Offline persistence of memory-related cerebral activity during active wakefulness

Abstract

Much remains to be discovered about the fate of recent memories in the human brain. Several studies have reported the reactivation of learning-related cerebral activity during post-training sleep, suggesting that sleep plays a role in the offline processing and consolidation of memory. However, little is known about how new information is maintained and processed during post-training wakefulness before sleep, while the brain is actively engaged in other cognitive activities. We show, using functional magnetic resonance imaging, that brain activity elicited during a new learning episode modulates brain responses to an unrelated cognitive task, during the waking period following the end of training. This post-training activity evolves in learning-related cerebral structures, in which functional connections with other brain regions are gradually established or reinforced. It also correlates with behavioral performance. These processes follow a different time course for hippocampus-dependent and hippocampus-independent memories. Our experimental approach allowed the characterization of the offline evolution of the cerebral correlates of recent memories, without the confounding effect of concurrent practice of the learned material. Results indicate that the human brain has already extensively processed recent memories during the first hours of post-training wakefulness, even when simultaneously coping with unrelated cognitive demands.

Figure 1. Experimental Design

All participants underwent four fMRI scanning sessions (I–IV) within a half-day. In scanning session (I), they performed an auditory oddball task during which they mentally counted the number of deviant tones interspersed in a flow of repeated tones. Participants were then trained during 30 min outside of the scanner (training), either to the spatial memory navigation task (red path), or to the procedural memory SRT task (blue path). Immediately after the end of the training session, they were scanned again (II) while performing the auditory oddball task. They were then allowed a further 30-min break outside of the scanner without any further practice (rest). They were scanned once again (III) while performing the auditory oddball task. Afterwards, participants' memory of the learned task was tested outside of the scanner (retest). Finally, participants underwent a fourth fMRI session (IV), during which they explored virtual environments (red path) or practiced motor sequences in the SRT task (blue path), to determine the set of brain areas associated with task practice. The procedure was repeated 2 wk later using the other learning task.

Figure 2. Task-Specific Modulation of Regional Brain Responses by Prior Learning

Spatial learning-related offline activity: (A) Higher brain responses after spatial than after procedural learning in Session II (versus I). Blue cross hair on hippocampus (26 −24 −8 mm) activation superimposed on participants' average anatomical T1-weighted MRI image. (B) Higher brain responses in the parahippocampal gyrus (26 −32 −18 mm) after a further 30-min break during Session III (versus II). (C) Co-occurring decreased brain responses in the hippocampus (22 −22 −10 mm, blue cross hair) during Session III (versus II), more after spatial than after procedural learning. Procedural learning-related offline activity: (D) Higher brain response in the medial cerebellum (2 −60 −28 mm) after procedural than after spatial learning in Session II (versus I). (E) Co-occurring decreased brain responses in the putamen (−20 2 10 mm, blue cross hair), lateral cerebellum, SMA, and other neocortical areas during Session II (versus I), more after procedural than after spatial learning. (F) Higher brain response after a further 30-min break during Session III (versus II) in the caudate nucleus (top: −16 0 16 mm) and the SMA (bottom: 10 2 56 mm). Color bars indicate the magnitude of the effect size, in the yellow range for increased post-training brain response, and in the blue range for decreased post-training brain response.

Figure 3. Practice-Related Activations

(A) Brain activity during exploration of the virtual environment (Session IV). Cross hair shows hippocampus activation (22 −26 −6 mm, p ^corr < 0.005) superimposed on participants' average anatomical T1-weighted MRI image. Color bars indicate magnitude of effect size. (B) Brain activity during practice of the procedural serial RT task (Session IV). Cross hair shows cerebellum activation (12 −74 −22 mm, p ^corr < 0.05).

Figure 4. Offline Modulation of Cerebral Connectivity during Post-Training Wakefulness

Offline spatial learning-related connectivity: (A) Tighter coupling during Session II than during Session I between hippocampus (at coordinate 26 −24 −8 mm) and superior frontal gyrus activity (cross hair at [12 66 16 mm] Z = 3.87; p ^svc(10mm) < 0.05), superimposed on participants' average anatomical T1-weighted MRI image. Color bars indicate magnitude of effect size. (B) Delayed tighter coupling during Session III than during Session I between hippocampus (26 −24 −8 mm) and retrosplenial cortex (cross hair at [8 −48 8 mm]), Z = 3.42, p ^svc(10mm) < 0.05). (C) Offline procedural learning-related connectivity: Delayed enhancement in coupling during Session III as compared to Session I, between cerebellum activity (at coordinate 2 −60 28 mm) and activity in the caudate nucleus (left panel: [−8 2 14 mm] [cross hair], and [−18 −14 24 mm], Z = 3.99 and 3.71, p ^svc(10mm) < 0.05), the putamen ([20 2 −4 mm], data not shown, Z = 3.56, p ^svc(10mm) < 0.05), the lateral cerebellum (middle panel: cross hair at [32 −66 −36 mm], Z = 3.33, p ^svc(10mm) < 0.05), and the dorsal premotor cortex (right panel: cross hair at [−44 10 54 mm], Z = 3.16, trend p ^svc(10mm) = 0.07).

Figure 5. Post-Training Modulation of Neuronal Activity and Behavioral Performance

(A) Activations are superimposed on one participant's T1-weighted normalized MRI image. Left side: Plots of the correlation between changes in spatial performance (distance left to target in learning minus test sessions) and brain response during intervening oddball Session II (versus I; [B]) in the hippocampus ([24 −24 −2 mm], Z = 3.75, p ^svc(10mm) < 0.05) around an a priori location [26 −24 −8 mm]). Each point represents one participant. Part C shows the non-significant correlation ( p > 0.8) at the same location during Session III (versus II). Right side: Plots of the correlation between individual levels of sequence knowledge (RT for novel minus learned sequence) at the end of the Learning phase and brain response during (B) Session II (versus I), showing the non-significant correlation in the left caudate nucleus, and (C) intervening oddball Session III (versus II[C]) in the same location ([−12 −2 20 mm], Z = 4.48, p ^svc < 0.005). r = correlation coefficient.