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

AbstractThe 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.

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A Neuroanatomical Construct for the Amnesic Effects of Propofol

Anesthesiology ◽

10.1097/00000542-200208000-00008 ◽

2002 ◽

Vol 97 (2) ◽

pp. 329-337 ◽

Cited By ~ 50

Author(s):

Robert A. Veselis ◽

Ruth A. Reinsel ◽

Vladimir A. Feshchenko ◽

Ann M. Dnistrian

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Episodic Memory ◽

Temporal Lobe ◽

Medial Temporal Lobe ◽

Regional Cerebral Blood Flow ◽

Memory Task ◽

Statistical Parametric Mapping ◽

Regional Cerebral Blood ◽

Word Memory

Background This study was designed to identify neuroanatomical locations of propofol's effects on episodic memory by producing minimal and maximal memory impairment during conscious sedation. Drug-related changes in regional cerebral blood flow (rCBF) were located in comparison with rCBF increases during a simple word memory task. Methods Regional cerebral blood flow changes were assessed in 11 healthy volunteers using H215O positron emission tomography (PET) and statistical parametric mapping (SPM99) at 600 and 1,000 ng/ml propofol target concentrations. Study groups were based on final recognition scores of auditory words memorized during PET scanning. rCBF changes during propofol administration were compared with those during the word memory task at baseline. Results Nonoverlapping memory effects were evident: low (n = 4; propofol concentration 523 +/- 138 ng/ml; 44 +/- 13% decrement from baseline memory) and high (n = 7; 829 +/- 246 ng/ml; 87 +/- 6% decrement from baseline) groups differed in rCBF reductions primarily in right-sided prefrontal and parietal regions, close to areas activated in the baseline memory task, particularly R dorsolateral prefrontal cortex (Brodmann area 46; x, y, z = 51, 38, 22). The medial temporal lobe region exhibited relative rCBF increases. Conclusions As amnesia becomes maximal, rCBF reductions induced by propofol occur in brain regions identified with working memory processes. In contrast, medial temporal lobe structures were resistant to the global CBF decrease associated with propofol sedation. The authors postulate that the episodic memory effect of propofol is produced by interference with distributed cortical processes necessary for normal memory function rather than specific effects on medial temporal lobe structures.

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Explaining How Brain Stimulation Can Evoke Memories

Journal of Cognitive Neuroscience ◽

10.1162/jocn_a_00170 ◽

2012 ◽

Vol 24 (3) ◽

pp. 553-563 ◽

Cited By ~ 24

Author(s):

Joshua Jacobs ◽

Bradley Lega ◽

Christopher Anderson

Keyword(s):

High School ◽

Temporal Lobe ◽

Brain Stimulation ◽

Neural Activity ◽

Memory Retrieval ◽

Memory Task ◽

Cognitive State ◽

Normal Brain ◽

Neural Basis ◽

Neurosurgical Patients

An unexplained phenomenon in neuroscience is the discovery that electrical stimulation in temporal neocortex can cause neurosurgical patients to spontaneously experience memory retrieval. Here we provide the first detailed examination of the neural basis of stimulation-induced memory retrieval by probing brain activity in a patient who reliably recalled memories of his high school (HS) after stimulation at a site in his left temporal lobe. After stimulation, this patient performed a customized memory task in which he was prompted to retrieve information from HS and non-HS topics. At the one site where stimulation evoked HS memories, remembering HS information caused a distinctive pattern of neural activity compared with retrieving non-HS information. Together, these findings suggest that the patient had a cluster of neurons in his temporal lobe that help represent the “high school-ness” of the current cognitive state. We believe that stimulation here evoked HS memories because it altered local neural activity in a way that partially mimicked the normal brain state for HS memories. More broadly, our findings suggest that brain stimulation can evoke memories by recreating neural patterns from normal cognition.

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Time cells in the human hippocampus and entorhinal cortex support episodic memory

10.1101/2020.02.03.932749 ◽

2020 ◽

Cited By ~ 3

Author(s):

Gray Umbach ◽

Pranish Kantak ◽

Joshua Jacobs ◽

Michael Kahana ◽

Brad E. Pfeiffer ◽

...

Keyword(s):

Episodic Memory ◽

Entorhinal Cortex ◽

Cell Activity ◽

Memory Task ◽

Temporal Information ◽

Temporal Organization ◽

Human Epilepsy ◽

Human Hippocampus ◽

Phase Precession ◽

Episodic Memories

AbstractThe organization of temporal information is critical for the encoding and retrieval of episodic memories. In the rodent hippocampus and entorhinal cortex, recent evidence suggests that temporal information is encoded by a population of “time cells.” We identify time cells in humans using intracranial microelectrode recordings obtained from 27 human epilepsy patients who performed an episodic memory task. We show that time cell activity predicts the temporal organization of episodic memories. A significant portion of these cells exhibits phase precession, a key phenomenon not previously seen in human recordings. These findings establish a cellular mechanism for the representation of temporal information in the human brain needed to form episodic memories.

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Functional wiring of the human medial temporal lobe

10.1101/257899 ◽

2018 ◽

Cited By ~ 4

Author(s):

E. A. Solomon ◽

J. M. Stein ◽

S. Das ◽

R. Gorniak ◽

M. R. Sperling ◽

...

Keyword(s):

Functional Connectivity ◽

Episodic Memory ◽

Temporal Lobe ◽

Medial Temporal Lobe ◽

Memory Task ◽

Memory Processing ◽

High Frequencies ◽

Functional Connections ◽

Brain Functions ◽

Encoding And Retrieval

AbstractThe medial temporal lobe (MTL) is a locus of episodic memory in the human brain. It is comprised of cytologically distinct subregions that, in concert, give rise to successful encoding and retrieval of context-dependent memories. However, the functional connections between these subregions are poorly understood. To determine functional connectivity among MTL subregions, we had 126 subjects fitted with indwelling electrodes perform a verbal memory task, and asked how encoding or retrieval correlated with interregional synchronization. Using phase-based measures of connectivity, we found that synchronous theta (4-8 Hz) activity underlies successful episodic memory, whereas high-frequencies exhibit desynchronization. Moreover, theta functional connectivity during encoding aligned with key anatomic connections, including critical links between the entorhinal cortex, dentate gyrus, and CA1 of the hippocampus. Retrieval-associated networks demonstrated enhanced involvement of the subiculum, reflecting a substantial reorganization of the encoding-associated network. We posit that coherent theta activity within the MTL marks periods of successful memory, but distinct patterns of connectivity dissociate key stages of memory processing.Significance StatementThe brain functions through the interaction of its distinct parts, but little is known about how such connectivity dynamics relate to learning and memory. We used a large dataset of 126 human subjects with intracranial electrodes to assess patterns of electrical connectivity within the medial temporal lobe – a key region for memory processing – as they performed a memory task. We discovered that unique networks of time-varying, low-frequency interactions correlate with memory encoding and retrieval, specifically in the theta band. Simultaneously, we observed elevated spectral power at high frequencies in these same regions. The result is a complete map of physiological dynamics within the MTL, highlighting how a reorganization of theta networks support distinct memory operations.

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Time cells in the human hippocampus and entorhinal cortex support episodic memory

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2013250117 ◽

2020 ◽

Vol 117 (45) ◽

pp. 28463-28474 ◽

Cited By ~ 1

Author(s):

Gray Umbach ◽

Pranish Kantak ◽

Joshua Jacobs ◽

Michael Kahana ◽

Brad E. Pfeiffer ◽

...

Keyword(s):

Episodic Memory ◽

Entorhinal Cortex ◽

Cell Activity ◽

Memory Task ◽

Cellular Mechanism ◽

Temporal Information ◽

Temporal Organization ◽

Human Epilepsy ◽

Human Hippocampus ◽

Episodic Memories

The organization of temporal information is critical for the encoding and retrieval of episodic memories. In the rodent hippocampus and entorhinal cortex, evidence accumulated over the last decade suggests that populations of “time cells” in the hippocampus encode temporal information. We identify time cells in humans using intracranial microelectrode recordings obtained from 27 human epilepsy patients who performed an episodic memory task. We show that time cell activity predicts the temporal organization of retrieved memory items. We also uncover evidence of ramping cell activity in humans, which represents a complementary type of temporal information. These findings establish a cellular mechanism for the representation of temporal information in the human brain needed to form episodic memories.

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Children show adult-like hippocampal pattern separation for familiar but not novel events

10.31234/osf.io/3d8tv ◽

2020 ◽

Author(s):

Susan L. Benear ◽

Elizabeth A. Horwath ◽

Emily Cowan ◽

M. Catalina Camacho ◽

Chi Ngo ◽

...

Keyword(s):

Episodic Memory ◽

Temporal Lobe ◽

Medial Temporal Lobe ◽

Developmental Change ◽

Pattern Separation ◽

Developmental Changes ◽

Similarity Analysis ◽

Separation Processes ◽

Parahippocampal Cortex ◽

Pattern Similarity

The medial temporal lobe (MTL) undergoes critical developmental change throughout childhood, which aligns with developmental changes in episodic memory. We used representational similarity analysis to compare neural pattern similarity for children and adults in hippocampus and parahippocampal cortex during naturalistic viewing of clips from the same movie or different movies. Some movies were more familiar to participants than others. Neural pattern similarity was generally lower for clips from the same movie, indicating that related content taxes pattern separation-like processes. However, children showed this effect only for movies with which they were familiar, whereas adults showed the effect consistently. These data suggest that children need more exposures to stimuli in order to show mature pattern separation processes.

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Early stages of tau pathology and its associations with functional connectivity, atrophy and memory

Brain ◽

10.1093/brain/awab114 ◽

2021 ◽

Author(s):

David Berron ◽

Jacob W Vogel ◽

Philip S Insel ◽

Joana B Pereira ◽

Long Xie ◽

...

Keyword(s):

Functional Connectivity ◽

Entorhinal Cortex ◽

Temporal Lobe ◽

Medial Temporal Lobe ◽

Memory Impairment ◽

Memory Performance ◽

Hippocampal Atrophy ◽

Tau Pathology ◽

Β Amyloid ◽

With Memory

Abstract In Alzheimer’s disease, postmortem studies have shown that the first cortical site where neurofibrillary tangles appear is the transentorhinal region, a subregion within the medial temporal lobe that largely overlaps with area 35, and the entorhinal cortex. Here we used tau-PET imaging to investigate the sequence of tau pathology progression within the human medial temporal lobe and across regions in the posterior-medial system. Our objective was to study how medial temporal tau is related to functional connectivity, regional atrophy, and memory performance. We included 215 β-amyloid negative cognitively unimpaired, 81 β-amyloid positive cognitively unimpaired and 87 β-amyloid positive individuals with mild cognitive impairment, who each underwent [18]F-RO948 tau and [18]F-flutemetamol amyloid PET imaging, structural T1-MRI and memory assessments as part of the Swedish BioFINDER-2 study. First, event-based modelling revealed that the entorhinal cortex and area 35 show the earliest signs of tau accumulation followed by the anterior and posterior hippocampus, area 36 and the parahippocampal cortex. In later stages, tau accumulation became abnormal in neocortical temporal and finally parietal brain regions. Second, in cognitively unimpaired individuals, increased tau load was related to local atrophy in the entorhinal cortex, area 35 and the anterior hippocampus and tau load in several anterior medial temporal lobe subregions was associated with distant atrophy of the posterior hippocampus. Tau load, but not atrophy, in these regions was associated with lower memory performance. Further, tau-related reductions in functional connectivity in critical networks between the medial temporal lobe and regions in the posterior-medial system were associated with this early memory impairment. Finally, in patients with mild cognitive impairment, the association of tau load in the hippocampus with memory performance was partially mediated by posterior hippocampal atrophy. In summary, our findings highlight the progression of tau pathology across medial temporal lobe subregions and its disease-stage specific association with memory performance. While tau pathology might affect memory performance in cognitively unimpaired individuals via reduced functional connectivity in critical medial temporal lobe-cortical networks, memory impairment in mild cognitively impaired patients is associated with posterior hippocampal atrophy.

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Modulation of medial temporal lobe activity in epilepsy patients with hippocampal sclerosis during verbal working memory

Journal of the International Neuropsychological Society ◽

10.1017/s135561770909078x ◽

2009 ◽

Vol 15 (4) ◽

pp. 536-546 ◽

Cited By ~ 10

Author(s):

PABLO CAMPO ◽

FERNANDO MAESTÚ ◽

IRENE GARCÍA-MORALES ◽

ANTONIO GIL-NAGEL ◽

BRYAN STRANGE ◽

...

Keyword(s):

Working Memory ◽

Episodic Memory ◽

Temporal Lobe ◽

Medial Temporal Lobe ◽

Time Course ◽

Hippocampal Sclerosis ◽

Stimulus Presentation ◽

Verbal Working Memory ◽

Compelling Evidence ◽

Electrophysiological Studies

AbstractIt has been traditionally assumed that medial temporal lobe (MTL) is not required for working memory (WM). However, animal lesion and electrophysiological studies and human neuropsychological and neuroimaging studies have provided increasing evidences of a critical involvement of MTL in WM. Based on previous findings, the central aim of this study was to investigate the contribution of the MTL to verbal WM encoding. Here, we used magnetoencephalography (MEG) to compare the patterns of MTL activation of 9 epilepsy patients suffering from left hippocampal sclerosis with those of 10 healthy matched controls while they performed a verbal WM task. MEG recordings allow detailed tracking of the time course of MTL activation. We observed impaired WM performance associated with changes in the dynamics of MTL activity in epilepsy patients. Specifically, whereas patients showed decreased activity in damaged MTL, activity in the contralateral MTL was enhanced, an effect that became significant in the 600- to 700-ms interval after stimulus presentation. These findings strongly support the crucial contribution of MTL to verbal WM encoding and provide compelling evidence for the proposal that MTL contributes to both episodic memory and WM. Whether this pattern is signaling reorganization or a normal use of a damaged structure is discussed. (JINS, 2009, 15, 536–546.)

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Egocentric Navigation Abilities Predict Episodic Memory Performance

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2020.574224 ◽

2020 ◽

Vol 14 ◽

Author(s):

Giorgia Committeri ◽

Agustina Fragueiro ◽

Maria Maddalena Campanile ◽

Marco Lagatta ◽

Ford Burles ◽

...

Keyword(s):

Episodic Memory ◽

Semantic Memory ◽

Path Integration ◽

Medial Temporal Lobe ◽

Declarative Memory ◽

Memory Performance ◽

Memory Task ◽

Recognition Task ◽

Future Research ◽

Egocentric Navigation

The medial temporal lobe supports both navigation and declarative memory. On this basis, a theory of phylogenetic continuity has been proposed according to which episodic and semantic memories have evolved from egocentric (e.g., path integration) and allocentric (e.g., map-based) navigation in the physical world, respectively. Here, we explored the behavioral significance of this neurophysiological model by investigating the relationship between the performance of healthy individuals on a path integration and an episodic memory task. We investigated the path integration performance through a proprioceptive Triangle Completion Task and assessed episodic memory through a picture recognition task. We evaluated the specificity of the association between performance in these two tasks by including in the study design a verbal semantic memory task. We also controlled for the effect of attention and working memory and tested the robustness of the results by including alternative versions of the path integration and semantic memory tasks. We found a significant positive correlation between the performance on the path integration the episodic, but not semantic, memory tasks. This pattern of correlation was not explained by general cognitive abilities and persisted also when considering a visual path integration task and a non-verbal semantic memory task. Importantly, a cross-validation analysis showed that participants' egocentric navigation abilities reliably predicted episodic memory performance. Altogether, our findings support the hypothesis of a phylogenetic continuity between egocentric navigation and episodic memory and pave the way for future research on the potential causal role of egocentric navigation on multiple forms of episodic memory.

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