Integrative Examination of Neurobehavioral Mechanisms in Tic Suppression

抽动抑制中神经行为机制的综合检查

• 批准号: 9297368
• 负责人: Christine A Conelea
• 金额: $ 15.48万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9297368
• 关键词: Address; Affect; Area; Attention deficit hyperactivity disorder; Award; Awareness; Behavior Therapy; Behavioral; Behavioral Mechanisms; Behavioral Model; Behavioral Paradigm; Behavioral tic; Biological Factors; Biological Models; Biology; Brain; Categories; Child; Chronic; Complex; Corpus striatum structure; Cues; Data; Diagnostic; Disease; Disease model; Ensure; Environment; Ethics; Frequencies; Functional disorder; Future; Gilles de la Tourette syndrome; Goals; Hyperactive behavior; Impairment; Intervention; Involuntary Movements; K-Series Research Career Programs; Knowledge; Lead; Link; Magnetic Resonance Imaging; Mental disorders; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methodology; Methods; Motor; Motor Cortex; Motor output; Movement; Movement Disorders; National Institute of Mental Health; Neuroanatomy; Neurobiology; Neurology; Neurosciences Research; Obsessive compulsive behavior; Pharmaceutical Preparations; Play; Problem behavior; Procedures; Process; Psychiatry; Psychological reinforcement; Psychology; Psychopathology; Punishment; Research; Research Personnel; Role; Sampling; Scientist; Stimulus; Stream; Structure; Technical Expertise; Time; Training; Transcranial magnetic stimulation; Work; Youth; behavioral study; career; contextual factors; design; effective therapy; experience; falls; functional disability; improved; innovation; neurobehavioral; neurobiological mechanism; neuropsychiatric symptom; psychosocial; public health relevance; repetitive behavior; repetitive transcranial magnetic stimulation; response; skills; somatosensory; therapy development; vocalization

DESCRIPTION (provided by applicant): This K23 Career Development Award is designed provide the training needed for the PI to achieve her long-term career goal of conducting independent, programmatic research on the neurobehavioral mechanisms underlying tics and repetitive behavior problems associated with cortico-striatal-thalamo-cortical (CSTC) circuit dysfunction. Consistent with this goal, the proposed study will focus on the neurobehavioral mechanisms underlying tic suppression in a sample of youth with chronic tics. This award builds on the PI's emerging expertise in tic and obsessive-compulsive spectrum disorders and experimental psychopathology methods to study behavioral mechanisms that impact tic expression. This award will extend the PI's research to include integrated study of behavioral and neurobiological mechanisms in tic suppression. Additional mentored training will ensure that the PI acquires the technical skills and advanced theoretical and scientific knowledge needed to develop, lead, and contribute to integrative, interdisciplinary disease mechanism research in mental disorders associated with CSTC circuit dysfunction. The highly structured training plan will enable the PI to obtain skills and knowledge in the following areas: 1) CSTC neurocircuitry and neuroanatomy, 2) transcranial magnetic stimulation (TMS) methodology, 3) use of magnetic resonance imaging (MRI) data to guide TMS navigation, 4) ethical and safe use of TMS in child psychopathology research, and 5) collaborative obsessive- spectrum neuroscience research. Training and research will be guided by an expert mentorship team comprised of leading scientists in the fields of psychiatry, psychology, and neurology. The research plan of this K23 award will examine the relationship between supplementary motor area (SMA) activation and tic suppression using an innovative methodology that combines 1 hz repetitive TMS (rTMS) vs. sham rTMS with an established behavioral tic suppression paradigm. Chronic tics are a disabling neuropsychiatric symptom and the most common movement disorder in children. The mechanisms underlying tic suppression are poorly understood but thought to involve an interaction between biological and contextual factors. SMA is a cortical node of the CSTC circuit that plays a key role in facilitating context-dependent motor output and is hyperactive in those with tics. The current study will probe the role of SMA activity in tic suppression using TMS, a non-invasive procedure that allows for the temporary modulation of cortical regions. Aim 1 will address whether inhibition of SMA excitability leads to changes in baseline tic frequencies, voluntary tic suppression, and tic suppressability in the presence of suppression-contingent reinforcement. Aim 2 will explore whether premonitory urge intensity changes in conjunction with inhibition of SMA excitability. This will be the first study to directly examine the relationsip between SMA functioning, tic suppression, and premonitory urge intensity. Results will refine our understanding of brain-context relationships involved in tic suppression and may have implications for the broader understanding of neurobehavioral processes involved in the suppression of other unwanted repetitive behaviors.

描述（由申请人提供）：该K23职业发展奖设计为PI提供了她实现她长期职业目标所需的培训，以实现有关处理混蛋的神经行为机制独立的，程序化研究以及与皮质 - 纹状体 - 毛刺 - 毛细血管 - 毛细血管 - 皮层（CSTC）电路相关的重复性行为问题的培训。与这一目标一致，拟议的研究将重点放在慢性测试青年样本中的TIC抑制作用的神经行为机制上。该奖项基于PI在TIC和强迫性谱系障碍和实验心理病理学方法方面的新兴专业知识，以研究影响TIC表达的行为机制。该奖项将扩大PI的研究，以在TIC抑制中包括对行为和神经生物学机制的综合研究。额外的指导培训将确保PI获得发展，领导和促进与CSTC电路功能障碍相关的综合性，跨学科疾病机制研究所需的技术技能以及先进的理论和科学知识。高度结构化的培训计划将使PI能够在以下领域获得技能和知识：1）CSTC神经记录和神经解剖学，2）经颅磁刺激（TMS）方法论，3）使用磁共振成像（MRI）数据以指导TMS导航，4）在儿童精神疗法研究中使用TMS导航，并在5）中进行探讨。培训和研究将由由精神病学，心理学和神经病学领域的主要科学家组成的专家指导团队指导。 该K23奖的研究计划将使用创新的方法论补充运动区域（SMA）激活和TIC抑制之间的关系，该方法将1 Hz重复的TMS（RTMS）与Sham RTMS与已建立的行为TIC抑制范式相结合。慢性抽搐是一种致命的神经精神症状，是儿童最常见的运动障碍。抑制作用抑制的机制知之甚少，但认为涉及生物学和情境因素之间的相互作用。 SMA是CSTC电路的皮质节点，在促进上下文依赖性电动机输出中起关键作用，并且在患有TIC的人中是多动的。当前的研究将使用TMS探测SMA活性在TIC抑制中的作用，TMS是一种非侵入性程序，允许对皮质区域进行临时调节。 AIM 1将解决对SMA兴奋性的抑制是否会导致基线TIC频率的变化，自愿抑制和在存在抑制加固的情况下抑制性。 AIM 2将探索预先敦促强度是否与抑制SMA兴奋性结合使用。这将是第一个直接检查SMA功能，抽动抑制和预先敦促强度之间关系的研究。结果将完善我们对抑制作用涉及的脑部秘密关系的理解，并可能对抑制其他不需要的重复行为涉及的神经行为过程的更广泛理解产生影响。

项目成果

Response Inhibition in Youth Undergoing Intensive Treatment for Obsessive Compulsive Disorder.

• DOI: 10.1016/j.jocrd.2022.100764
• 发表时间: 2022-11
• 期刊: Journal of obsessive-compulsive and related disorders
• 影响因子: 1.8
• 作者: Christine A. Conelea;Sarah Morris;N. McLaughlin;Erin Mamaril;K. Benito;B. Case;Abbe Garcia

Sensory Phenomena in Tourette Syndrome: Their Role in Symptom Formation and Treatment.

• DOI: 10.1007/s40474-014-0026-2
• 发表时间: 2014-12
• 期刊: Current developmental disorders reports
• 影响因子: 2

Response to Letter to the Editor regarding "Transcranial magnetic stimulation for treatment-resistant depression: Naturalistic outcomes for younger versus older patients".

回复关于“经颅磁刺激治疗难治性抑郁症：年轻患者与老年患者的自然结果”的致编辑信。

• DOI: 10.1016/j.jad.2017.08.033
• 发表时间: 2018
• 期刊: Journal of affective disorders
• 影响因子: 6.6
• 作者: Conelea,ChristineA;Philip,NoahS;Yip,AugustinG;Barnes,JenniferL;Niedzwiecki,MatthewJ;Greenberg,BenjaminD;Tyrka,AudreyR;Carpenter,LindaL
• 通讯作者: Carpenter,LindaL