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: 8876805
• 负责人: Christine A Conelea
• 金额: $ 2.07万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8876805
• 关键词: Address; Affect; Area; Attention deficit hyperactivity disorder; Award; Awareness; Behavior; 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; Health; Impairment; Intervention; 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; Research Training; Role; Sampling; Scientist; Stimulus; Stream; Structure; Symptoms; Time; Training; Transcranial magnetic stimulation; Work; Youth; base; career; contextual factors; design; effective therapy; experience; falls; functional disability; improved; innovation; neurobehavioral; neurobiological mechanism; neuropsychiatry; psychosocial; 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，即对与皮质-纹状体-丘脑-皮质（CSTC）回路功能障碍相关的抽搐和重复行为问题的神经行为机制进行独立的、程序化的研究。与这一目标一致，本研究将重点研究慢性抽动青年样本中抽动抑制的神经行为机制。该奖项建立在PI在抽动症和强迫症谱系障碍方面的新兴专业知识和实验精神病理学方法的基础上，以研究影响抽动症表达的行为机制。该奖项将扩大PI的研究，包括抽搐抑制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获得所需的技术技能和先进的理论和科学知识，以开展、领导和促进与CSTC电路功能障碍相关的精神障碍的综合、跨学科疾病机制研究。高度结构化的培训计划将使PI获得以下领域的技能和知识：1)CSTC神经电路和神经解剖学，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)合作强迫症谱系神经科学研究。培训和研究将由一个由精神病学、心理学和神经病学领域的顶尖科学家组成的专家指导小组指导。K23奖的研究计划将使用一种创新的方法，将1hz重复性经颅磁刺激（rTMS）与假性经颅磁刺激（sham rTMS）相结合，并结合已建立的行为抽搐抑制范式，研究辅助运动区（SMA）激活与抽搐抑制之间的关系。慢性抽搐是一种致残的神经精神症状，也是儿童中最常见的运动障碍。抽搐抑制的机制尚不清楚，但被认为涉及生物和环境因素之间的相互作用。SMA是CSTC回路的皮质节点，在促进情境依赖的运动输出中起关键作用，在抽搐患者中过度活跃。目前的研究将利用经颅磁刺激（一种允许暂时调节皮质区域的非侵入性程序）探索SMA活性在抽搐抑制中的作用。目的1将探讨SMA兴奋性的抑制是否会导致基线抽动频率、自主抽动抑制和在抑制-偶然强化存在下的抽动抑制性的变化。目的2将探讨先兆冲动强度的变化是否与SMA兴奋性的抑制有关。这将是第一个直接研究SMA功能、抽动抑制和先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脑-环境关系的理解，并可能对更广泛地理解涉及抑制其他不想要的重复行为的神经行为过程产生影响。