Reversing Synchronized Brain Circuits with Targeted Auditory-Somatosensory Stimulation to Treat Phantom Percepts

通过有针对性的听觉体感刺激逆转同步大脑回路来治疗幻觉

• 批准号: 9390327
• 负责人: SUSAN E SHORE
• 金额: $ 241.1万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9390327
• 关键词: Acoustic Nerve; Acoustics; Affect; Aftercare; Animals; Apical; Auditory; Auditory system; Behavioral; Brain; Brain Stem; Cavia; Cell Nucleus; Cells; Cues; Data; Dendrites; Disease; Dose; Double-Blind Method; Electric Stimulation; Functional disorder; Fusiform Cell; Goals; Hearing; Human; Hyperactive behavior; Impairment; Interneurons; Lead; Length; Life; Long-Term Potentiation; Loudness; Measures; Mental Depression; Modeling; Monitor; Neurons; Noise; Outcome; Outcome Measure; Output; Parkinson Disease; Pathologic; Pathology; Perception; Physiological; Population; Process; Questionnaires; Research; Role; Stimulus; Synapses; Synaptic plasticity; System; Systems Integration; Testing; Tinnitus; Trigeminal System; United States; Withholding Treatment; arm; base; dorsal cochlear nucleus; dorsal column; dosage; experimental study; human study; human subject; insight; motor disorder; multisensory; neural circuit; novel; relating to nervous system; response; sensory system; somatosensory; sound; stimulus interval; successful intervention; treatment duration

Abstract The dorsal cochlear nucleus (DCN) integrates auditory and somatosensory information through circuitry that modulates activity of the principal output neurons of the circuit, the fusiform cells. Fusiform cells receive somatosensory information via synapses on their apical dendrites and acoustic information via their basal dendrites. When somatosensory activation is combined with sound, the circuit can be strengthened or weakened depending on the order of the bimodal stimuli. This process is called stimulus timing dependent plasticity. In the condition of phantom sound perception, or tinnitus, the DCN circuitry is strengthened to increase the firing rates and synchrony of fusiform cells. This proposal seeks to investigate the effects of manipulations on the circuitry of this first auditory brainstem nucleus by implementing a bimodal sound + electrical stimulus paradigm to alter the circuit in normal and pathological conditions. Animal and human studies will be conducted to optimize the stimulation parameters/dosages necessary to weaken the circuit and thus ameliorate the pathological condition. This will ultimately lead to treatments for neural disorders involving hyperactive or hyper synchronous circuits such as those identified for tinnitus or Parkinson's disease.

摘要 耳蜗背核（DCN）通过电路整合听觉和体感信息， 调节回路的主要输出神经元，梭形细胞的活动。梭形细胞接受 躯体感觉信息通过其顶端树突上的突触传递， 树突当躯体感觉激活与声音结合时，该回路可以被加强， 根据双峰刺激的顺序减弱。这个过程被称为刺激时间依赖性 可塑性在幻听或耳鸣的情况下，DCN电路被加强， 增加梭形细胞的放电频率和同步性。本建议旨在研究 通过实施双峰声音+ 电刺激范例来改变正常和病理条件下的电路。动物和人类 将进行研究以优化削弱电路所需的刺激参数/剂量， 从而改善病理状态。这将最终导致神经疾病的治疗， 过度活跃或超同步回路，如耳鸣或帕金森氏病。