Structure and function of the hippocampal CA3 module.

The hippocampal formation is crucial for learning and memory, with submodule CA3 thought to be the substrate of pattern completion. However, the underlying synaptic and computational mechanisms of this network are not well understood. Here, we perform circuit reconstruction of a CA3 module using three dimensional (3D) electron microscopy data and combine this with functional connectivity recordings and computational simulations to determine possible CA3 network mechanisms. Direct measurements of connectivity schemes with both physiological measurements and structural 3D EM revealed a high connectivity rate, multi-fold higher than previously assumed. Mathematical modelling indicated that such CA3 networks can robustly generate pattern completion and replay memory sequences. In conclusion, our data demonstrate that the connectivity scheme of the hippocampal submodule is well suited for efficient memory storage and retrieval.

Sleep shapes the associative structure underlying pattern completion in multielement event memory.

Sleep supports the consolidation of episodic memory. It is, however, a matter of ongoing debate how this effect is established, because, so far, it has been demonstrated almost exclusively for simple associations, which lack the complex associative structure of real-life events, typically comprising multiple elements with different association strengths. Because of this associative structure interlinking the individual elements, a partial cue (e.g., a single element) can recover an entire multielement event. This process, referred to as pattern completion, is a fundamental property of episodic memory. Yet, it is currently unknown how sleep affects the associative structure within multielement events and subsequent processes of pattern completion. Here, we investigated the effects of post-encoding sleep, compared with a period of nocturnal wakefulness (followed by a recovery night), on multielement associative structures in healthy humans using a verbal associative learning task including strongly, weakly, and not directly encoded associations. We demonstrate that sleep selectively benefits memory for weakly associated elements as well as for associations that were not directly encoded but not for strongly associated elements within a multielement event structure. Crucially, these effects were accompanied by a beneficial effect of sleep on the ability to recall multiple elements of an event based on a single common cue. In addition, retrieval performance was predicted by sleep spindle activity during post-encoding sleep. Together, these results indicate that sleep plays a fundamental role in shaping associative structures, thereby supporting pattern completion in complex multielement events.

Iron Deposition and Distribution Across the Hippocampus Is Associated with Pattern Separation and Pattern Completion in Older Adults at Risk for Alzheimer's Disease.

Elevated iron deposition in the brain has been observed in older adult humans and persons with Alzheimer's disease (AD), and has been associated with lower cognitive performance. We investigated the impact of iron deposition, and its topographical distribution across hippocampal subfields and segments (anterior, posterior) measured along its longitudinal axis, on episodic memory in a sample of cognitively unimpaired older adults at elevated familial risk for AD (N = 172, 120 females, 52 males; mean age = 68.8 ± 5.4 years). MRI-based quantitative susceptibility maps were acquired to derive estimates of hippocampal iron deposition. The Mnemonic Similarity Task was used to measure pattern separation and pattern completion, two hippocampally mediated episodic memory processes. Greater hippocampal iron load was associated with lower pattern separation and higher pattern completion scores, both indicators of poorer episodic memory. Examination of iron levels within hippocampal subfields across its long axis revealed topographic specificity. Among the subfields and segments investigated here, iron deposition in the posterior hippocampal CA1 was the most robustly and negatively associated with the fidelity memory representations. This association remained after controlling for hippocampal volume and was observed in the context of normal performance on standard neuropsychological memory measures. These findings reveal that the impact of iron load on episodic memory performance is not uniform across the hippocampus. Both iron deposition levels as well as its spatial distribution, must be taken into account when examining the relationship between hippocampal iron and episodic memory in older adults at elevated risk for AD.

Event Integration and Temporal Differentiation: 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. We asked if and how distinct hippocampal subfields come to hierarchically and, in parallel, represent both event context and subevent occurrences with learning. Female and male human 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. 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 (DG), 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 DG. Additional similarity measures support the notion that CA3 clustered representations reflect shared voxel populations, while DG's distinct item representations reflect different voxel populations. These findings suggest an interplay between temporal differentiation in the DG and attractor dynamics in CA3. They advance our understanding of how knowledge is structured through integration and separation across time and context.

Individual differences in visual pattern completion predict adaptation to degraded speech.

Recognizing acoustically degraded speech relies on predictive processing whereby incomplete auditory cues are mapped to stored linguistic representations via pattern recognition processes. While listeners vary in their ability to recognize degraded speech, performance improves when a written transcription is presented, allowing completion of the partial sensory pattern to preexisting representations. Building on work characterizing predictive processing as pattern completion, we examined the relationship between domain-general pattern recognition and individual variation in degraded speech learning. Participants completed a visual pattern recognition task to measure individual-level tendency towards pattern completion. Participants were also trained to recognize noise-vocoded speech with written transcriptions and tested on speech recognition pre- and post-training using a retrieval-based transcription task. Listeners significantly improved in recognizing speech after training, and pattern completion on the visual task predicted improvement for novel items. The results implicate pattern completion as a domain-general learning mechanism that can facilitate speech adaptation in challenging contexts.