Maria Wimber

Stereo-electroencephalography (SEEG) involves the implantation of depth electrodes in the brain to monitor epileptic seizures for surgical feasibility. As the electrodes advance into deeper limbic structures, the macro contacts distributed along the shaft record electrical activity from more lateral sites, while a bundled array of microwires simultaneously captures highly localised signals from the tip of the electrode. In a clinical setting these electrical signals are recorded relative to a reference signal, which may be sub-optimal for subsequent analyses that are unrelated to clinical objectives. Therefore, a secondary re-referencing operation is often undertaken to transform the signal in relation to a specific hypothesis. Despite a recent surge in SEEG studies, comparative studies on the much-understudied issue of re-referencing are sparse. Here, we analyse data collected from 16 human patients during an episodic memory task and comparatively apply a range of re-referencing methods to both macro contact and micro-wire data. We find that the choice of method changes the proportion of trials that survive artefact rejection, low frequency power, and the aperiodic background against which that power is read. In the hippocampal recordings, however, no method differed from any other in the size of a memory effect in power or spike–field coherence. This early transformative decision therefore bears on how the signal is described. We found no evidence that it changes the detectability of the behavioural effects tested here, and no method reversed the direction of a memory effect.

Schemas, knowledge structures that represent regularities across episodes, can enhance memory for events that are either congruent or incongruent with their content. Across four experiments including 193 university students, we investigated whether these schema effects emerge when chronology forms a core aspect of a schema’s content, enabling temporal predictions of future events. After pre-training on schematically defined four-item sequences, participants studied novel sequences that either affirmed, violated, or were unrelated to these schemas. Memory benefits were observed for both schematically congruent and incongruent sequences relative to sequences that were schema-unrelated. Critically, incongruent memory benefits only emerged for violations of content, and not for violations of temporal order, despite behavioural evidence of prediction error at encoding for both violation types. Our findings show that schema effects depend on the type of schematic violation and that incongruent benefits are not the inevitable consequence of prediction error at encoding.

Direct electrical stimulation (DES) can advance our understanding of the intricate dynamics of the human hippocampo-neocortical network, which underlies complex cognitive processes such as spatial cognition and memory. This knowledge can help Neurotechnology to more effectively interface with this network and improve its functions. Here, we investigated the effects of DES in seven epilepsy patients under medical supervision recording single neuron activity alongside local field potentials to investigate neural responses to single pulses at different levels of granularity. Our results demonstrate that (i) single neurons respond to local electrical stimulation with a stereotypical pattern of short-lived increased excitation, followed by sustained inhibition, (ii) that input into the hippocampus from neocortex takes ∼100 ms, and (iii) that output from the hippocampus to the neocortex is gated by theta phase. These results are vital to inform the optimal choice of parameters for future electrical stimulation studies targeting the human memory system.

How the human brain reconstructs, step-by-step, the core elements of past experiences is still unclear. Here, we map the spatiotemporal trajectories along which visual object memories are reconstructed during associative recall. Specifically, we inquire whether retrieval reinstates feature representations in a copy-like but reversed direction with respect to the initial perceptual experience, or alternatively, this reconstruction involves format transformations and regions beyond initial perception. Participants from two cohorts studied new associations between verbs and randomly paired object images, and subsequently recalled the objects when presented with the corresponding verb cue. We first analyze multivariate fMRI patterns to map where in the brain high- and low-level object features can be decoded during perception and retrieval, showing that retrieval is dominated by conceptual features, represented in comparatively late visual and parietal areas. A separately acquired EEG dataset is then used to track the temporal evolution of the reactivated patterns using similarity-based EEG–fMRI fusion. This fusion suggests that memory reconstruction proceeds from anterior frontotemporal to posterior occipital and parietal regions, in line with a conceptual-to-perceptual gradient but only partly following the same trajectories as during perception. Specifically, a linear regression statistically confirms that the sequential activation of ventral visual stream regions is reversed between image perception and retrieval. The fusion analysis also suggests an information relay to frontoparietal areas late during retrieval. Together, the results shed light onto the temporal dynamics of memory recall and the transformations that the information undergoes between the initial experience and its later reconstruction from memory.

The application of multivariate pattern analysis (MVPA) to electroencephalography (EEG) data allows neuroscientists to track neural representations at temporally fine-grained scales. This approach has been leveraged to study the locus and evolution of long-term memory contents in the brain, but a limiting factor is that decoding performance remains low. A key reason for this is that processes like encoding and retrieval are intrinsically dynamic across trials and participants, and this runs in tension with MVPA and other techniques that rely on consistently unfolding neural codes to generate predictions about memory contents. The presentation of visually perturbing stimuli may experimentally regularize brain dynamics, making neural codes more stable across measurements to enhance representational readouts. Such enhancements, which have repeatedly been demonstrated in working memory contexts, remain to our knowledge unexplored in long-term memory tasks. In this study, we evaluated whether visual perturbations—or pings —improve our ability to predict the category of retrieved images from EEG activity during cued recall. Overall, our findings suggest that while pings evoked a prominent neural response, they did not reliably produce improvements in MVPA-based classification across several analyses. We discuss possibilities that could explain these results, including the role of experimental and analysis parameter choices and mechanistic differences between working and long-term memory.

The hippocampus is an essential hub for episodic memory processing. However, how human hippocampal single neurons code multi-element associations remains unknown. In particular, it is debated whether each hippocampal neuron represents an invariant element within an episode or whether single neurons bind together all the elements of a discrete episodic memory. Here we provide evidence for the latter hypothesis. Using single-neuron recordings from a total of 30 participants, we show that individual neurons, which we term episode-specific neurons, code discrete episodic memories using either a rate code or a temporal firing code. These neurons were observed exclusively in the hippocampus. Importantly, these episode-specific neurons do not reflect the coding of a particular element in the episode (that is, concept or time). Instead, they code for the conjunction of the different elements that make up the episode.

Remembering facilitates future remembering. This benefit of practicing by active retrieval, as compared to more passive relearning, is known as the testing effect and is one of the most robust findings in the memory literature. It has typically been assessed using verbal materials such as word pairs, sentences, or educational texts. We here investigate if memory for visual materials equally benefits from retrieval-mediated learning. Based on cognitive and neuroscientific theories, we hypothesize that testing effects will be limited to meaningful visual images that can be related to preexisting knowledge. In a series of four experiments, we systematically varied the type of material (meaningless "squiggle" shapes vs. meaningful object images) and the format of the test used to probe memory (a visually driven alternative forced-choice test vs. a remember/know recognition test). Within each experiment, we assessed the effects of practice type (retrieval or restudy) and the delay of the final test (immediate vs. 1 week) on the resulting practice benefits. Abstract shapes never showed a significant testing benefit, irrespective of test format. Meaningful object images did benefit from testing, particularly at long delays, and with a test format probing the recollective component of recognition memory. Together, our results indicate that retrieval can facilitate the recollection of visual images when they represent meaningful semantic units. This pattern of results is predicted by cognitive and neurobiologically motivated theories proposing that retrieval's benefits emerge through spreading activation in semantic networks, producing more easily accessible and longer-lasting memory traces. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Our understanding of how information unfolds when we recall events from memory remains limited. In this study, we investigate whether the reconstruction of visual object memories follows a backward trajectory along the ventral visual stream with respect to perception, such that their neural feature representations are gradually reinstated from late areas close to the hippocampus backwards to lower-level sensory areas. We use multivariate analyses of fMRI activation patterns to map the constituent features of the object memories onto the brain during retrieval, and EEG-fMRI fusion to track the temporal evolution of the reactivated patterns. Participants studied new associations between verbs and randomly paired object images in an encoding phase, and subsequently recalled the objects when presented with the corresponding verb cue. Decoding reactivated memory features from fMRI activity revealed that retrieval patterns were dominated by conceptual features, represented in comparatively late visual and parietal areas. Representational-similarity-based fusion then allowed us to map the EEG patterns that emerged at each given time point of a trial onto the spatially resolved fMRI patterns. This fusion suggests that memory reconstruction proceeds backwards along the ventral visual stream from anterior fronto-temporal to posterior occipital and parietal regions, in line with a semantic-to-perceptual gradient. A linear regression on the peak time points of reactivated brain regions statistically confirms that the temporal progression is reversed with respect to encoding. Together, the results shed light onto the spatio-temporal trajectories along which memories are reconstructed during associative retrieval, and which features of an image are reconstructed when in time and where in the brain.

Theta and gamma oscillations in the medial temporal lobe are suggested to play a critical role for human memory formation via establishing synchrony in neural assemblies. Arguably, such synchrony facilitates efficient information transfer between neurons and enhances synaptic plasticity, both of which benefit episodic memory formation. However, to date little evidence exists from humans that would provide direct evidence for such a specific role of theta and gamma oscillations for episodic memory formation. Here, we investigate how oscillations shape the temporal structure of neural firing during memory formation in the medial temporal lobe. We measured neural firing and local field potentials in human epilepsy patients via micro-wire electrode recordings to analyze whether brain oscillations are related to co-incidences of firing between neurons during successful and unsuccessful encoding of episodic memories. The results show that phase-coupling of neurons to faster theta and gamma oscillations correlates with co-firing at short latencies (~20–30 ms) and occurs during successful memory formation. Phase-coupling at slower oscillations in these same frequency bands, in contrast, correlates with longer co-firing latencies and occurs during memory failure. Thus, our findings suggest that neural oscillations play a role for the synchronization of neural firing in the medial temporal lobe during the encoding of episodic memories.

Competition between overlapping memories is considered one of the major causes of forgetting, and it is still unknown how the human brain resolves such mnemonic conflict. In the present magnetoencephalography (MEG) study, we empirically tested a computational model that leverages an oscillating inhibition algorithm to minimise overlap between memories. We used a proactive interference task, where a reminder word could be associated with either a single image (non-competitive condition) or two competing images, and participants were asked to always recall the most recently learned word–image association. Time-resolved pattern classifiers were trained to detect the reactivated content of target and competitor memories from MEG sensor patterns, and the timing of these neural reactivations was analysed relative to the phase of the dominant hippocampal 3 Hz theta oscillation. In line with our pre-registered hypotheses, target and competitor reactivations locked to different phases of the hippocampal theta rhythm after several repeated recalls. Participants who behaviourally experienced lower levels of interference also showed larger phase separation between the two overlapping memories. The findings provide evidence that the temporal segregation of memories, orchestrated by slow oscillations, plays a functional role in resolving mnemonic competition by separating and prioritising relevant memories under conditions of high interference.