Electrical Stimulation Modulates High γ Activity and Human Memory Performance

Abstract

Direct electrical stimulation of the brain has emerged as a powerful treatment for multiple neurological diseases, and as a potential technique to enhance human cognition. Despite its application in a range of brain disorders, it remains unclear how stimulation of discrete brain areas affects memory performance and the underlying electrophysiological activities. Here, we investigated the effect of direct electrical stimulation in four brain regions known to support declarative memory: hippocampus (HP), parahippocampal region (PH) neocortex, prefrontal cortex (PF), and lateral temporal cortex (TC). Intracranial EEG recordings with stimulation were collected from 22 patients during performance of verbal memory tasks. We found that high γ (62-118 Hz) activity induced by word presentation was modulated by electrical stimulation. This modulatory effect was greatest for trials with "poor" memory encoding. The high γ modulation correlated with the behavioral effect of stimulation in a given brain region: it was negative, i.e., the induced high γ activity was decreased, in the regions where stimulation decreased memory performance, and positive in the lateral TC where memory enhancement was observed. Our results suggest that the effect of electrical stimulation on high γ activity induced by word presentation may be a useful biomarker for mapping memory networks and guiding therapeutic brain stimulation.

Keywords: ECoG; brain stimulation; cognitive enhancement; high-frequency oscillations; intracranial EEG; γ-activity.

Graphical abstract

Figure 1.

Free recall tasks to study electrophysiological modulation of verbal memory encoding. A, Diagram of the task design, in which subjects memorized word lists for subsequent recall. Thunderbolt marks the words with stimulation on the STIM lists. The remaining word trials were used for electrophysiological analysis and are labeled according to the lists type (NON-STIM or STIM) and their encoding based on subsequent recall (GOOD or POOR). B, Example of an 8 × 8 electrode grid implanted over the lateral TC highlights in red two adjacent contacts used for brain stimulation (connected red dots) in subject 1050. C, Broadband spectrogram (left column) shows trial-averaged power changes aligned to the time of word presentation for encoding, in contrast to the power changes in the signal prefiltered in the four studied frequency bands (middle column), as recorded from a representative electrode example from subject 1111. Line plots on the right summarize the mean power change response independently for the four bands (rows) and separately for the good and poor encoding trials (columns) in the two conditions of list stimulation, color-coded as in A. Notice the difference in peaks of the response (NM index) caused by stimulation in the poor encoding trials specifically in the high γ frequency band.

Figure 2.

Stimulation modulates high γ responses in localized areas activated in the tasks. A, Values of the peak power of the γ responses and the NM index from all 8 × 8 grid electrodes (blue dots, stimulating electrodes in red) of subject 1050, as in Figure 1B, are interpolated and visualized as surface plots overlaid on this subject's brain surface (left side). The first two columns present peaks of the high γ power in the STIM (first) and the NON-STIM (second) conditions, the third column presents the NM index, i.e., the effective difference between the first two columns. Arrows point to a discrete area of peak power modulated by stimulation particularly in the poor encoding trials. B, C, Analogous plots from two other cases of subject 1111 (brain surface rendering was turned upside down to aid visualization) and 1177, respectively. Notice that the high γ modulation is observed also at a distance from the stimulation site in subject 1111 and is not observed in subject 1177.

Figure 3.

Stimulation selectively modulates task responses in the high γ frequency band. A, Spectrogram of trial-averaged high γ response to word presentations recorded on an electrode in the brain area activated in the tasks. B, Active electrodes showing this response were identified as positive outliers of the peak value distribution of this response (red data points above the solid line of UAV). C, Mean NM index of all active electrodes in one stimulated patient (n = 36) is compared among four frequency bands in the poor and good memory encoding conditions. Subplots on the right show post hoc comparison of the group means, dashed lines mark the 95% CI intervals (error bars) for the high γ group, and red indicates significant group with the intervals that do not overlap with any other group. D, Scatterplots with least-square lines show correlations of the NM index values in the poor encoding condition plotted against peak value of the task response (left) and against the distance from the stimulation site (right) for the active electrodes from C. Notice that NM index was proportional to the induced power response and inversely proportional to the distance from the stimulation site.

Figure 4.

High γ responses are positively and negatively modulated in different brain regions. Four electrode examples show modulation of the task-induced high γ activities by stimulation in the lateral TC (red) and the HP (green), as presented in another example from Figure 1C. Arrows mark the positive and negative NM index changes in the three patients who showed the greatest positive (upper rows) and negative (lower rows) behavioral effects of stimulation (Fig. 5).

Figure 5.

Modulation of high γ activity in different brain regions is correlated with behavior. A, Localization of the stimulation sites in the lateral TC (red contact pairs) and the other three brain regions studied (black contact pairs) is visualized in a unified transparent brain surface. B, Stimulation-induced change in memory performance for every subject (each bar is one subject) reveals that stimulation in the TC had a positive effect on performance compared to the other brain regions (PF). Post hoc group comparison (right side) shows that TC scores are greater than PH, HP, PF (dashed lines are 95% CI of the TC group). C, NM index values reveal the same pattern as in B, averaged from all active electrodes in a given group [n = 38 (PH), n = 80 (HP), n = 36 (TC), n = 44 (PFC)]. D, The behavioral and NM index scores averaged for each subject (color-coded dots) are correlated. Least-square line is added in black, crossing the two dashed lines at point 0 indicating no stimulation-induced changes.