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Mapping the neural circuit of credit assignment for a new targeted intervention in addiction

绘制信用分配的神经回路以进行新的有针对性的成瘾干预

基本信息

批准号：
MR/T023007/1
负责人：
Elsa Fouragnan
金额：
$ 105.06万
依托单位：
Plymouth University
依托单位国家：
英国
项目类别：
Fellowship
财政年份：
2020
资助国家：
英国
起止时间：
2020 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FT023007%2F1
关键词：
Mapping neural circuit credit assignment

项目摘要

Imagine that you cannot wear your lucky socks for an upcoming test. In the event of failure, will you blame your absent clothing or your lack of preparation? The ability to identify which actions cause a particular event to occur is called "credit assignment". This ability allows individuals to properly make decisions and learn from their mistakes.Problems with credit assignment are linked to various mental health conditions, like addiction and obsessive-compulsive-disorders where individuals continue to believe that their drug-taking or rituals will lead to positive outcomes [1]. However, clinicians tend to define and diagnose mental illnesses in terms of their clinical symptoms, not by their underlying psychological traits or biological abnormalities [2]. No-one has yet studied how changes in the brain lead to the problems of credit assignment that are seen in psychiatric disorders. Solving this riddle will help us understand how humans can work out cause and effect, as well as what happens when they lose this ability.My plan with this fellowship is to i) extract clinically-relevant traits that describe a person's ability - or lack thereof - for credit assignment from a large database, ii) map them onto brain mechanisms, and iii) restore the identified circuit dysfunction and therefore reduce the related maladaptive behaviours in patients suffering from addiction. To do so, I will, in a first stage, collect a large-scale dataset ("big-data") from an online study where participants will assign credit to distinct stimuli that predict a variety of events. Computational learning models will be used to explain this large dataset by teasing apart the hidden attentional and learning features of credit assignment [3-5] and relate them to various psychiatric dimensions. These will then be contrasted against neural data (acquired with fMRI while participants carry out the same credit assignment task). This will help map out the full neural circuitry involved in credit assignment and relate it to the phenotype of mental health issues. In the second stage of the fellowship, I plan to use a cutting-edge technique called ultrasound neurostimulation to target the different parts of the brain that cause pathological credit assignment and over-reliance on habits. Ultrasound neurostimulation is an early-stage, non-invasive therapeutic technology that has the potential to improve the lives of millions of patients with mental health conditions by stimulating brain tissues with millimetre accuracy [6]. My previous research has recently shown that ultrasound can safely modulate activity in deep brain areas in macaques to elicit precise behavioural changes [7]. Importantly, its safe use in humans has also been established [8-9]. In sum, ultrasound neurostimulation will be used to restore the brain regions involved in credit assignment and alleviate the corresponding negative symptoms in patients.This approach has the potential to help the nearly two million patients suffering from maladaptive addictive behavioural patterns by designing new stimulation paradigms that effectively restore brain function. Moreover, besides addictive disorders, ultrasound brain therapy could also be used to restore normal functioning of brain circuits involved in anxiety, mood disorders, and obsessive-compulsive disorders for which effective therapies are desperately needed.[1] Everitt &al. NatNeuro. 8,1481-1489(2005). [2] Hyman &al. NatRevNeuro. 8,725-732(2007). [3] Fouragnan &al. NatComm. 6,8107(2015). [4] Fouragnan &al. SciRep. 7,4762(2017). [5] Queirazza, Fouragnan &al. forthcoming at Science Advances (2019). [6] Aubry JoAcoustSocAm. 143,1731-1731 (2018). [7] Fouragnan &al. NatNeuro. 22,797-808(2019). [8] Fomenko &al. BrainStim. 11,1209-1217(2018). [9] Tsai &al. MedHypo. 84,381-383 (2015).

想象一下，你不能穿你的幸运袜为即将到来的测试。如果失败了，你会责怪你没有穿衣服还是你缺乏准备？识别哪些行为导致特定事件发生的能力称为“信用分配”。这种能力使个人能够正确地做出决定，并从错误中学习。信用分配问题与各种心理健康状况有关，如成瘾和强迫症，其中个人继续相信他们的吸毒或仪式会带来积极的结果[1]。然而，临床医生倾向于根据他们的临床症状来定义和诊断精神疾病，而不是根据他们潜在的心理特征或生物异常[2]。还没有人研究过大脑的变化是如何导致精神疾病中的信用分配问题的。解开这个谜题将有助于我们理解人类如何找出因果关系，以及当他们失去这种能力时会发生什么。我对这个奖学金的计划是：i）从一个大型数据库中提取与临床相关的特征，这些特征描述了一个人的能力-或缺乏能力-用于学分分配，ii）将它们映射到大脑机制上，以及iii）恢复所识别的回路功能障碍，从而减少患有成瘾的患者的相关适应不良行为。为此，我将在第一阶段从在线研究中收集大规模数据集（“大数据”），参与者将对预测各种事件的不同刺激进行评分。计算学习模型将被用来解释这个大型数据集，通过梳理学分分配的隐藏注意力和学习特征[3-5]，并将它们与各种精神病学维度联系起来。然后将这些数据与神经数据（在参与者执行相同的学分分配任务时通过fMRI获得）进行对比。这将有助于绘制出参与学分分配的完整神经回路，并将其与心理健康问题的表型联系起来。在研究的第二阶段，我计划使用一种名为超声波神经刺激的尖端技术，针对大脑中导致病态信用分配和过度依赖习惯的不同部位。超声神经刺激是一种早期的非侵入性治疗技术，通过以毫米精度刺激脑组织，有可能改善数百万精神健康患者的生活[6]。我之前的研究最近表明，超声波可以安全地调节猕猴脑深部区域的活动，以引起精确的行为变化[7]。重要的是，它在人类中的安全使用也已确定[8-9]。总之，超声神经刺激将用于恢复参与信用分配的大脑区域，并减轻患者相应的负面症状。这种方法有可能通过设计有效恢复大脑功能的新刺激模式来帮助近200万患有适应不良成瘾行为模式的患者。此外，除了成瘾性疾病，超声波脑治疗还可以用于恢复与焦虑，情绪障碍和强迫症有关的脑回路的正常功能，这些疾病迫切需要有效的治疗方法。[1]Everitt &al. NatNeuro. 8，1481 -1489（2005）。[2]Hyman等人，NatRevNeuro. 8，725 -732（2007）。[3]Fouragnan &al. NatComm. 6，8107（2015）。[4]Fouragnan等人，SciRep. 7，4762（2017）。[5]Queirazza，Fouragnan &al.即将在科学进展（2019）。[6]奥布里·乔·阿库斯特·萨卡姆143，1731 -1731（2018）。[7]Fouragnan &al. NatNeuro. 22，797 -808（2019）。[8]Fomenko等人，BrainStim. 11，1209 -1217（2018）。[9]Tsai等人MedHypo. 84，381 -383（2015）。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A Common Neural Account for Social and Nonsocial Decisions.

DOI：
10.1523/jneurosci.0375-22.2022
发表时间：
2022-11-30
期刊：
JOURNAL OF NEUROSCIENCE
影响因子：
5.3
作者：
Arabadzhiyska, Desislava H;Garrod, Oliver G B;Fouragnan, Elsa;De Luca, Emanuele;Schyns, Philippe G;Philiastides, Marios G
通讯作者：
Philiastides, Marios G

Ultrasound modulation of macaque prefrontal cortex selectively alters credit assignment-related activity and behavior.

DOI：
10.1126/sciadv.abg7700
发表时间：
2021-12-17
期刊：
Science advances
影响因子：
13.6
作者：
Folloni D;Fouragnan E;Wittmann MK;Roumazeilles L;Tankelevitch L;Verhagen L;Attali D;Aubry JF;Sallet J;Rushworth MFS
通讯作者：
Rushworth MFS

Three-layer model with absorption for conservative estimation of the maximum acoustic transmission coefficient through the human skull for transcranial ultrasound stimulation.

具有吸收功能的三层模型，用于保守估计经颅超声刺激通过人体颅骨的最大声传输系数。