Research 1-Hogeveen

研究1-霍格文

• 批准号: 10026517
• 负责人: Jeremy P Hogeveen
• 金额: $ 25.43万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10026517
• 关键词: Affect; Amygdaloid structure; Anterior; Apple; Automobile Driving; Behavior; Behavioral; Biological Assay; Brain; Brain Diseases; Chronic; Clinical; Cognitive; Cognitive Therapy; Consult; Corpus striatum structure; Data; Decision Making; Deep Brain Stimulation; Development; Dorsal; Effectiveness; Environment; Event; Functional Magnetic Resonance Imaging; Funding; Future; Goals; Health Benefit; Human; Impairment; Insula of Reil; Intervention; Laboratories; Lead; Learning; Mentors; Methods; Motivation; National Institute of Mental Health; Neurologic; Neurology; Neurosciences; New Mexico; Outcome; Participant; Pathologic; Pathology; Patients; Penetrating Brain Injury; Pharmacotherapy; Prefrontal Cortex; Psychiatric therapeutic procedure; Records; Recovery; Rehabilitation therapy; Research; Research Personnel; Resources; Rewards; Risk; Scientist; Site; Social support; Specificity; Stimulus; Symptoms; System; TBI Patients; Task Performances; Transcranial magnetic stimulation; Traumatic Brain Injury; Traumatic injury; United States National Institutes of Health; Universities; Ventral Striatum; Work; arm; base; cingulate cortex; clinically significant; cognitive ability; cognitive function; common symptom; disabling symptom; effective therapy; experience; experimental study; functional MRI scan; high reward; image guided; innovation; insight; motivated behavior; nervous system disorder; neural circuit; neuroregulation; novel; personalized approach; personalized medicine; precision medicine; programs; recruit; relating to nervous system; repaired; repetitive transcranial magnetic stimulation; side effect; willingness

PROJECT SUMMARY The overarching goals of the current CoBRE mentored PI project are to better understand, and precisely modulate, the neurocomputational mechanisms underlying apathy in patients with chronic moderate-to-severe traumatic brain injury (msTBI). Previous studies have established that apathy–characterized by a loss of motivation–is a common and debilitating symptom of msTBI, but the underlying neural pathologies causing apathy in msTBI remain unknown. Clinically, existing treatments for apathy in msTBI have limited efficacy, either due to their reliance on high-level cognitive abilities that are often impaired in msTBI (e.g. cognitive behavioral therapy), or their potential to induce unwanted and deleterious side effects due to a lack of circuit- specificity (e.g. pharmacotherapies that modulate dopaminergic tone throughout the brain). Therefore, there are significant needs for i) rigorous experimental neuroscience studies on the specific motivated behavior circuits that–when damaged–cause apathy in msTBI, and ii) the development of circuit-specific approaches for modulating motivation circuits in apathetic patients, not reliant on high-level cognitive functioning. In this project, the PI will use task-based functional magnetic resonance imaging (fMRI) to determine whether apathy in msTBI is associated with damage to the functional neural circuits involved in computing the anticipated reward value of stimuli in the environment (i.e., stimulus valuation), and/or damage to the circuits involved in determining whether a given reward is worth the effort required to obtain it (i.e., willingness-to-engage effort). Additionally, the PI will leverage the insights derived from this msTBI project to determine whether task fMRI- guided repetitive transcranial magnetic stimulation (rTMS) is a viable approach for circuit-specific modulation of value and effort circuits. By establishing the effectiveness of fMRI-guided rTMS for selectively engaging value and effort computation circuits, this project will form the bedrock for future R01 projects refining personalized rTMS approaches for treating neurological and psychiatric patients experiencing a loss of motivation. The PI’s goal is to build a world-class human neuroscience laboratory that develops innovative methods for characterizing and stimulating the neural circuits underlying aberrant motivated behavior through independent R01 funding. The current mentored PI project provides an ideal opportunity for the PI to jump-start this research program. The senior mentors Drs. Mayer and Pirio Richardson have proven track records with NIH funding and extensive experience using fMRI to elucidate the functional deficits caused by TBI (Dr. Mayer) and using rTMS as a treatment for neurological patients (Dr. Pirio Richardson). Additionally, two leading scientists (Drs. Husain, Claus, and Costa) who conduct state-of-the-art research on the neurocomputational bases of motivated behavior and its pathologies have committed to consult on the proposed project. Therefore, the mentoring team will be well-suited to guide the PI as he leads this project, and will facilitate his transition to becoming an independent R01-funded investigator.

项目总结