Episodic memory retrieval relies on the recovery of neural representations of waking experience. This process is thought to involve a communication dynamic between the medial temporal lobe memory ...system and the neocortex. How this occurs is largely unknown, however, especially as it pertains to awake human memory retrieval. Using intracranial electroencephalographic recordings, we found that ripple oscillations were dynamically coupled between the human medial temporal lobe (MTL) and temporal association cortex. Coupled ripples were more pronounced during successful verbal memory retrieval and recover the cortical neural representations of remembered items. Together, these data provide direct evidence that coupled ripples between the MTL and association cortex may underlie successful memory retrieval in the human brain.
Episodic memory retrieval is thought to rely on the replay of past experiences, yet it remains unknown how human single-unit activity is temporally organized during episodic memory encoding and ...retrieval. We found that ripple oscillations in the human cortex reflect underlying bursts of single-unit spiking activity that are organized into memory-specific sequences. Spiking sequences occurred repeatedly during memory formation and were replayed during successful memory retrieval, and this replay was associated with ripples in the medial temporal lobe. Together, these data demonstrate that human episodic memory is encoded by specific sequences of neural activity and that memory recall involves reinstating this temporal order of activity.
Significance Our results represent significant contributions to understanding the neural mechanisms and spatiotemporal dynamics governing neural reinstatement in two important ways. First, by using a ...cued recall memory task, our paradigm offers experimental control over retrieval. We compare reinstatement during correct and incorrect retrieval, and provide evidence that retrieval recovers a gradually changing representation of temporal context. These data provide support for mental time travel hypothesized to underlie episodic memory. Second, leveraging the high temporal precision afforded by intracranial recordings, we investigate the precise timing of reinstatement and demonstrate that retrieval may reactivate cortical representations of a memory on a faster timescale than during encoding. Our data complement previous studies demonstrating faster replay of patterns associated with a prior episode.
Reinstatement of neural activity is hypothesized to underlie our ability to mentally travel back in time to recover the context of a previous experience. We used intracranial recordings to directly examine the precise spatiotemporal extent of neural reinstatement as 32 participants with electrodes placed for seizure monitoring performed a paired-associates episodic verbal memory task. By cueing recall, we were able to compare reinstatement during correct and incorrect trials, and found that successful retrieval occurs with reinstatement of a gradually changing neural signal present during encoding. We examined reinstatement in individual frequency bands and individual electrodes and found that neural reinstatement was largely mediated by temporal lobe theta and high-gamma frequencies. Leveraging the high temporal precision afforded by intracranial recordings, our data demonstrate that high-gamma activity associated with reinstatement preceded theta activity during encoding, but during retrieval this difference in timing between frequency bands was absent. Our results build upon previous studies to provide direct evidence that successful retrieval involves the reinstatement of a temporal context, and that such reinstatement occurs with precise spatiotemporal dynamics.
This scientific commentary refers to ‘Thalamostriatal disconnection underpins long-term seizure freedom in frontal lobe epilepsy surgery’ by Giampiccolo et al. (https://doi.org/10.1093/brain/awad085).
Memory performance is highly variable among individuals. Most studies examining human memory, however, have largely focused on the neural correlates of successful memory formation within individuals, ...rather than the differences among 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 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.
We 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 provides a unique window into the neural markers of individual differences in memory performance, which have hitherto been underexplored.
Objectives
Neuroinflammation, implicated in epilepsy, can be imaged in humans with positron emission tomography (PET) ligands for translocator protein 18 kDa (TSPO). Previous studies in patients with ...temporal lobe epilepsy and mesial temporal sclerosis found increased 11CPBR28 uptake ipsilateral to seizure foci. Neocortical foci present more difficult localization problems and more variable underlying pathology.
Methods
We studied 11 patients with neocortical seizure foci using 11CPBR28 or 11C N,N‐diethyl‐2‐(4‐methoxyphenyl)‐5,7‐dimethylpyrazolo1,5‐apyrimidine‐3‐acetamide (DPA) 713, and 31 healthy volunteers. Seizure foci were identified with structural magnetic resonance imaging (MRI) and ictal video–electroencephalography (EEG) monitoring. Six patients had surgical resections; five had focal cortical dysplasia type 2A or B and one microdysgenesis. Brain regions were delineated using FreeSurfer and T1‐weighted MRI. We measured brain radioligand uptake (standardized uptake values SUVs) in ipsilateral and contralateral regions, to compare calculated asymmetry indices AIs; 200% *(ipsilateral − contralateral)/(ipsilateral + contralateral) between epilepsy patients and controls, as well as absolute 11CPBR28 binding as the ratio of distribution volume to free fraction (VT/fP) in 9 patients (5 high affinity and 4 medium affinity binders) and 11 age‐matched volunteers (5 high‐affinity and 6 medium affinity) who had metabolite‐corrected arterial input functions measured.
Results
Nine of 11 patients had AIs exceeding control mean 95% confidence intervals in at least one region consistent with the seizure focus. Three of the nine had normal MRI. There was a nonsignificant trend for patients to have higher binding than volunteers both ipsilateral and contralateral to the focus in the group that had absolute binding measured.
Significance
Our study demonstrates the presence of focal and distributed inflammation in neocortical epilepsy. There may be a role for TSPO PET for evaluation of patients with suspected neocortical seizure foci, particularly when other imaging modalities are unrevealing. However, a complex method, inherent variability, and increased binding in regions outside seizure foci will limit applicability.
Sequences of spiking activity have been heavily implicated as potential substrates of memory formation and retrieval across many species. A parallel line of recent evidence also asserts that ...sequential activity may arise from and be constrained by pre-existing network structure. Here we reconcile these two lines of research in the human brain by measuring single unit spiking sequences in the temporal lobe cortex as participants perform an episodic memory task. We find the presence of an average backbone spiking sequence identified during pre-task rest that is stable over time and different cognitive states. We further demonstrate that these backbone sequences are composed of both rigid and flexible sequence elements, and that flexible elements within these sequences serve to promote memory specificity when forming and retrieving new memories. These results support the hypothesis that pre-existing network dynamics serve as a scaffold for ongoing neural activity in the human cortex.
Our memories enable us to form expectations for our future experiences, yet the precise neural mechanisms underlying how we compare any experience to our memory remain unknown. Here, using ...intracranial EEG recordings, we show that episodic memories formed after a single visual experience establish expectations for future experience within neocortical-medial temporal lobe circuits. When subsequent experiences violate these expectations, we find a 80-120 Hz prediction error signal that emerges in both visual association areas and the medial temporal lobe. Critically, this error signal emerges in visual association areas first and then propagates to the medial temporal lobe. This error signal is accompanied by alpha coherence between the two regions. Our data therefore suggest that internal models formed from episodic memories are generated throughout the visual hierarchy after just a single exposure, and that these internal models are then used for comparison with future experiences.
IMPORTANCE: Neuroinflammation may play a role in epilepsy. Translocator protein 18 kDa (TSPO), a biomarker of neuroinflammation, is overexpressed on activated microglia and reactive astrocytes. A ...preliminary positron emission tomographic (PET) imaging study using carbon 11 (11C)–labeled PBR28 in patients with temporal lobe epilepsy (TLE) found increased TSPO ipsilateral to seizure foci. Full quantitation of TSPO in vivo is needed to detect widespread inflammation in the epileptic brain. OBJECTIVES: To determine whether patients with TLE have widespread TSPO overexpression using 11CPBR28 PET imaging, and to replicate relative ipsilateral TSPO increases in patients with TLE using 11CPBR28 and another TSPO radioligand, 11CDPA-713. DESIGN, SETTING, AND PARTICIPANTS: In a cohort study from March 2009 through September 2013 at the Clinical Epilepsy Section of the National Institute of Neurological Disorders and Stroke, participants underwent brain PET and a subset had concurrent arterial sampling. Twenty-three patients with TLE and 11 age-matched controls were scanned with 11CPBR28, and 8 patients and 7 controls were scanned with 11CDPA-713. Patients with TLE had unilateral temporal seizure foci based on ictal electroencephalography and structural magnetic resonance imaging. Participants with homozygous low-affinity TSPO binding were excluded. MAIN OUTCOMES AND MEASURES: The 11CPBR28 distribution volume (VT) corrected for free fraction (fP) was measured in patients with TLE and controls using FreeSurfer software and T1-weighted magnetic resonance imaging for anatomical localization of bilateral temporal and extratemporal regions. Side-to-side asymmetry in patients with TLE was calculated as the ratio of ipsilateral to contralateral 11CPBR28 and 11CDPA-713 standardized uptake values from temporal regions. RESULTS: The 11CPBR28 VT to fp ratio was higher in patients with TLE than in controls for all ipsilateral temporal regions (27%-42%; P < .05) and in contralateral hippocampus, amygdala, and temporal pole (approximately 30%-32%; P < .05). Individually, 12 patients, 10 with mesial temporal sclerosis, had asymmetrically increased hippocampal 11CPBR28 uptake exceeding the 95% confidence interval of the controls. Binding of 11CPBR28 was increased significantly in thalamus. Relative 11CPBR28 and 11CDPA-713 uptakes were higher ipsilateral than contralateral to seizure foci in patients with TLE (11CPBR28: 2%-6%; 11CDPA-713: 4%-9%). Asymmetry of 11CDPA-713 was greater than that of 11CPBR28 (F = 29.4; P = .001). CONCLUSIONS AND RELEVANCE: Binding of TSPO is increased both ipsilateral and contralateral to seizure foci in patients with TLE, suggesting ongoing inflammation. Anti-inflammatory therapy may play a role in treating drug-resistant epilepsy.
Recent evidence has suggested that coherent neuronal oscillations may serve as a gating mechanism for flexibly modulating communication between brain regions. For this to occur, such oscillations ...should be robust and coherent between brain regions that also demonstrate time-locked correlations, with time delays that match the phase delays of the coherent oscillations. Here, by analyzing functional connectivity in both the time and frequency domains, we demonstrate that alpha oscillations satisfy these constraints and are well suited for modulating communication over large spatial scales in the human brain. We examine intracranial EEG in the human temporal lobe and find robust alpha oscillations that are coherent between brain regions with center frequencies that are consistent within each individual participant. Regions demonstrating coherent narrowband oscillations also exhibit time-locked broadband correlations with a consistent time delay, a requirement for an efficient communication channel. The phase delays of the coherent alpha oscillations match the time delays of the correlated components, and importantly, both broadband correlations and neuronal spiking activity are modulated by the phase of the oscillations. These results are specific to the alpha band and build upon emerging evidence suggesting that alpha oscillations may play an active role in cortical function. Our data therefore provide evidence that large-scale communication in the human brain may be rhythmically modulated by alpha oscillations.
•Analysis of human electrophysiology at multiple spatial scales•Pairs of regions with correlated broadband activity are also alpha coherent•The phase delays of the oscillations match the time delays of broadband activity•Large-scale correlations and spiking activity are modulated by the phase of alpha
Chapeton et al. show that alpha oscillations in the human cortex satisfy several constraints that are necessary for using oscillatory coherence as a means of modulating large-scale cortical communication. The results are specific to the alpha band and supported by single-unit spiking activity.
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