Episodic memories typically comprise multiple elements. A defining characteristic of episodic retrieval is holistic recollection, i.e., comprehensive recall of the elements a memorized event encompasses. A recent study implicated activity in the human hippocampus with holistic recollection of multi-element events based on cues (Horner et al., 2015). Here, we obtained ultra-high resolution functional neuroimaging data at 7 tesla in 30 younger adults (12 female) using the same paradigm. In accordance with anatomically inspired computational models and animal research, we found that metabolic activity in hippocampal subfield CA3 (but less pronounced in dentate gyrus) correlated with this form of mnemonic pattern completion across participants. Our study provides the first evidence in humans for a strong involvement of hippocampal subfield CA3 in holistic recollection via pattern completion.SIGNIFICANCE STATEMENT Memories of daily events usually involve multiple elements, although a single element can be sufficient to prompt recollection of the whole event. Such holistic recollection is thought to require reactivation of brain activity representing the full event from one event element (“pattern completion”). Computational and animal models suggest that mnemonic pattern completion is accomplished in a specific subregion of the hippocampus called CA3, but empirical evidence in humans was lacking. Here, we leverage the ultra-high resolution of 7 tesla neuroimaging to provide first evidence for a strong involvement of the human CA3 in holistic recollection of multi-element events via pattern completion.

Sensitive and frequent digital remote memory assessments via mobile devices hold the promise to facilitate the detection of cognitive impairment and decline. However, in order to be successful at scale, cognitive tests need to be applicable in unsupervised settings and confounding factors need to be understood. This study explored the feasibility of completely unsupervised digital cognitive assessments using three novel memory tasks in a Citizen Science project across Germany. To that end, the study aimed to identify factors associated with stronger participant retention, to examine test-retest reliability and the extent of practice effects, as well as to investigate the influence of uncontrolled settings such as time of day, delay between sessions or screen size on memory performance. A total of 1,407 adults (aged 18–89) participated in the study for up to 12 weeks, completing weekly memory tasks in addition to short questionnaires regarding sleep duration, subjective cognitive complaints as well as cold symptoms. Participation across memory tasks was pseudorandomized such that individuals were assigned to one of three memory paradigms resulting in three otherwise identical sub-studies. One hundred thirty-eight participants contributed to two of the three paradigms. Critically, for each memory task 12 independent parallel test sets were used to minimize effects of repeated testing. First, we observed a mean participant retention time of 44 days, or 4 active test sessions, and 77.5% compliance to the study protocol in an unsupervised setting with no contact between participants and study personnel, payment or feedback. We identified subject-level factors that contributed to higher retention times. Second, we found minor practice effects associated with repeated cognitive testing, and reveal evidence for acceptable-to-good retest reliability of mobile testing. Third, we show that memory performance assessed through repeated digital assessments was strongly associated with age in all paradigms, and individuals with subjectively reported cognitive decline presented lower mnemonic discrimination accuracy compared to non-complaining participants. Finally, we identified design-related factors that need to be incorporated in future studies such as the time delay between test sessions. Our results demonstrate the feasibility of fully unsupervised digital remote memory assessments and identify critical factors to account for in future studies.

The perirhinal cortex is situated on the border between sensory association cortex and the hippocampal formation. It serves an important function as a transition area between the sensory neocortex and the medial temporal lobe. While the perirhinal cortex has traditionally been associated with object coding and the "what" pathway of the temporal lobe, current evidence suggests a broader function of the perirhinal cortex in solving feature ambiguity and processing complex stimuli. Besides fulfilling functions in object coding, recent neurophysiological findings in freely moving rodents indicate that the perirhinal cortex also contributes to spatial and contextual processing beyond individual sensory modalities. Here, we address how these two opposing views on perirhinal cortex-the object-centered and spatial-contextual processing hypotheses-may be reconciled. The perirhinal cortex is consistently recruited when different features can be merged perceptually or conceptually into a single entity. Features that are unitized in these entities include object information from multiple sensory domains, reward associations, semantic features and spatial/contextual associations. We propose that the same perirhinal network circuits can be flexibly deployed for multiple cognitive functions, such that the perirhinal cortex performs similar unitization operations on different types of information, depending on behavioral demands and ranging from the object-related domain to spatial, contextual and semantic information.