Cortico-subcortical neuronal circuitry associated with reconsolidation of human procedural memories

Abstract

The ability of the mammalian brain to modify existing memories through reconsolidation may be crucial for skill acquisition. The neural mechanisms of memory modification have been commonly studied at the cellular level. Yet surprisingly, the human brain systems-level mechanisms involved in day-to-day modification of existing procedural memories remain largely unknown. Here, we studied differences in functional magnetic resonance imaging (fMRI) regional signal activity and inter-regional functional connectivity in subjects in whom motor memory modification was interfered with by repetitive transcranial magnetic stimulation (rTMS), relative to subjects with intact memory modification. As a consequence, subjects with impaired memory modification had lower activity in the supplementary motor area (SMA) and weaker functional connectivity between M1, SMA, anterior cerebellum consistently engaged in early learning, and sensorimotor striatum active in later learning stages. These findings, identifying a link between engagement of this network and successful memory modification, suggest that memory reconsolidation may represent a transitional bridge between early and late procedural learning, underlying efficient skill acquisition.

Keywords: Learning; Memory; Motor-fMRI; TMS.

Figure 1

Experimental design. All participants performed a sequential finger-tapping task, in which they were trained to repeatedly perform with their nondominant left hand a constant sequence of five finger movements, with performance measured as the number of correct sequences during each fixed 10 s trial (Karni et al., 1995; Korman et al., 2007; Censor et al., 2010). Following initial memory formation and test subjects were divided into 2 groups. To interfere with memory modification, one group was stimulated with 1-Hz rTMS applied to the primary motor cortex (M1) during memory reactivation trials. The second group received control rTMS to a vertex position applied simultaneously with peripheral nerve stimulation (ulnar nerve at the wrist) to mimic disruption of manual performance present when stimulating M1 without reducing memory modification (see Fig. 2). Memory modification and fMRI measurements were assessed on a retest the following day.

Figure 2

Reducing memory modification. A, Test and Retest scores for the rTMS interference and control stimulation groups. B, Applying rTMS interference during reactivation of the existing memory reduced memory modification relative to the control stimulation group which exhibited intact, standard memory modification (Walker et al., 2003; Censor et al., 2010). Error bars depict standard errors of the mean.

Figure 3

Difference in BOLD signal activity following reduced and intact memory modification. A, Whole brain analysis identified reduced BOLD contrast of tapping vs. rest at retest specifically in the SMA proper extending to the caudal cingulate in the reduced memory modification relative to the intact modification group. Results are corrected for multiple comparisons at the cluster level (P<0.05). B, BOLD contrast activation in the SMA cluster when memory modification was reduced compared to the intact memory modification group. Error bars depict standard errors of the mean.

Figure 4

Functional connectivity with M1 following reduced and intact memory modification. Brain areas showing weaker connectivity with the primary cortical region (M1) at retest after reduced (A) and intact (B) memory modification.