Bernhard P. Staresina

Oscillations and Episodic Memory: Addressing the Synchronization/Desynchronization Conundrum.

Brain oscillations are one of the core mechanisms underlying episodic memory. However, while some studies highlight the role of synchronized oscillatory activity, others highlight the role of desynchronized activity. We here describe a framework to resolve this conundrum and integrate these two opposing oscillatory behaviors. Specifically, we argue that the synchronization and desynchronization reflect a division of labor between a hippocampal and a neocortical system, respectively. We describe a novel oscillatory framework that integrates synchronization and desynchronization mechanisms to explain how the two systems interact in the service of episodic memory.

Hippocampal pattern completion is linked to gamma power increases and alpha power decreases during recollection

How do we retrieve vivid memories upon encountering a simple cue? Computational models suggest that this feat is accomplished by pattern completion processes involving the hippocampus. However, empirical evidence for hippocampal pattern completion and its underlying mechanisms has remained elusive. Here, we recorded direct intracranial EEG as human participants performed an associative memory task. For each study (encoding) and test (retrieval) event, we derived time-frequency resolved representational patterns in the hippocampus and compared the extent of pattern reinstatement for different mnemonic outcomes. Results show that successful associative recognition (AR) yields enhanced event-specific reinstatement of encoding patterns compared to non-associative item recognition (IR). Moreover, we found that gamma power (50–90 Hz) increases – in conjunction with alpha power (8–12 Hz) decreases not only distinguish AR from IR, but also correlate with the level of hippocampal reinstatement. These results link single-shot hippocampal pattern completion to episodic recollection and reveal how oscillatory dynamics in the gamma and alpha bands orchestrate these mnemonic processes. DOI: http://dx.doi.org/10.7554/eLife.17397.001

Gamma Power Reductions Accompany Stimulus-Specific Representations of Dynamic Events

Neural representations of specific stimuli rely on activity patterns in distributed neural assemblies [1-4]. According to one influential view, these assemblies are characterized by synchronized gamma-band activity (GBA) [5-11] that reflects stimulus-specific representations [12-14]. However, recent studies have shown that GBA is closely correlated with the overall amount of cellular activity and may be detrimental for precise representations of specific stimuli [15, 16]. Until now, the role of GBA for the formation of dynamically changing representations has been unknown. Here, we applied representational similarity analysis (RSA) [17] to intracranial electroencephalogram (iEEG) data from ten presurgical epilepsy patients to identify stimulus-specific neural representations. Patients first learned and then retrieved their paths through virtual houses. Dynamic representations were identified by the rapidly changing distributions of frequency-specific global (spatial) activity patterns across the brain. We found that GBA patterns during successful (but not unsuccessful) retrieval of one sequence were more similar to activity during encoding of that same sequence compared to other sequences. The contribution of individual electrodes to these global representations was correlated with local similarity in individual electrodes (i.e., with RSA across time). Moreover, time-resolved RSA values were negatively correlated with the magnitude of iEEG gamma power: RSA values were higher at time points when gamma power was reduced. Both global and local representations relied on a small proportion of electrodes. These results show that behaviorally relevant neural representations of specific dynamically changing stimuli can be tracked by iEEG recordings and that they are associated with reductions of gamma power.

Memory Consolidation Is Linked to Spindle-Mediated Information Processing during Sleep

Summary How are brief encounters transformed into lasting memories? Previous research has established the role of non-rapid eye movement (NREM) sleep, along with its electrophysiological signatures of slow oscillations (SOs) and spindles, for memory consolidation [1, 2, 3, 4]. In related work, experimental manipulations have demonstrated that NREM sleep provides a window of opportunity to selectively strengthen particular memory traces via the delivery of auditory cues [5, 6, 7, 8, 9, 10], a procedure known as targeted memory reactivation (TMR). It has remained unclear, however, whether TMR triggers the brain’s endogenous consolidation mechanisms (linked to SOs and/or spindles) and whether those mechanisms in turn mediate effective processing of mnemonic information. We devised a novel paradigm in which associative memories (adjective-object and adjective-scene pairs) were selectively cued during a post-learning nap, successfully stabilizing next-day retention relative to non-cued memories. First, we found that, compared to novel control adjectives, memory cues evoked an increase in fast spindles. Critically, during the time window of cue-induced spindle activity, the memory category linked to the verbal cue (object or scene) could be reliably decoded, with the fidelity of this decoding predicting the behavioral consolidation benefits of TMR. These results provide correlative evidence for an information processing role of sleep spindles in service of memory consolidation.

Theta Phase Synchronization Between The Human Hippocampus And The Prefrontal Cortex Supports Learning Of Unexpected Information

Events that violate predictions are thought to not only modulate activity within the hippocampus and prefrontal cortex, but also to enhance communication between the two regions. Several studies in rodents have shown that synchronized theta oscillations facilitate communication between the prefrontal cortex and hippocampus during salient events, but it remains unclear whether similar oscillatory mechanisms support interactions between the two regions in humans. Here, we had the rare opportunity to conduct simultaneous electrophysiological recordings from the human hippocampus and prefrontal cortex from two patients undergoing presurgical evaluation for pharmaco-resistant 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 unexpected study items, compared to contextually expected study items. In contrast, we did not find increased theta synchronization between the prefrontal cortex and rhinal cortex. Our findings are consistent with the idea that theta oscillations orchestrate communication between the hippocampus and prefrontal cortex during the processing of contextually salient information.

Neuronal Oscillations and Reactivation Subserving Memory Consolidation

Newly acquired memories are initially hippocampus-dependent and need to undergo a process of active system consolidation, during which they are redistributed to neocortical sites for long-term storage. This process is thought to take place during phases of quiet wakefulness and non-rapid-eye movement (NREM) sleep and is presumably based on the repeated reactivation of memory engrams (patterns of hippocampo-neocortical connections) which gradually drives the establishment of respective direct cortico-cortical connections. During NREM sleep (and similarly during quiet wakefulness), control via brainstem neuromodulatory systems (in particular the cholinergic one) enables a specific kind of oscillatory activity in the thalamo-neocortico-hippocampal system that facilitates memory reactivation. NREM oscillatory activity is characterized by the neocortical slow oscillation (SO; 80 Hz). The intricate interaction of SOs, spindles and ripples constitutes a set of hierarchically nested oscillations, which provides the fine-tuned temporal and spatial structure that is required to orchestrate the reactivation of memory traces and the information flow between hippocampus and neocortex. In this chapter we (i) provide a conceptual introduction to system memory consolidation, (ii) describe the neuronal mechanisms thought to underlie the generation of and interaction between SOs, spindles and ripples, (iii) discuss how these oscillations presumably mediate memory reactivation and hippocampo-neocortical cross-talk, and (iv) outline new promising approaches to directly study the ongoing reactivation of memory representations in humans.

Memory encoding-related anterior hippocampal potentials are modulated by deep brain stimulation of the entorhinal area

Deep brain stimulation (DBS) of the human entorhinal area using 50 Hz pulses has revealed conflicting results regarding memory performance. Moreover, its impact on memory‐related hippocampal potentials has not yet been investigated.

Speed of time-compressed forward replay flexibly changes in human episodic memory

Remembering information from continuous past episodes is a complex task. On the one hand, we must be able to recall events in a highly accurate way that often includes exact timing; on the other hand, we can ignore irrelevant details and skip to events of interest. We here track continuous episodes, consisting of different sub-events, as they are recalled from memory. In behavioral and MEG data, we show that memory replay is temporally compressed and proceeds in a forward direction. Neural replay is characterized by the reinstatement of temporal patterns from encoding. These fragments of activity reappear on a compressed timescale. Herein, the replay of sub-events takes longer than the transition from one sub-event to another. This identifies episodic memory replay as a dynamic process in which participants replay fragments of fine-grained temporal patterns and are able to skip flexibly across sub-events.

Hippocampal synchrony and neocortical desynchrony cooperate to encode and retrieve episodic memories

Episodic memories hinge upon our ability to process a wide range of multisensory information and bind this information into a coherent, memorable representation. On a neural level, these two processes are thought to be supported by neocortical alpha/beta desynchronisation and hippocampal theta/gamma synchronisation, respectively. Intuitively, these two processes should interact to successfully build and retrieve episodic memories, yet this hypothesis has not been tested empirically. Here, we address this question by analysing human intracranial EEG data recorded during an associative memory task that involved the pairing of life-like, dynamic stimuli to verbal stimuli. Our findings indicate that neocortical alpha/beta (8-20Hz) desynchronisation reliably precedes and predicts hippocampal 9fast9 gamma (60-80Hz) synchronisation during episodic memory formation; during episodic memory retrieval however, hippocampal 9slow9 gamma (40-50Hz) synchronisation reliably precedes and predicts later neocortical alpha/beta desynchronisation. We speculate that this cooperation reflects the flow of information from neocortex to hippocampus during memory formation, and hippocampal pattern completion inducing information reinstatement in the neocortex during memory retrieval.Episodic memories hinge upon our ability to process a wide range of multisensory information and bind this information into a coherent, memorable representation. On a neural level, these two processes are thought to be supported by neocortical alpha/beta desynchronisation and hippocampal theta/gamma synchronisation, respectively. Intuitively, these two processes should couple to successfully create and retrieve episodic memories, yet this hypothesis has not been tested empirically. We address this by analysing human intracranial EEG data recorded during two associative memory tasks. We find that neocortical alpha/beta (8-20Hz) power decreases reliably precede and predict hippocampal “fast” gamma (60-80Hz) power increases during episodic memory formation; during episodic memory retrieval however, hippocampal “slow” gamma (40-50Hz) power increases reliably precede and predict later neocortical alpha/beta power decreases. We speculate that this coupling reflects the flow of information from neocortex to hippocampus during memory formation, and hippocampal pattern completion inducing information reinstatement in the neocortex during memory retrieval. Significance Statement Episodic memories detail our personally-experienced past. The formation and retrieval of these memories has long been thought to be supported by a division of labour between the neocortex and the hippocampus, where the former processes event-related information and the latter binds this information together. However, it remains unclear how the two regions interact. We uncover directional coupling between these regions, with power decreases in the neocortex that precede and predict power increases in the hippocampus during memory formation. Fascinatingly, this process reverses during memory retrieval, with hippocampal power increases preceding and predicting neocortical power decreases. These results suggest a bidirectional flow of information between the neocortex and hippocampus is fundamental to the formation and retrieval of episodic memories.

Sleep Spindles and Memory Reprocessing

We propose a framework for the memory function of spindle oscillations during sleep. In this framework, memories are reinstated by spindle events and further reprocessed during subsequent spindle refractory periods. We posit that spindle refractoriness is crucial for protecting memory reprocessing from interference. We further argue that temporally-coordinated spindle refractory periods across local networks facilitate the consolidation of rich, multimodal representations, and that localized spindle refractoriness optimizes oscillatory interactions that support systems consolidation in the sleeping brain.