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 (<45 and >50 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.

Figure 1.

Performance (hits-false alarms) in the previously published and current young subjects groups. The HERA model organization based on left DLPFC functional prevalence in encoding and right in retrieval is fully confirmed. The number of recognition errors in retrieval in the two reference blocks (i.e., baseline and sham) is also similar.

Figure 2.

Hemispheric interaction of rTMS effects and age groups during retrieval, according to the HERA model. Top, Young subjects show a clear hemispheric interaction (lower performance during right rTMS in retrieval and when rTMS had been left in encoding). Bottom, In older subjects, the level of performance during active rTMS blocks is generally lower, but the encoding asymmetry is preserved, whereas the retrieval asymmetry is no longer evident. Therefore, the HERA pattern is lost. Note that in old subjects, rTMS of the left DLPFC in retrieval disrupts performance more than rTMS delivered on the right. Statistics are described in Results. Hem., Hemisphere.

Figure 3.

Regressions between the subjects' age and hemispheric right-left asymmetries during encoding (HEA) and retrieval (HRA). a, During the encoding phase, no effect of age was found on hemispheric asymmetries. Indeed, the regression line was constantly above the (thick) zero line, indicating no asymmetry variation across the life span. b, During the retrieval phase, in contrast, the age strongly influenced the level of interhemispheric asymmetry, which begins to vanish approximately at 40 years of age. In both panels, some subjects with an opposite pattern of asymmetries can be appreciated (i.e., young without HERA and over 50 with HERA). Statistics are described in Results.