Age-Related Functional Changes of Prefrontal Cortex in Long-Term Memory: A Repetitive Transcranial Magnetic Stimulation Study

Abstract

Neuroimaging findings suggest that the lateralization of prefrontal cortex activation associated with episodic memory performance is reduced by aging. It is still a matter of debate whether this loss of asymmetry during encoding and retrieval reflects compensatory mechanisms or de-differentiation processes. We addressed this issue by the transient interference produced by repetitive transcranial magnetic stimulation (rTMS), which directly assesses causal relationships between performance and stimulated regions. We compared the effects of rTMS (a rapid-rate train occurring simultaneously to the presentation of memoranda) applied to the left or right dorsolateral prefrontal cortex (DLPFC) on visuospatial recognition memory in 66 healthy subjects divided in two classes of age (Ͻ45 and Ͼ50 years).In young subjects, rTMS of the right DLPFC interfered with retrieval more than left DLPFC stimulation. The asymmetry of the effect progressively vanished with aging, as indicated by bilateral interference effects on recognition performance. Conversely, the predominance of left DLPFC effect during encoding was not abolished in elders, thus probing its causal role for encoding along the life span. Findings confirm that the neural correlates of retrieval modify along aging, suggesting that the bilateral engagement of the DLPFC has a compensatory role on the elders' episodic memory performance.

The cognitive neuroscience of ageing

“…Interestingly, studies using transcranial magnetic stimulation (TMS) also have provided some support for the idea that increased bilateral PFC activation is beneficial for performance in older adults. Two studies have shown that using TMS to reduce activity in either the left PFC during encoding or the right PFC during retrieval reduces memory performance in younger adults, but has less effect in older adults, presumably because the unstimulated hemisphere can support the function when the other is inactivated 50,51 . Therefore, these studies all suggest that older adults can recruit higher levels of brain activity than young adults, often in the PFC, and that this additional activity can aid performance of the old adults who are best able to engage it.…”

Visual dominance and multisensory integration changes with age

“…Bilateral recruitment of parietal and prefrontal cortices was primarily observed in older participants who performed better or as well as young adults on a variety of perceptual and cognitive tasks (Cabeza et al, 2002;Grady et al, 1994;Park & Reuter-Lorenz, 2009;ReuterLorenz & Cappell, 2008;Thorpe et al, 1996). Furthermore, inhibition of prefrontal activity during recognition memory tasks significantly impaired older adults' performance (Rossi et al, 2004), whereas stimulation of prefrontal activity in under-performing older adults improved memory scores (Sole-Padulles et al, 2006) suggesting an adaptive role of prefrontal recruitment in healthy aging.…”

Bilateral recruitment of prefrontal cortex in working memory is associated with task demand but not with age

“…Actually, in the studies that have shown the HAROLD phenomenon (2)(3)(4)(5)11), all subjects worked on the same memory tasks despite the fact that cognitive performance of older adults deteriorates, and WM is one of the most affected cognitive functions (12)(13)(14). This cognitive deterioration might make a task subjectively more demanding for older subjects, so that they need the recruitment of contralateral counterparts in prefrontal cortex to perform as well as the young subjects (14)(15)(16).…”

“…To distinguish between these alternatives, we asked whether the activation strengths in cross-hemispheric pairs of prefrontal areas differ between hemispheres of both young and old adults when we match the subjective difficulty of WM tasks, and task demands are high. We specifically focused on dorsolateral prefrontal cortex (DLPFC) and anterior prefrontal cortex (aPFC) because these areas have been shown to be bilaterally engaged in elderly adults during memory tasks (2,11). We additionally considered ventrolateral prefrontal Significance One principle of human cerebral cortex is its lateralized functional architecture supporting processes such as language, precise motor control of the hands, and working memory.…”