Biology subjects

Bein, O.

Publications and source records attributed to Bein, O..

5 recordsLinked to original sources

bioRxiv2023

Evidence for impaired hippocampal circuitry in schizophrenia and its link to memory dysfunction

Pattern separation and pattern completion are opposing yet complementary components of mnemonic processing that heavily rely on the hippocampus. It has been shown that processing within the dentate gyrus (DG) subfield promotes pattern separation while operations within the CA3 subfield are important for pattern completion. Schizophrenia has been associated with anatomical and functional hippocampal abnormalities, including within the DG and CA3. We hypothesized that an impairment in hippocampal circuitry in individuals with first-episode schizophrenia leads to deficits in pattern separation (mnemonic discrimination) and pattern completion (recognition memory), that these deficits contribute to delusions, and that antipsychotic treatment improves circuit functioning. We measured behavioral and neural responses during the identification of new, repeated, and similar stimuli using high-resolution fMRI in 45 medication-free or minimally-treated patients with first-episode schizophrenia and 49 matched controls. We found recognition memory and pattern separation deficits in patients and a negative association between memory performance and the severity of delusions. Neural analyses revealed deficits in both univariate BOLD responses and multivariate patterns in the hippocampus during mnemonic discrimination in patients compared to controls. Importantly, by investigating the association between trial-level neural activity and behavior before and after treatment, we found that antipsychotics normalized DG activity during pattern separation and CA3 activity during pattern completion. Lastly, trial-level cortical responses during mnemonic discrimination predicted performance in patients at baseline, suggesting a compensatory role. This study provides new insight into the impact of schizophrenia and antipsychotic treatment on memory systems and uncovers systems-level contributions to pattern separation and pattern completion.

neuroscience↗

bioRxiv2022

Event integration and temporal pattern separation: how hierarchical knowledge emerges in hippocampal subfields through learning

Everyday life is composed of events organized by changes in contexts, with each event containing an unfolding sequence of occurrences. A major challenge facing our memory systems is how to integrate sequential occurrences within events while also maintaining their details and avoiding over-integration across different contexts. Here we asked if and how distinct hippocampal subfields come to hierarchically, and in parallel, represent both event context and subevent occurrences with learning. Participants viewed sequential events defined as sequences of objects superimposed on shared color frames while undergoing high-resolution fMRI. Importantly, these events were repeated to induce learning. Event segmentation, as indexed by increased reaction times at event boundaries, was observed in all repetitions. Temporal memory decisions were quicker for items from the same event compared to across different events, indicating that events shaped memory behavior. With learning, hippocampal CA3 multivoxel activation patterns clustered to reflect the event context, with more clustering correlated with behavioral facilitation during event transitions. In contrast, in the dentate gyrus temporally proximal items that belonged to the same event became associated with more differentiated neural patterns. A computational model explained these results by dynamic inhibition in the dentate gyrus. Additional similarity measures support the notion that CA3 clustered representations reflect shared voxel populations, while dentate gyrus distinct item representations reflect different voxel populations. These findings suggest an interplay between temporal differentiation in dentate gyrus and attractor dynamics in CA3. They advance our understanding of how knowledge is structured through integration and separation across time and context. SignificanceA major challenge of our memory system is to integrate experiences occurring in the same context to generalize context-appropriate knowledge, while also maintaining distinct representations of these same occurrences to avoid confusion. Here, we uncover a novel mechanism for hierarchical learning in the human hippocampus that might help to resolve this tension. In the CA3 subregion of the hippocampus, the neural representations of items presented sequentially in the same context, but not in different contexts, became more overlapping with learning. In contrast, adjacent items, appearing close in time and in the same context, became increasingly more differentiated in the dentate gyrus. Thus, multiple representations in different hippocampal subregions encoded in parallel might enable simultaneous generalization and specificity in memory.

neuroscience↗

bioRxiv2019

The direction of associations: prior knowledge promotes hippocampal separation, but cortical assimilation

What does it mean to say, "a new association is learned"? And how is this learning different when adding new information to already-existing knowledge? Here, participants associated pairs of faces while undergoing fMRI, under two different conditions: a famous, highly-familiar face with a novel face or two novel faces. We examined multivoxel activity patterns corresponding to individual faces before and after learning. In the hippocampus, paired novel faces became more similar to one another through learning. In striking contrast, members of famous-novel pairs became distinct. In the cortex, prior knowledge led to integration, but in a specific direction: the representation of the novel face became similar to that of the famous face before learning, but less so vice versa, suggesting assimilation of new into old memories. We propose that hippocampal separation might resolve interference between existing and newly learned information, allowing cortical assimilation. Associations are formed through divergent but specific neural codes, that are adaptively shaped by the internal state of the system - its prior knowledge.

neuroscience↗

bioRxiv2019

Face Selective Neural Activity: comparison between fixed and free viewing

Event Related Potentials (ERPs) are widely used to study category-selective EEG responses to visual stimuli, such as the face-selective N170 component. Typically, this is done by flashing stimuli abruptly at the point of static gaze fixation. While allowing for good experimental control, these paradigms ignore the dynamic role of eye-movements in natural vision. Fixation-related potentials (FRPs) obtained using simultaneous EEG and eye-tracking, overcome this limitation. Various studies have used FRPs to study processes such as lexical processing, target detection and attention allocation. The goal of this study was to compare face-sensitive activity evoked by stimulus abrupt appearance with that evoked by self-controlled gaze fixations on a stimulus. Twelve participants were studied in three experimental conditions: Free-viewing (FRPs), Cued-viewing (FRPs) and Control (ERPs). We used a multiple regression approach to disentangle overlapping activity components. Our results show that the N170 face effect (face vs. non-face) is evident for the first fixation on a stimulus, whether it follows a self-generated saccade or stimulus appearance at fixation point. Furthermore, the N170 exhibits category-specific adaptation in free viewing. The N170 face effect had similar topography across viewing conditions, but there were major differences within each stimulus category. We ascribe these differences to an overlap of the fixation-related Lambda response and the N170. We tested the plausibility of this account using dipole simulations. This study establishes the use of the N170 face effect as a signature of face detection in free-viewing experiments while highlighting the importance of accounting for eye-movement related effects.

neuroscience↗

bioRxiv2019

Mnemonic prediction errors bias hippocampal states

In situations when our experience violates our predictions, it is adaptive to upregulate encoding of novel information, while down-weighting retrieval of erroneous memory predictions to promote an updated representation of the world. We asked whether mnemonic prediction errors promote distinct hippocampal processing states by leveraging recent results showing that encoding and retrieval processes are supported by distinct patterns of connectivity, or states, across hippocampal subfields. During fMRI scanning, participants were cued to retrieve well-learned room-images and were then presented with either an image identical to the learned room or a modified version (1-4 changes). We found that CA1-entorhinal connectivity increased, and CA1-CA3 connectivity decreased, with the number of changes to the learned rooms. Further, stronger memory predictions measured in CA1 during the cue correlated with the CA1-entorhinal connectivity increase in response to violations. Our findings provide a mechanism by which mnemonic prediction errors may drive memory updating - by biasing hippocampal states.

neuroscience↗