Electrical stimulation in hippocampus and entorhinal cortex impairs spatial and temporal memory

Abstract

The medial temporal lobe (MTL) is widely implicated in supporting episodic memory and navigation, but its precise functional role in organizing memory across time and space remains elusive. Here we examine the specific cognitive processes implemented by MTL structures (hippocampus and entorhinal cortex) to organize memory by using electrical brain stimulation, leveraging its ability to establish causal links between brain regions and features of behavior. We studied neurosurgical patients of both sexes who performed spatial-navigation and verbal-episodic memory tasks while brain stimulation was applied in various regions during learning. During the verbal memory task, stimulation in the MTL disrupted the temporal organization of encoded memories such that items learned with stimulation tended to be recalled in a more randomized order. During the spatial task, MTL stimulation impaired subjects’ abilities to remember items located far away from boundaries. These stimulation effects were specific to the MTL. Our findings thus provide the first causal demonstration in humans of the specific memory processes that are performed by the MTL to encode when and where events occurred.Significance StatementNumerous studies have implicated the medial temporal lobe (MTL) in encoding spatial and temporal memories, but they have not been able to causally demonstrate the nature of the cognitive processes by which this occurs in real-time. Electrical brain stimulation is able to demonstrate causal links between a brain region and a given function with high temporal precision. By examining behavior in a memory task as subjects received MTL stimulation, we provide the first causal evidence demonstrating the role of the MTL in organizing the spatial and temporal aspects of episodic memory.

Stimulation of the posterior cingulate impairs episodic memory encoding

“…What is the role of the PCC in memory encoding? Stimulating the hippocampus and medial temporal lobe leads to a global decline in all facets of episodic memory including memory for primacy items, and temporal and semantic clustering scores (11,15). This result is consistent with these regions' critical roles in mnemonic processes and encoding of episodic concepts (55).…”

“…Thus, in contrast to recall performance and primacy that decreased when PCC was stimulated, associative memory processes including the TCF and SCF remain largely unaffected. This result is different than that observed when stimulating core memory regions including the entorhinal cortex and hippocampus as stimulation in these sites disrupts all aspects of memory processing including temporal clustering (11,15).…”

“…Each word in the study list was presented for 1500 ms, followed by a blank screen for 1000 ms. Stimulation to the PCC was applied during the entire duration of the encoding phase of a study list, for half of the total number of study lists (we refer to these lists as stimulation during encoding (ES) lists), while no stimulation was applied during encoding phase of the remaining word lists (we refer to these lists as no stimulation (NS) lists). As compared to prior studies that applied stimulation during encoding of alternate pairs of study items within each study list (11,15), in our experiment, stimulation to PCC was delivered throughout the encoding period in a random order to largely avoid concerns of post--stimulation electrophysiological changes impacting oscillatory patterns of nearby items.…”

“…Recently, a large number of studies have applied DBS in patients undergoing treatments for epilepsy for probing core regions involved in memory processing, including the hippocampus, entorhinal cortex, and lateral temporal lobe and for understanding the effects of stimulation on memory performance (7--14). Results predominantly show that applying electrical stimulation to the hippocampus and entorhinal cortex impairs memory (11,15) (with some exceptions (10)), providing evidence for causal role of these regions in mnemonic processing. This makes DBS ideal for studying cognitive enhancement and causal roles of deep cortical structures associated with memory (7--14, 16) and sensory processes (17,18) as well as for developing neuromodulation strategies to treat memory and motors disorders (19).…”

Increased task-dependent functional connectivity by stimulation of the hippocampal network predicts memory enhancement

“…given that increased connectivity due to stimulation should manifest primarily during memory 42 processing that depends on the network, and such task-dependent modulation would be essential 43 for any effective intervention intended to improve memory ability. 44 Invasive stimulation of the hippocampus or its direct mesial-temporal afferents has 45 primarily been associated with memory disruption [12][13][14] . However, the hippocampal network can 46 serve as a target for memory improvement [15][16][17][18] .…”