FMRI and TMS Analysis of Frontal Lobes in Aging

描述(申请人提供)：本提案的目的是应用经颅磁刺激(TMS)和功能磁共振成像(FMRI)来完善老年人健康额叶功能的模型。额叶功能随年龄增长而变化。对执行记忆任务的年轻人和老年人的fMRI激活研究表明，老年人在年轻人表现出单侧激活的情况下表现出双侧额叶激活。表现出双侧激活的老年人表现出更好的记忆力。目前还没有确定这些额外的区域是否参与了所执行的任务。TMS将被应用于干扰老年人更强烈地招募的局部区域，以确定这些区域是否对记忆处理是必要的。第一项研究采用了言语工作记忆范式，在功能磁共振成像中，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TMS研究表明，在年轻人中，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脑招募时间模式，这可能有助于fMRI激活的差异。第二项和第三项研究延伸到老年人，这是一项对年轻人进行的情景记忆的TMS研究。功能成像研究表明，左额叶在编码时比检索时更活跃，右额叶在检索时比编码时更活跃。先前的TMS研究表明，在年轻人中，TMS在左侧额叶和右侧额叶的干扰程度符合基于功能激活相对差异的预测。由于老年人通常表现出较少的偏侧化功能激活，我们假设TMS刺激将同等地破坏两个半球的表现。额叶fMRI激活不对称程度的个体差异将与右侧TMS与左侧TMS的表现中断程度相关。

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.