Low-frequency direct cortical stimulation of left superior frontal gyrus enhances working memory performance

Abstract

The neural substrates of working memory are spread across prefrontal, parietal and cingulate cortices and are thought to be coordinated through low frequency cortical oscillations in the theta (3-8 Hz) and alpha (8-12 Hz) frequency bands. While the functional role of many subregions have been elucidated using neuroimaging studies, the role of superior frontal gyrus (SFG) is not yet clear. Here, we combined electrocorticography and direct cortical stimulation in three patients implanted with subdural electrodes to assess if superior frontal gyrus is indeed involved in working memory. We found left SFG exhibited task-related modulation of oscillations in the theta and alpha frequency bands specifically during the encoding epoch. Stimulation at the frequency matched to the endogenous oscillations resulted in reduced reaction times in all three participants. Our results provide evidence for SFG playing a functional role in working memory and suggest that SFG may coordinate working memory through low-frequency oscillations thus bolstering the feasibility of using intracranial electric stimulation for restoring cognitive function.

Figure 1.

(A) Surface model showing the coverage of electrodes for the three participants. (B) Schematic of a single trial of the working memory task used. The task consisted of 3 epochs - Encoding, Retention and Retrieval. Stimulation was applied through the entire trial. (C) Schematic of the periodic pulse stimulation. Stimulation consisted of train of biphasic pulses 400 μs in duration every 100 ms (P1 and P2) or 200 ms (P3) for 5s.

Figure 2.

(A) Cortical model showing electrodes that exhibited task-related modulation. Red circle denotes the three electrodes in lSFG whose event related spectral perturbation are plotted. observed in left superior frontal gyrus electrodes during sham trials for P1 and baseline session trials for P2 and P3 indicating the modulation of signal in the band 3 – 12 Hz. Hot (red) colors indicate an increase and cold (blue) colors indicate a decrease in signal power relative to baseline. (B) Power spectral density of lSFG electrodes during baseline session in encoding epoch showing peaks that were used to determine stimulation frequency (dotted gray lines) in P2 and P3. (C) Modulation indices during encoding epoch across all lSFG electrodes that exhibited significant task related modulation of signal power. In P1 and P2 there was a significant difference between modulation indices for list length 3 and list length 5.

Figure 3.

(A) Reaction times in trials with 5 items showing a decrease with stimulation. (B) Accuracy was not affected by stimulation (C) Stimulation did not result in any changes in modulation indices in electrodes over lSFG. (D) Differential effect of stimulation on modulation indices in electrodes that exhibited taskrelevant modulation of low frequency oscillations.