Intracranial EEG Correlates of Expectancy and Memory Formation in the Human Hippocampus and Nucleus Accumbens

The nucleus accumbens (NAc) serves as a key neural substrate for aversive learning and consists of two distinct subpopulations of medium-sized spiny neurons (MSNs). The MSNs of the direct pathway (dMSNs) and the indirect pathway (iMSNs) predominantly express dopamine (DA) D1 and D2 receptors, respectively, and are positively and negatively modulated by DA transmitters via Gs- and Gi-coupled cAMP-dependent protein kinase A (PKA) signaling cascades, respectively. In this investigation, we addressed how intracellular PKA signaling is involved in aversive learning in a cell type-specific manner. When the transmission of either dMSNs or iMSNs was unilaterally blocked by pathway-specific expression of transmission-blocking tetanus toxin, infusion of PKA inhibitors into the intact side of the NAc core abolished passive avoidance learning toward an electric shock in the indirect pathway-blocked mice, but not in the direct pathway-blocked mice. We then examined temporal changes in PKA activity in dMSNs and iMSNs in behaving mice by monitoring Förster resonance energy transfer responses of the PKA biosensor with the aid of microendoscopy. PKA activity was increased in iMSNs and decreased in dMSNs in both aversive memory formation and retrieval. Importantly, the increased PKA activity in iMSNs disappeared when aversive memory was prevented by keeping mice in the conditioning apparatus. Furthermore, the increase in PKA activity in iMSNs by aversive stimuli reflected facilitation of aversive memory retention. These results indicate that PKA signaling in iMSNs plays a critical role in both aversive memory formation and retention.

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Hippocampal theta oscillations support successful associative memory formation

10.1101/2020.05.26.116517 ◽

2020 ◽

Author(s):

Srinivas Kota ◽

Michael D. Rugg ◽

Bradley C. Lega

Keyword(s):

Associative Memory ◽

Memory Formation ◽

Associative Recognition ◽

Theta Oscillations ◽

Memory Encoding ◽

Phase Reset ◽

Intracranial Eeg ◽

Electrophysiological Evidence ◽

Hippocampal Theta ◽

Encoding And Retrieval

1.AbstractModels of memory formation posit that recollection as compared to familiarity-based memory depends critically on the hippocampus, which binds features of an event to its context. For this reason, the contrast between study items that are later recollected versus those that are recognized on the basis of familiarity should reveal electrophysiological patterns in the hippocampus selectively involved in associative memory encoding. Extensive data from studies in rodents support a model in which theta oscillations fulfill this role, but results in humans results have not been as clear. Here, we employed an associative recognition memory procedure to identify hippocampal correlates of successful associative memory encoding and retrieval in patients undergoing intracranial EEG monitoring. We identified a dissociation between 2– 5 Hz and 5–9 Hz theta oscillations, by which 2–5 Hz oscillations uniquely were linked with successful associative memory in both the anterior and posterior hippocampus. These oscillations exhibited a significant phase reset that also predicted successful associative encoding, distinguished recollected from familiar items at retrieval, and contributed to reinstatement of encoding-related patterns that distinguished these items. Our results provide direct electrophysiological evidence that 2–5 Hz hippocampal theta oscillations support the encoding and retrieval of memories based on recollection but not familiarity.2.Significance StatementExtensive fMRI evidence suggests that the hippocampus plays a selective role in recollection rather than familiarity, during both encoding and retrieval. However, there is little or no electrophysiological evidence that speaks to whether the hippocampus is selectively involved in recollection. Here, we used intracranial EEG from human participants engaged in an associative recognition paradigm. The findings suggest that oscillatory power and phase reset in the hippocampus are selectively associated with recollection rather than familiarity-based memory judgements. Furthermore, reinstatement of oscillatory patterns in the hippocampus was stronger for successful recollection than familiarity. Collectively, the findings support a role for hippocampal theta oscillations in human episodic memory.

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Cognitive Processing Impacts High Frequency Intracranial EEG Activity of Human Hippocampus in Patients With Pharmacoresistant Focal Epilepsy

Frontiers in Neurology ◽

10.3389/fneur.2020.578571 ◽

2020 ◽

Vol 11 ◽

Author(s):

Jan Cimbalnik ◽

Martin Pail ◽

Petr Klimes ◽

Vojtech Travnicek ◽

Robert Roman ◽

...

Keyword(s):

Cognitive Processing ◽

High Frequency ◽

Focal Epilepsy ◽

Intracranial Eeg ◽

Eeg Activity ◽

Human Hippocampus

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Signal Complexity of Human Intracranial EEG Tracks Successful Associative-Memory Formation across Individuals

Journal of Neuroscience ◽

10.1523/jneurosci.2389-17.2017 ◽

2018 ◽

Vol 38 (7) ◽

pp. 1744-1755 ◽

Cited By ~ 21

Author(s):

Timothy C. Sheehan ◽

Vishnu Sreekumar ◽

Sara K. Inati ◽

Kareem A. Zaghloul

Keyword(s):

Associative Memory ◽

Memory Formation ◽

Intracranial Eeg ◽

Signal Complexity

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Signal complexity of human intracranial EEG tracks successful associative memory formation across individuals

10.1101/180240 ◽

2017 ◽

Cited By ~ 1

Author(s):

Timothy C. Sheehan ◽

Vishnu Sreekumar ◽

Sara K. Inati ◽

Kareem A. Zaghloul

Keyword(s):

Verbal Memory ◽

Memory Performance ◽

Memory Task ◽

Low Frequency ◽

Human Memory ◽

Memory Formation ◽

Intracranial Eeg ◽

Neural Signal ◽

Signal Complexity ◽

Successful Recall

AbstractMemory performance is highly variable between individuals. Most studies examining human memory, however, have largely focused on the neural correlates of successful memory formation within individuals, rather than the differences between them. As such, what gives rise to this variability is poorly understood. Here, we examined intracranial EEG (iEEG) recordings captured from 43 participants (23 male) implanted with subdural electrodes for seizure monitoring as they performed a paired-associates verbal memory task. We identified three separate but related signatures of neural activity that tracked differences in successful memory formation across individuals. High performing individuals consistently exhibited less broadband power, flatter power spectral density (PSD) slopes, and greater complexity in their iEEG signals. Furthermore, within individuals across three separate time scales ranging from seconds to days, successful recall was positively associated with these same metrics. Our data therefore suggest that memory ability across individuals can be indexed by increased neural signal complexity.Significance StatementWe show that participants whose intracranial EEG exhibits less low frequency power, flatter power spectrums, and greater sample entropy overall are better able to memorize associations, and that the same metrics track fluctuations in memory performance across time within individuals. These metrics together signify greater neural signal complexity which may index the brain’s ability to flexibly engage with information and generate separable memory representations. Critically, the current set of results provide a unique window into the neural markers of individual differences in memory performance which have hitherto been underexplored.

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Theta Phase Synchronization between the Human Hippocampus and Prefrontal Cortex Increases during Encoding of Unexpected Information: A Case Study

Journal of Cognitive Neuroscience ◽

10.1162/jocn_a_01302 ◽

2018 ◽

Vol 30 (11) ◽

pp. 1646-1656 ◽

Cited By ~ 13

Author(s):

Matthias J. Gruber ◽

Liang-Tien Hsieh ◽

Bernhard P. Staresina ◽

Christian E. Elger ◽

Juergen Fell ◽

...

Keyword(s):

Phase Synchronization ◽

Theta Oscillations ◽

Pharmacoresistant Epilepsy ◽

Intracranial Eeg ◽

Human Hippocampus ◽

Electrophysiological Recordings ◽

Theta Frequency ◽

Rhinal Cortex ◽

Theta Phase

Events that violate predictions are thought to not only modulate activity within the hippocampus and PFC but also enhance communication between the two regions. Scalp and intracranial EEG studies have shown that oscillations in the theta frequency band are enhanced during processing of contextually unexpected information. Some theories suggest that the hippocampus and PFC interact during processing of unexpected events, and it is possible that theta oscillations may mediate these interactions. Here, we had the rare opportunity to conduct simultaneous electrophysiological recordings from the human hippocampus and PFC from two patients undergoing presurgical evaluation for pharmacoresistant epilepsy. Recordings were conducted during a task that involved encoding of contextually expected and unexpected visual stimuli. Across both patients, hippocampal–prefrontal theta phase synchronization was significantly higher during encoding of contextually unexpected study items, relative to contextually expected study items. Furthermore, the hippocampal–prefrontal theta phase synchronization was larger for contextually unexpected items that were later remembered compared with later forgotten items. Moreover, we did not find increased theta synchronization between the PFC and rhinal cortex, suggesting that the observed effects were specific to prefrontal–hippocampal interactions. Our findings are consistent with the idea that theta oscillations orchestrate communication between the hippocampus and PFC in support of enhanced encoding of contextually deviant information.

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