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 职业发展奖旨在为 PI 提供所需的培训，以实现她的长期职业目标，即对抽动和与皮质-纹状体-丘脑-皮质 (CSTC) 回路功能障碍相关的重复行为问题的神经行为机制进行独立的程序性研究。与这一目标一致，拟议的研究将重点关注患有慢性抽动症的青少年样本中抽动抑制背后的神经行为机制。该奖项建立在 PI 在抽动和强迫谱系障碍方面的新兴专业知识以及研究影响抽动表达的行为机制的实验精神病理学方法的基础上。该奖项将扩大 PI 的研究范围，包括抽动抑制中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 获得开发、领导和促进与 CSTC 回路功能障碍相关的精神障碍的综合、跨学科疾病机制研究所需的技术技能和先进的理论和科学知识。高度结构化的培训计划将使 PI 能够获得以下领域的技能和知识：1) CSTC 神经回路和神经解剖学，2) 经颅磁刺激 (TMS) 方法，3) 使用磁共振成像 (MRI) 数据指导 TMS 导航，4) 在儿童精神病理学研究中道德和安全地使用 TMS，以及 5) 协作强迫谱神经科学研究。培训和研究将由由精神病学、心理学和神经病学领域的顶尖科学家组成的专家指导团队指导。 该 K23 奖项的研究计划将使用一种创新方法来研究辅助运动区 (SMA) 激活和抽动抑制之间的关系，该方法将 1 hz 重复 TMS (rTMS) 与假 rTMS 与已建立的行为抽动抑制范例相结合。慢性抽动是一种致残性神经精神症状，也是儿童最常见的运动障碍。人们对抽动抑制的机制知之甚少，但认为涉及生物因素和背景因素之间的相互作用。 SMA 是 CSTC 回路的一个皮质节点，在促进上下文相关的运动输出方面发挥着关键作用，并且在抽动患者中过度活跃。目前的研究将探讨 SMA 活动在使用 TMS 抑制抽动中的作用，TMS 是一种非侵入性程序，可以暂时调节皮质区域。目标 1 将解决 SMA 兴奋性的抑制是否会导致基线抽动频率、自愿抽动抑制以及存在抑制相关强化的情况下抽动抑制性的变化。目标 2 将探讨预兆冲动强度的变化是否与 SMA 兴奋性的抑制相关。这将是第一项直接研究 SMA 功能、抽动抑制和预兆冲动强度之间关系的研究。结果将完善我们对抽动抑制中涉及的大脑环境关系的理解，并可能对更广泛地理解抑制其他不需要的重复行为中涉及的神经行为过程产生影响。

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