Cortical Inhibition and Mobility in Older Adults

老年人的皮质抑制和活动性

基本信息

批准号：
10251928
负责人：
Kathleen Elizabeth Hupfeld
金额：
$ 4.15万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-02 至 2021-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10251928
关键词：
Acute Address Adult Aerobic Exercise Affect Age Aging Alzheimer&apos s disease risk American Anterior Biomechanics Brain Brain imaging Cognitive Complex Dementia Development Elderly Equilibrium Exercise Exercise Test Functional disorder Future Gait Glutamates Glutamine Goals Health Hospitalization Impaired cognition Impairment Individual Differences International Intervention Knowledge Lead Link Lower Extremity Magnetic Resonance Spectroscopy Measures Mediating Mentorship Methods Motor Movement Muscle Muscle Contraction Neurobehavioral Manifestations Neurosciences Neurotransmitters Outcome Performance Posture Process Quality of life Reporting Research Research Personnel Research Project Grants Skeletal Muscle Specificity System Testing Training Transcranial magnetic stimulation Upper Extremity Walking Work age difference age effect age related cognitive testing dementia risk disability exercise intervention fall risk falls functional disability gamma-Aminobutyric Acid health goals healthy aging high risk improved mild cognitive impairment mortality motor control motor impairment motor symptom novel preservation prevent programs response restoration therapy development young adult

项目摘要

Nearly 25% of Americans age 65+ report serious mobility problems. Mobility impairments decrease quality of life and predict increased risk of falls, disability, and mortality. However, the contribution of age-related brain changes to mobility impairments is not well understood. F99 work will examine how cortical inhibitory function relates to gait and balance declines with aging. K00 work will examine the same questions in mild cognitive impairment (MCI) and test exercise as an intervention to improve cortical inhibitory function. The sponsor's (Dr. Rachael Seidler) past work supports the novel hypothesis that declines in cortical inhibitory processes at least partially underlie motor impairments with aging. For Aim 1 (F99), the candidate is collecting two measures of lower limb cortical inhibition in 30 young and 30 older adults: 1) gamma-aminobutyric acid (GABA)-edited magnetic resonance spectroscopy (MRS) and 2) transcranial magnetic stimulation-induced cortical silent period. GABA-edited MRS provides a measure of GABA neurotransmitter concentration, while cortical silent periods provide a measure of functional cortical inhibition during muscle activity. The F99 work addresses whether these two measures of cortical inhibition are reduced in older age (Aim 1a) and whether cortical inhibition relates to individual differences in gait (Aim 1b) and balance (Aim 1c). Mobility is often more impaired in MCI than in healthy aging. Motor symptoms typically arise much earlier than cognitive symptoms, and presence of motor symptoms relates to higher risk of Alzheimer's disease. Past work suggests that cortical inhibitory function is impaired in MCI and dementia, supporting that changes in cortical inhibition could be a component of MCI. Thus, for Aim 2 (K00), the candidate will work with Dr. Kirk Erickson to test whether cortical inhibition is reduced in MCI compared to healthy aging (Aim 2a) and if cortical inhibition relates to gait and balance in MCI (Aim 2b). Given relationships between cortical inhibition and motor control in healthy adults, it is feasible that cortical inhibition changes could also relate to mobility declines in MCI. Understanding neurotransmitter systems involved in mobility declines is important for development of interventions. Thus, the candidate will test whether aerobic exercise influences cortical inhibition in aging and MCI (Aim 2c). Past work demonstrated effects of exercise on cortical inhibition in young adults, but this has yet to be tested in aging or MCI. This work directly contributes to the NIA's major goals of preserving mobility in aging and studying brain changes with MCI. To successfully complete these aims, the candidate will receive extensive training from an expert mentorship team in biomechanics, brain imaging, brain stimulation, MCI, and exercise intervention work. This training will provide the candidate with a comprehensive toolkit to succeed as an aging researcher, with my future independent research program focused on: 1) determining the brain changes that contribute to motor declines in older age and MCI, and 2) identifying interventions to preserve motor function in older age and MCI.

近25％的65岁以上的美国人报告了严重的流动问题。流动性障碍会降低生活质量，并预测跌倒，残疾和死亡率的风险增加。但是，与年龄相关的大脑变化对移动性障碍的贡献尚不清楚。 F99的工作将研究皮质抑制功能与步态的关系以及与衰老的平衡下降。 K00工作将在轻度认知障碍（MCI）和测试运动中研究相同的问题，以改善皮质抑制功能。赞助商的（Rachael Seidler博士）过去的工作支持了新的假设，该假设在皮质抑制过程中的下降至少部分构成了随着衰老的运动障碍的基础。对于AIM 1（F99），候选人正在收集30名年轻和30名老年人的下肢皮质抑制作用的两种指标：1）γ-氨基丁酸（GABA）编辑的磁共振光谱（MRS）和2）经颅磁刺激诱导的皮层静态时期。 GABA编辑的MRS提供了GABA神经递质浓度的量度，而皮质无声时期则提供了肌肉活性期间功能性皮质抑制的量度。 F99的工作解决了这两种皮质抑制措施是否减少了老年（AIM 1A），以及皮质抑制是否与步态的个体差异（AIM 1B）和平衡（AIM 1C）有关。在MCI中，移动性通常比健康衰老更受损害。运动症状通常比认知症状早得多，运动症状的存在与阿尔茨海默氏病的较高风险有关。过去的工作表明，MCI和痴呆症中皮质抑制功能受损，支持皮质抑制作用的变化可能是MCI的组成部分。因此，对于AIM 2（K00），候选人将与Kirk Erickson博士一起测试MCI的皮质抑制是否减少了与健康的衰老相比（AIM 2A），以及皮质抑制与MCI的步态和平衡有关（AIM 2B）。鉴于健康成年人皮质抑制与运动控制之间的关系，可行的是，皮质抑制变化也可能与MCI的迁移率下降有关。了解涉及流动性下降的神经递质系统对于开发干预措施很重要。因此，候选人将测试有氧运动是否影响衰老和MCI的皮质抑制（AIM 2C）。过去的工作表明运动对年轻人皮质抑制的影响，但这尚未在衰老或MCI中进行测试。这项工作直接促进了NIA在通过MCI进行衰老和研究大脑变化方面流动性的主要目标。为了成功完成这些目标，候选人将获得有关生物力学，脑成像，大脑刺激，MCI和运动干预工作的专家指导团队的广泛培训。这项培训将为候选人提供一个全面的工具包，以成功成为老龄化研究人员，而我的未来独立研究计划的重点是：1）确定大脑变化会导致大脑变化，导致年龄较大的人和MCI的运动降低，以及2）确定在老年和MCI中保留运动功能的干预措施。

项目成果

期刊论文数量（16）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Age differences in adaptation of medial-lateral gait parameters during split-belt treadmill walking.

DOI：
10.1038/s41598-021-00515-z
发表时间：
2021-10-27
期刊：
Scientific reports
影响因子：
4.6
作者：
Fettrow T;Hupfeld K;Reimann H;Choi J;Hass C;Seidler R
通讯作者：
Seidler R

TMS-induced silent periods: A review of methods and call for consistency.

DOI：
10.1016/j.jneumeth.2020.108950
发表时间：
2020-12-01
期刊：
Journal of neuroscience methods
影响因子：
3
作者：
Hupfeld KE;Swanson CW;Fling BW;Seidler RD
通讯作者：
Seidler RD

Sensory system-specific associations between brain structure and balance.

DOI：
10.1016/j.neurobiolaging.2022.07.013
发表时间：
2022-11
期刊：
NEUROBIOLOGY OF AGING
影响因子：
4.2
作者：
Hupfeld, K. E.;McGregor, H. R.;Hass, C. J.;Pasternak, O.;Seidler, R. D.
通讯作者：
Seidler, R. D.

Neural correlates of gait adaptation in younger and older adults.

DOI：
10.1038/s41598-023-30766-x
发表时间：
2023-03-08
期刊：
SCIENTIFIC REPORTS
影响因子：
4.6
作者：
Fettrow, Tyler;Hupfeld, Kathleen;Hass, Chris;Pasternak, Ofer;Seidler, Rachael
通讯作者：
Seidler, Rachael

Impacts of spaceflight experience on human brain structure.

DOI：
10.1038/s41598-023-33331-8
发表时间：
2023-06-08
期刊：
SCIENTIFIC REPORTS
影响因子：
4.6
作者：
McGregor, Heather R.;Hupfeld, Kathleen E.;Pasternak, Ofer;Beltran, Nichole E.;De Dios, Yiri E.;Bloomberg, Jacob J.;Wood, Scott J.;Mulavara, Ajitkumar P.;Riascos, Roy F.;Reuter-Lorenz, Patricia A.;Seidler, Rachael D.
通讯作者：
Seidler, Rachael D.