Central thalamic deep brain stimulation to regulate arousal and cognition

中枢丘脑深部脑刺激调节觉醒和认知

• 批准号: 10372092
• 负责人: JONATHAN L BAKER
• 金额: $ 61万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10372092
• 关键词: 3-Dimensional; Anatomic Models; Anatomy; Animal Model; Animals; Anodes; Anterior; Arousal; Attention; Axon; BRAIN initiative; Behavior; Behavioral; Biological Markers; Brain; Brain Diseases; Brain Injuries; Brain Stem; Brain imaging; Cathodes; Chronic; Clinical; Clinical Research; Cognition; Cognitive; Communication; Data; Deep Brain Stimulation; Device Designs; Devices; Dorsal; Electric Stimulation; Electrophysiology (science); Faculty; Family; Fatigue; Feasibility Studies; Fiber; Functional disorder; Future; Geometry; Goals; Human; Impaired cognition; Implant; Impulsivity; Individual; Injury; Investigational Therapies; Knowledge; Lead; Link; Macaca; Measures; Medial; Methods; Microelectrodes; Mission; Modeling; Monkeys; Motivation; Movement Disorders; Myelin; National Institute of Neurological Disorders and Stroke; Nerve Degeneration; Neurocognitive; Neurologic; Neurology; Neurons; Neurosciences; Nuclear; Optical Coherence Tomography; Outcome; Pathway interactions; Patients; Performance; Pharmaceutical Preparations; Physiological; Physiology; Play; Positioning Attribute; Primates; Prosencephalon; Public Health; Regulation; Research; Resolution; Resources; Role; Safety; Shapes; Short-Term Memory; Signal Transduction; Site; Societies; Stains; System; Testing; Thalamic structure; Traumatic Brain Injury; Treatment Efficacy; Work; base; biomedical imaging; biophysical model; cognitive capacity; cognitive performance; cognitive task; design; disability; effective therapy; electric field; experimental study; flexibility; improved; in vivo; innovation; neuropsychiatric disorder; neuropsychiatry; neuroregulation; nonhuman primate; novel; optical imaging; pre-clinical; preclinical study; predictive modeling; prospective test; recruit; sustained attention; tractography; vigilance

Deep brain stimulation (DBS) is an established therapy for various movement disorders and is now being investigated to treat a widening range of neurological and neuropsychiatric conditions. However, to fully realize the promise of DBS as a therapy, we need to better understand how it modulates neuronal activity within both the local DBS target and in the brain as a whole. The focus of this proposal is to advance a novel method of field-shaping central thalamic-DBS (fsCT-DBS) to modulate arousal and cognition. Arousal regulation is profoundly impacted in patients with structural brain injuries and is a common and untreated sequelae of many patients suffering from neurodegenerative and neuropsychiatric illnesses. In prior work we discovered a novel method of CT-DBS, where anodes and cathodes are separated across multiple implanted DBS leads within a specific region of the central thalamus, here termed `field-shaping CT-DBS' (fsCT-DBS). Here we will prospectively test and characterize behavioral performance of animals during fsCT-DBS. The central hypothesis to be tested here is that robust regulation of arousal with fsCT-DBS arises through selective delivery of electric stimulation to a specific fiber tract within the central thalamus, the medial aspect of the dorsal thalamic tegmental tract (DTTm). This fiber tract consists of axons originating from central thalamic nuclear groups and brainstem arousal centers that project to the anterior forebrain and are believed to play a crucial role in supporting cognition through the regulation of activity levels and brain-wide communication. The aims of this proposal seek to establish an anatomically accurate predictive biophysical model of the DTTm and to systematically test new modes of fsCT-DBS to enhance the use and capacity of cognitive resources in healthy behaving macaque monkeys. First, state-of-the-art biomedical imaging will be combined with ultrahigh- resolution optical imaging to construct predictive biophysical models of the DTTm. Second, the effects of fsCT- DBS on DTTm recruitment will be measured by comparing performance on a sustained attention/vigilance task and in two paradigms requiring additional cognitive resources, a set-shifting categorization task and a working memory task. The latter two tasks require cognitive flexibility, a faculty that is degraded in the majority of patients with neuropsychiatric disorders and structural brain injuries. Third, the use of adaptive fsCT-DBS will be explored using a new clinical-grade closed-loop DBS device. The identification and predictive biophysical modeling of the local fsCT-DBS target, the DTTm, the use of multipolar field shaping to validate the model predictions through behavior and large-scale physiology, and exploration of close-loop DBS are all highly innovative aspects of this proposal as they will improve our understanding of how to precisely target fsCT-DBS to robustly and reliability regulate anterior forebrain activity and support cognition. The use of healthy non- human primates as a model to validate the proposed approach is essential to guiding and facilitating design specifications for a new clinical-grade fsCT-DBS system for use in humans.

脑深部电刺激（DBS）是一种治疗各种运动障碍的有效方法