Closed-loop stimulation of temporal cortex rescues functional networks and improves memory

Abstract

Memory failures are frustrating and often the result of ineffective encoding. One approach to improving memory outcomes is through direct modulation of brain activity with electrical stimulation. Previous efforts, however, have reported inconsistent effects when using open-loop stimulation and often target the hippocampus and medial temporal lobes. Here we use a closed-loop system to monitor and decode neural activity from direct brain recordings in humans. We apply targeted stimulation to lateral temporal cortex and report that this stimulation rescues periods of poor memory encoding. This system also improves later recall, revealing that the lateral temporal cortex is a reliable target for memory enhancement. Taken together, our results suggest that such systems may provide a therapeutic approach for treating memory dysfunction.

Fig. 1

Closed-loop approach. a For each list of the free recall task, subjects encoded 12 nouns presented sequentially, followed by an arithmetic distractor and the verbal recall phase. Subjects performed at least three sessions of record-only free recall. b After the record-only sessions, we use spectral decomposition to measure power at a set of frequencies ranging from 3 to 180 Hz for each encoded word. We used the patterns of spectral power across electrodes to train a penalized logistic regression classifier to discriminate encoding activity during subsequently recalled words from subsequently forgotten words. c In later closed-loop sessions, we applied spectral decomposition to each word encoding period while subjects performed the task. This produced a set of frequency × electrode features to which we applied the classifier trained on the record-only data. If the resulting estimated probability of recall was below 0.5, we triggered 500 ms of stimulation to either the lateral temporal cortex or a control target

Fig. 2

Classifier performance and features. a Receiver operating characteristic (ROC) curves showing performance of a record-only classifier tested on NoStim lists during the closed-loop sessions (gray lines). Each curve displays the ROC for a unique subject–stimulation site. The group average is shown in red (mean AUC = 0.61, P < 10⁻⁷ by a one-sample t-test, N = 29 unique stimulation targets). b Forward model-based estimates of feature importance. For each electrode region by frequency feature, we computed a forward model-based estimate of the feature’s contribution to the classification decision. This analysis shows that the classifier used increased high-frequency power combined with decreased low-frequency power to predict successfully recalled words (clusters significant at the P < 0.05 level by a one-sample t-test are outlined in gray, N =  25 record-only classifiers)

Fig. 3

Stimulation affects behavior and physiology. a Stimulation delivered to lateral temporal cortex targets increased the probability of recall compared to matched unstimulated words in the same subject (P < 0.05) and stimulation delivered to Non-lateral temporal targets in an independent group (P < 0.01). b The change in classifier output post-lateral temporal cortex stimulation was greater than for matched intervals on NoStim lists. Data are presented as model parameter estimate ± SE. Lateral temporal cortex N = 18; Non-lateral temporal N = 11

Fig. 4

Stimulation targets rendered on an average brain surface. Targets showing numerical increase/decrease in free recall performance are shown in red/blue. Memory-enhancing sites clustered in the middle portion of the left middle temporal gyrus (coordinate range X : − 67 to − 47; Y : − 51 to − 1; Z : − 33 to 8)