Modification of existing human motor memories is enabled by primary cortical processing during memory reactivation

Abstract

One of the most challenging tasks of the brain is to constantly update the internal neural representations of existing memories. Animal studies have used invasive methods such as direct microfusion of protein inhibitors to designated brain areas, in order to study the neural mechanisms underlying modification of already existing memories after their reactivation during recall [1-4]. Because such interventions are not possible in humans, it is not known how these neural processes operate in the human brain. In a series of experiments we show here that when an existing human motor memory is reactivated during recall, modification of the memory is blocked by virtual lesion [5] of the related primary cortical human brain area. The virtual lesion was induced by noninvasive repetitive transcranial magnetic stimulation guided by a frameless stereotactic brain navigation system and each subject's brain image. The results demonstrate that primary cortical processing in the human brain interacting with pre-existing reactivated memory traces is critical for successful modification of the existing related memory. Modulation of reactivated memories by noninvasive cortical stimulation may have important implications for human memory research and have far-reaching clinical applications.

Figure 1. Blocking Memory Modification with rTMS during Memory Reactivation

(A) Subjects performed a sequential finger-tapping task in which they had to repeatedly perform with their nondominant left hand a specific constant sequence of finger movements [9, 13] (see Experimental Procedures). (B) Subjects were trained on day 1 and then performed posttraining trials. On day 2, subjects were first tested, and then 1 Hz rTMS was applied to M1 for 15 min containing three reactivation trials of the motor memory. The coil was positioned and maintained online via a stereotactic brain navigation system and each subject’s MRI. Subjects were retested on the third experimental day. (C) Performance improved from posttraining to test (initial consolidation), similar to controls (see Figure S1), however stimulation blocked memory gains between test and retest, blocking modification of the memory. There were significant differences between initial consolidation and memory modification gains. Error bars show SEM. Repeated-measures analysis of variance (ANOVA) and paired t tests were used. **, p < 0.005; *, p < 0.05; N.S. denotes nonsignificance.

Figure 2. Cortical Specificity

(A) 1 Hz rTMS was applied to the vertex control site immediately after the test trials and during the reactivation trials of the motor memory. (B) Performance improved from posttraining to test similar to previous experiments. However, vertex stimulation, contrary to M1 stimulation, did not affect memory modification. Error bars show SEM. **, p < 0.005; *, p < 0.05; N.S. denotes nonsignificance.

Figure 3. Disruption of Performance Per Se during Memory Reactivation Does Not Block Memory Modification

(A) The ulnar nerve at the wrist was stimulated at 1 Hz during the three reactivation trials at an intensity causing an equivalent disruption of performance during reactivation as when M1 was stimulated (see Experimental Procedures). (B) Stimulation did not affect memory modification, as opposed to when M1 was stimulated. Error bars show SEM. **, p < 0.005; *, p < 0.05; N.S. denote nonsignificance.

Figure 4. A Model for Human Motor Memory Modification

The model differentiates not only between functional memory states but also between memory storage domains (see text). Upon memory reactivation, recurrent output from the core storage domain to the primary cortical executing domain which interacts with the environment enables further memory modification. Direct interactions between the core storage domain and the environment not engaging the executing storage domain remain to be determined.