FMRI and TMS Analysis of Frontal Lobes in Aging

描述（由申请人提供）：本提案的目的是应用经颅磁刺激（TMS）和功能MRI （fMRI）来完善老年人健康额叶功能模型。额叶功能随着年龄的增长而变化。FMRI对年轻人和老年人执行记忆任务的激活研究表明，在年轻人表现单侧激活的情况下，老年人表现出双侧额叶激活。双侧激活更强烈的老年人表现出更好的记忆力。目前还不清楚这些额外的区域是否参与了所执行的任务。经颅磁刺激将被应用于干扰老年人更强烈招募的局部区域，以确定这些区域对记忆处理是否必要。第一项研究应用了口头工作记忆范式，该范式在功能磁共振成像中显示，年轻人主要是左额叶激活，老年人主要是双侧激活。先前的一项经颅磁刺激研究表明，年轻人短暂的右额叶受累先于左额叶受累。如果老年人表现出不同的右半球招募的时间模式，这可能会导致fMRI激活的差异。第二个和第三个研究扩展到老年人，在年轻人中进行的情景记忆的TMS研究。功能成像研究表明，左侧额叶在编码过程中比检索过程更活跃，右侧额叶在检索过程中比编码过程更活跃。先前的经颅磁刺激研究表明，在年轻人中，经颅磁刺激对年轻人左额叶和右额叶的破坏程度遵循基于功能激活的相对差异的预测。由于老年人一般表现出较少的侧化功能激活，我们假设经颅磁刺激会对两个半球的表现造成同样的破坏。额叶fMRI激活不对称程度的个体差异将与右侧与左侧经颅磁刺激的表现中断程度有关。

DESCRIPTION (provided by applicant): The aim of this proposal is to apply transcranial magnetic stimulation (TMS) and functional MRI (fMRI) to refine models of healthy frontal lobe functioning in older adults. Frontal lobe functioning changes with increasing age. FMRI activation studies of young and older adults performing memory tasks demonstrate that older adults exhibit bilateral frontal lobe activation under conditions where young adults display unilateral activation. Older adults demonstrating bilateral activation more strongly demonstrate better memory. It has not been established whether these additional regions are involved in the task performed. TMS will be applied to disrupt focally regions more intensely recruited by older adults to determine whether those areas are necessary for memory processing. The first study applies a verbal working memory paradigm which in fMRI has demonstrated predominantly left frontal activation in young adults and bilateral activation in older adults. A previous TMS study suggested that transient right frontal involvement precedes left frontal involvement in young adults. If older adults demonstrate a different temporal pattern of right hemisphere recruitment, this could contribute to fMRI activation differences. The second and third studies extend to older adults a TMS study of episodic memory performed in young adults. Functional imaging research suggests that the left frontal lobe is more active during encoding than retrieval and the right frontal lobe is more active during retrieval than encoding. The previous TMS study demonstrated that in young adults, degree of disruption with TMS in the left versus right frontal lobes of young adults followed the predictions based on relative differences in functional activation. Because older adults demonstrate less lateralized functional activation in general, we hypothesize that TMS stimulation will disrupt performance equally in both hemispheres. Individual differences in the degree of asymmetry in frontal lobe fMRI activation will be associated with degree of performance disruption with right versus left TMS.