Dual transcranial electromagnetic stimulation of the precuneus boosts human long-term memory
- Experimental Neuropsychophysiology Laboratory, Santa Lucia Foundation IRCCS, Italy
- Department of Neuroscience and Rehabilitation, University of Ferrara, and Center for Translational Neurophysiology of Speech and Communication (CTNSC), Italian Institute of Technology (IIT), Italy
- Department of System Medicine, “Tor Vergata” University of Rome, Italy
Figures
Figure 1 with 3 supplements
Individual target extraction and experimental design.
(A) Methodological workflow used to extract the individualized target for the neuromodulation protocol used in experiments 1, 3, and 4. Participants underwent functional MRI (fMRI) scanning to individualize the stimulation sites and permit neuronavigation. Target individualization was derived by computing a PC functional connectivity profile for each participant, thus obtaining a map of positively correlated voxels, respectively, representing the DMN (panel A, left). The individual stimulation targets were defined as the centroid of the strongest PC activation being on the top of a cortical gyrus and representing the shortest perpendicular path connecting the stimulating TMS coil on the scalp and the cortex (panel A, center). PC coordinates for each participant are represented in red on an MNI brain template, showing the overlap with the DMN (panel A, right). (B) Biophysical modeling was computed for each subject, acquiring T1w and T2w MRI and using the SimNIBS toolbox for the T1w segmentation and the 3D-mesh transformation (panel B, left). The mean Norm e-field was extracted from a target region of interest (ROI) sphere (10 mm radius) centered on the individual coordinates of the PC (panel B, center). The simulated induced electric field is shown for a representative subject produced by iTBS (e-field modeling, left) and transcranial alternating current stimulation (tACS; e-field modeling, right). EEG source activity reconstruction induced by the TMS pulse over the precuneus in a representative subject (panel B, right). Experimental design of experiments 1 (C), 2 (D), 3 (E), and 4 (F). The effect of simultaneous iTBS + γtACS on memory performance was investigated in experiments 1 (C) and 2 (D) through two memory tasks: the face–name associative task (FNAT), which required the memorization of 12 faces with corresponding names and occupations, and the visual short-term memory binding test (STMB), which consisted of a change detection task. In the main experiment 1 (C), subjects were involved in a cross-over design with different experimental sessions of neuromodulation separated by a washout week. Every session corresponded to a different balanced and randomized stimulation condition (i.e., iTBS + γtACS, iTBS + sham-tACS, sham-iTBS + sham-γtACS) immediately followed by the FNAT learning phase and immediate recall, the STMB and the FNAT delayed recall (15 min delayed) and recognition. In experiment 2 (D), subjects were involved in a cross-over design with two balanced and randomized stimulation conditions (i.e., iTBS + γtACS, iTBS + sham-tACS) separated by a washout week. During the first session (day 1), participants received the neuromodulation protocol and then performed the learning phase and immediate recall FNAT, the STMB, and the FNAT delayed recall. In the second session (day 2), participants performed FNAT recall with a 24-hr delay from the neuromodulation protocol, while in the third session (day 7), participants performed FNAT recall and recognition with a 1-week delay. In experiment 3 (E), participants were involved in two randomized and balanced experimental sessions of neuromodulation (i.e., iTBS + γtACS, iTBS + sham-tACS) separated by a washout week. TMS–EEG recordings were performed before (T0), immediately after (T1), and 20 min after the neuromodulation (T2). In experiment 4 (D), after the first MRI scanning used for neuronavigation, participants were involved in two randomized and balanced experimental sessions of neuromodulation (i.e., iTBS + γtACS, iTBS + sham-tACS) separated by a washout week. The fMRI scanning was performed before (T0) and immediately after (T1) the neuromodulation protocol. Photographs reported represent the author Michele Maiella performing the task and an example of the face item used in the task taken from the FACES database (Ebner et al., 2010).
© 2010, Max Planck Institute for Human Development. Facial images in Figure 1 are from the FACES database. It is not covered by the CC-BY 4.0 licence and further reproduction of this panel would need permission from the copyright holder.
Figure 1—figure supplement 1
TMS and transcranial alternating current stimulation (tACS) e-field simulation.
Figure S1 shows the e-field for a representative subject. Panel (A) shows the TMS e-field, while panel (B) shows tACS e-field simulation.
Figure 1—figure supplement 2
Face–name associative task (FNAT).
Panel (A) shows FNAT steps implemented in experiment 1 consisting of a learning phase followed by immediate cued recall and a 15-min delayed cued recall with recognition. Panel (B) shows the variation of FNAT implemented in experiment 2, where the learning phase was followed by an immediate cued recall and a 15-min delayed recall on day 1, a 24-hr delayed cued recall on day 2, and a 1-week delayed cued recall with recognition on day 7.
© 2010, Max Planck Institute for Human Development. Facial images in Figure 1-figure supplement 2 are from the FACES database. It is not covered by the CC-BY 4.0 licence and further reproduction of this panel would need permission from the copyright holder.
Figure 1—figure supplement 3
Short-term memory binding task (STMB).
Panel (A) represents the STMB for the shapes only, while panel (B) represents STMB for shapes and colors. Both versions consist of a study phase (up) lasting 2 s, followed by a retention phase (center) lasting 1 s, and a test phase (down) where the participants have to decide if the items shown are the same or different from the learning phase. Panel (C) shows the perception trial, where two arrays of shapes are presented at the same time and participants have to answer if they are the same or different.
Figure 2 with 1 supplement
Memory performance outcome.
The figure shows the results of the repeated measures ANOVA performed to analyze memory performance outcomes. In the Box and Whiskers plots, boxes delimit the lower (Q1) and the upper (Q3) quartiles, the whiskers extend to the smallest and largest values, and dots represent individual values. In the line graphs, colored dots show individual participant data, lines show the connection between the performances of each participant, and black dots and lines correspond to the mean performance values. Gray corresponds to iTBS + sham-tACS, blue to sham-iTBS + sham-tACS and red to iTBS + γtACS. *p < 0.05. (A) Face–name associative task (FNAT) accuracy in immediate (right) and delayed (left) trials resulting from experiment 1. N = 20. (B) Short-term memory binding task RTs (left) and accuracy (right) resulting from experiment 1. N = 20. (C) FNAT’s long-lasting effect resulted from experiment 2. The results are shown over time (days 1, 2, and 7). N = 10.
Figure 2—figure supplement 1
Face–name associative task (FNAT) in-depth analysis.
The figure shows the results of the repeated measures ANOVA performed to analyze in-depth FNAT accuracy for the association of face with name (NAME) and face with occupation (OCCUPATION). The first row shows the performances in immediate and delayed trials resulting from experiment 1 (N = 20). The second row shows the performances in the delayed trials resulting from experiment 2 (N = 10). Boxes delimit the lower (Q1) and the upper (Q3) quartiles, whiskers extend to the smallest and largest values, and dots represent individual values. Gray corresponds to iTBS + sham-tACS, blue to sham-iTBS +sham-tACS and red to iTBS + γtACS. *p < 0.05.
Figure 3
Experiment 3 neurophysiological outcome.
(A) Precuneus (PC) oscillatory activity elicited by iTBS + γtACS (up) and iTBS + sham-tACS (down) when testing PC over the three time points (T0, T1, T2 from left to right) with repeated measures ANOVA. (B) Gamma oscillation changes from baseline after iTBS + γtACS (red) and iTBS + sham-tACS (gray). (C) TMS-evoked potential (TEP) produced over the PC when performing TMS–EEG over PC in the two stimulation conditions: iTBS+γtACS (up-left) and iTBS + sham-tACS (up-right) over the three time points (T0, T1, T2). (Down) Topographies and statistical differences in TEPs amplitude after the different stimulation conditions (iTBS + γtACS, left; iTBS + sham-tACS, right) over the three time points (T0, T1, T2, from left to right). N = 14; *p < 0.05; bars depict standard error.
Figure 4
Resting-state functional connectivity (rs-FC) changes after iTBS + γtACS and correlation with Diffusion Tensor Images (DTI).
(A) The standard MNI brain (left) and the bar plot (right) display the positive correlation between the PC and the bilateral HIP after the iTBS + γtACS resulted from the region of interest (ROI)-to-ROI analysis. (B) Seed-to-voxel analysis results from each significant ROI (i.e., left HIP, left; PC, center; right HIP, right) are overlaid on a standard MNI brain. (C) Middle Longitudinal Fasciculus (MdLF) extracted (left); positive correlation between MdLF integrity and functional connectivity changes between the PC and bilateral HIP after iTBS + γtACS (upper right); the absence of correlation in the iTBS +sham-tACS condition and functional connectivity (lower right). N = 16; *p < 0.05; bars depict standard error.
Videos
Video 1
TMS–EEG source reconstruction.
The movie shows the source reconstruction of the TMS–EEG signal when targeting the precuneus. The three columns correspond to the recordings conducted before, just after, and 20 min from the non-invasive brain stimulation protocol (i.e., T0, T1, and T2). The first row corresponds to the iTBS + γtACS condition, while the second to the iTBS + sham-tACS condition.
Additional files
-
Supplementary file 1
Experiment 1 statistical details of the face–name associative task (FNAT) and short-term memory binding test (STMB).
- https://cdn.elifesciences.org/articles/104220/elife-104220-supp1-v1.docx
-
Supplementary file 2
Experiment 2 statistical details of the immediate and recognition face–name associative task (FNAT) and short-term memory binding test (STMB).
- https://cdn.elifesciences.org/articles/104220/elife-104220-supp2-v1.docx
-
Supplementary file 3
Experiment 2 statistical details of the delayed face–name associative task (FNAT).
- https://cdn.elifesciences.org/articles/104220/elife-104220-supp3-v1.docx
-
Supplementary file 4
Demographic characteristics.
- https://cdn.elifesciences.org/articles/104220/elife-104220-supp4-v1.rtf
-
Supplementary file 5
Subject-specific information about stimulation parameters and e-field calculations.
- https://cdn.elifesciences.org/articles/104220/elife-104220-supp5-v1.docx
-
MDAR checklist
- https://cdn.elifesciences.org/articles/104220/elife-104220-mdarchecklist1-v1.docx
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Dual transcranial electromagnetic stimulation of the precuneus boosts human long-term memory
eLife 14:RP104220.
https://doi.org/10.7554/eLife.104220.4
