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Sakon, J. J.

Publications and source records attributed to Sakon, J. J..

6 recordsLinked to original sources

Reading specific memories from human neurons before and after sleep

The ability to retrieve a single episode encountered just once is a hallmark of human intelligence and episodic memory[1]. Yet, decoding a specific memory from neuronal activity in the human brain remains a formidable challenge. Here, we develop a transformer neural network model[2, 3] trained on neuronal spikes from intracranial microelectrodes recorded during a single viewing of an audiovisual episode. Combining spikes throughout the brain via cross-channel attention[4], capable of discovering neural patterns spread across brain regions and timescales, individual participant models predict vocalization of specific concepts such as persons or places during out-of-distribution memory recall. Brain regions differentially contribute to memory decoding before and after sleep. Models trained using only medial temporal lobe (MTL) spikes significantly decode concepts before but not after sleep, while models trained using only frontal cortex (FC) spikes decode concepts after but not before sleep, with better FC decoding relating to increased non-REM sleep. These findings suggest a system-wide distribution of information across neural populations that transforms over wake/sleep cycles[5]. Such decoding of internally generated memories suggests a path towards brain-computer interfaces to treat episodic memory disorders through enhancement or muting of specific memories.

neuroscience↗

Human hippocampal ripples signal encoding of episodic memories

Recent human electrophysiology work has uncovered the presence of high frequency oscillatory events, termed ripples, during awake behavior. This prior work focuses on ripples in the medial temporal lobe (MTL) during memory retrieval. Few studies, however, investigate ripples during item encoding. Many studies have found neural activity during encoding that predicts later recall, termed subsequent memory effects (SMEs), but it is unclear if ripples during encoding also predict subsequent recall. Detecting ripples in 116 neurosurgical participants (n = 61 male) performing an episodic memory task, we find insignificant ripple SMEs in any MTL region, even as these regions exhibit robust high frequency activity (HFA) SMEs. Instead, hippocampal ripples increase during encoding of items leading to recall of temporally or semantically associated items, a phenomenon known as clustering. This subsequent clustering effect (SCE) arises specifically when hippocampal ripples occur during both encoding and retrieval, suggesting that ripples mediate the encoding and future reinstatement of episodic memories.

neuroscience↗

Hippocampal ripples signal contextually-mediated episodic recall

High-frequency oscillatory events, termed ripples, represent synchrony of neural activity in the brain. Recent evidence suggests medial temporal lobe (MTL) ripples support memory retrieval. However, it is unclear if ripples signal the reinstatement of episodic memories. Analyzing electrophysiological MTL recordings from 219 neurosurgical participants performing episodic recall tasks, we find that the rate of hippocampal ripples rises just prior to the free recall of recently-formed memories. This pre-recall ripple effect (PRE) is stronger in the CA1 and dentate gyrus (DG) subfields of hippocampus than neighboring MTL regions entorhinal and parahippocampal cortex. The PRE is also stronger prior to the retrieval of temporally and semantically clustered as compared with unclustered recalls, indicating the involvement of ripples in contextual reinstatement, which is a hallmark of episodic memory. One sentence summaryHigh frequency human hippocampal ripples occur prior to those memories most likely retrieved via episodic mechanisms.

neuroscience↗

Differences in memory for what, where, and when components of recently-formed episodes

An integral feature of human memory is the ability to recall past events. What distinguishes such episodic memory from associative and semantic memories is the joint encoding and retrieval of "what," "where," and "when" (WWW) of events. Here, we investigated whether the WWW components of episodes are retrieved with equal fidelity. Using a novel task where human participants were probed on the WWW components of a recently-viewed synthetic movie, we found fundamental differences in mnemonic accuracy between these components. The memory of "when" had the lowest accuracy and was most severely influenced by primacy and recency. Further, the memory of "when" and "where" were most susceptible to interference due to changes in memory load. These findings suggest that episodes are not stored and retrieved as a coherent whole. Rather, memory components preserve a degree of independence, suggesting that remembering coherent episodes is an active reconstruction process.

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Neural evidence of recognition--but not recall--for videos in monkey hippocampus

The role of the hippocampus in recognition memory has long been a source of debate. Tasks used to study recognition that typically require an explicit probe, where the participant must make a response to prove they remember, yield mixed results on hippocampal involvement. Here, we tasked monkeys to freely view naturalistic videos, and only tested their memory via looking times for two separate novel v. repeat video conditions on each trial. Notably, a large proportion of hippocampal neurons differentiated these videos via changes in firing rates time-locked to the duration of their presentation on screen, and not during the delay period between them as would be expected for working memory. Single neurons often contributed to both retrieval conditions, and did so across many trials with trial-unique video content, suggesting they detect familiarity. The majority of neurons contributing to the classifier showed an enhancement in firing rate on repeat compared to novel videos, a pattern which has not previously been shown in hippocampus. These results suggest the hippocampus contributes to recognition memory via familiarity during free-viewing. Significance StatementRecognition memory enables distinction of new from previously encountered stimuli. In the majority of recognition memory work, humans or animals are tasked to explicitly identify whether a stimulus is old or new. In some of these studies--but for unknown reasons not others--there is evidence of hippocampal involvement. Here, when we present trial-unique, naturalistic videos to monkeys, firing rates from many single hippocampal neurons surprisingly differentiate new from repeated videos. The ability of these hippocampal neurons to detect recently-viewed stimuli, despite the videos unfamiliar content, suggests they contribute to memory. These results are consistent with hippocampal involvement in the familiarity aspect of recognition memory during free-viewing.

neuroscience↗

Population coding of pattern separation in the monkey hippocampus

The CA3 and dentate gyrus (DG) regions of the hippocampus are considered key for disambiguating sensory inputs from similar experiences in memory, a process termed pattern separation. The neural mechanisms underlying pattern separation, however, have been difficult to compare across species: rodents offer robust recording methods with less human-centric tasks while humans provide complex behavior with less recording potential. To overcome these limitations, we trained monkeys to perform a visual pattern separation task similar to those used in humans while recording activity from single CA3/DG neurons. We find that when animals discriminate recently seen novel images from similar (lure) images, behavior indicative of pattern separation, CA3/DG neurons respond to lure images more like novel than repeat images. Using a population of these neurons, we are able to classify novel, lure, and repeat images from each other using this pattern of firing rates. Notably, one subpopulation of these neurons is more responsible for distinguishing lures and repeats--the key discrimination indicative of pattern separation.

neuroscience↗