Stimulation of the posterior cingulate impairs episodic memory encoding

Abstract Neuroimaging experiments implicate the posterior cingulate cortex (PCC) in episodic memory processing, making it a potential target for responsive neuromodulation strategies outside of the hippocampal network. However, causal evidence for the role PCC plays in memory encoding is lacking. In patients undergoing seizure mapping, we investigated functional properties of the PCC using deep brain stimulation (DBS) and stereotactic electroencephalography (stereo EEG). These techniques allow precise targeting of deep cortical structures including the PCC, and simultaneous acquisition of oscillatory recordings from neighboring regions such as the hippocampus. We used a free recall experiment in which PCC was stimulated during item encoding period of half of the study lists, while no stimulation was applied during encoding period of the remaining lists. We evaluated if stimulation affected memory and/or modulated hippocampal activity. Results revealed four main findings. (i) Stimulation during encoding impaired memory for early items on the study lists. (ii) Stimulation increased hippocampal gamma band power. (iii) Stimulation-induced gamma power predicted memory impairment. (iv) Functional connectivity between the hippocampus and PCC predicted the degree of stimulation effect on memory. Our findings offer the first causal evidence implicating the PCC in episodic memory encoding. Importantly, results highlight that stimulation targeted outside of the temporal lobe can modulate hippocampal activity with implications on behavior. Furthermore, a-priori measures of connectivity between brain regions within a functional network can be informative in predicting behavioral effects of stimulation. Our findings have significant implications for developing therapie to treat diseases of memory loss and cognitive impairment using DBS. Significance StatementCognitive impairment and memory loss are critical public health challenges. Deep brain stimulation (DBS) is a promising tool for developing strategies to ameliorate memory disorders by targeting brain regions involved in mnemonic processing. Using DBS, our study sheds light on the lesser-known role of the posterior cingulate cortex (PCC) in memory encoding. Stimulating the PCC during encoding impairs subsequent recall memory. The degree of impairment is predictedby stimulation-induced hippocampal gamma oscillations and functional connectivity between PCC and hippocampus. Our findings provide the first causal evidence implicating PCC in memory encoding and highlight the PCC as a favorable target for neuromodulation strategies, using a-priori connectivity measures to predict stimulation effects. This has significant implications for developing therapies for memory diseases.