of top- down appraisal and bottom-up visceral and sensory information. Models posit the dAI first assesses the emotional value of incoming stimuli before transmitting the information to other nodes to plan and initiate future goal directed actions. In addiction this network is dysfunctional leading to a disproportionate saliency and sensitivity to drug related cues that biases decision making to use and ultimately abuse. To advance LIFU as a potential therapeutic for the treatment of CUD, in the UG3 phase of this proposal we will first test the safety and tolerability of the intervention and examine how selective inhibition of dAI reduces its activity to affect cue-induced craving. Develop. Upon successful completion of the UG3 phase, the UH3 phase will build upon these findings by examining the effect of dose and the duration of effect as well as how LIFU to dAI affects whole-brain network dynamics as how this affects craving for cocaine. The application of this information will provide a fundamental break-through in understanding how ultrasound energy can be rationally deployed to produce predictable clinical effects and act as a catalyst for the widespread clinical adoption of this technology for the treatment of CUD as well as other forms of substance use disorder.
摘要

项目成果

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NASSIMA AIT-DAOUD其他文献

NASSIMA AIT-DAOUD的其他文献

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{{ truncateString('NASSIMA AIT-DAOUD', 18)}}的其他基金

1/2-Pharmacogenetic Treatments for Alcoholism
1/2-酒精中毒的药物遗传学治疗
  • 批准号:
    8273389
  • 财政年份:
    2012
  • 资助金额:
    $ 59.48万
  • 项目类别:
1/2-Pharmacogenetic Treatments for Alcoholism
1/2-酒精中毒的药物遗传学治疗
  • 批准号:
    8460484
  • 财政年份:
    2012
  • 资助金额:
    $ 59.48万
  • 项目类别:
New Pharmacotherapy for Alcohol and Co-morbid Disorders
酒精和共病疾病的新药物疗法
  • 批准号:
    8318743
  • 财政年份:
    2010
  • 资助金额:
    $ 59.48万
  • 项目类别:
New Pharmacotherapy for Alcohol and Co-morbid Disorders
酒精和共病疾病的新药物疗法
  • 批准号:
    8520114
  • 财政年份:
    2010
  • 资助金额:
    $ 59.48万
  • 项目类别:
New Pharmacotherapy for Alcohol and Co-morbid Disorders
酒精和共病疾病的新药物疗法
  • 批准号:
    8139054
  • 财政年份:
    2010
  • 资助金额:
    $ 59.48万
  • 项目类别:
New Pharmacotherapy for Alcohol and Co-morbid Disorders
酒精和共病疾病的新药物疗法
  • 批准号:
    7949511
  • 财政年份:
    2010
  • 资助金额:
    $ 59.48万
  • 项目类别:
New Medication Treatments for Stimulant Dependence
治疗兴奋剂依赖的新药物治疗
  • 批准号:
    8013349
  • 财政年份:
    2007
  • 资助金额:
    $ 59.48万
  • 项目类别:
New Medication Treatments for Stimulant Dependence
治疗兴奋剂依赖的新药物治疗
  • 批准号:
    7313772
  • 财政年份:
    2007
  • 资助金额:
    $ 59.48万
  • 项目类别:
New Medication Treatments for Stimulant Dependence
治疗兴奋剂依赖的新药物治疗
  • 批准号:
    8210949
  • 财政年份:
    2007
  • 资助金额:
    $ 59.48万
  • 项目类别:
New Medication Treatments for Stimulant Dependence
治疗兴奋剂依赖的新药物治疗
  • 批准号:
    7751305
  • 财政年份:
    2007
  • 资助金额:
    $ 59.48万
  • 项目类别:

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成瘾行为中谷氨酸稳态的神经元调节
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  • 批准号:
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  • 财政年份:
    2014
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Beta-arrestin Regulation of Ghrelin Signaling in Modulating Addictive Behavior
β-抑制素对 Ghrelin 信号传导在调节成瘾行为中的调节
  • 批准号:
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  • 财政年份:
    2014
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食欲素和瘦素对 VTA 中进食和成瘾行为的调节
  • 批准号:
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  • 财政年份:
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食欲素和瘦素对 VTA 中进食和成瘾行为的调节
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  • 财政年份:
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食欲素和瘦素对 VTA 中进食和成瘾行为的调节
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食欲素和瘦素对 VTA 中进食和成瘾行为的调节
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    7290942
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