Biology subjects

Wagner, A. D.

Publications and source records attributed to Wagner, A. D..

At least 19 recordsLinked to original sources

bioRxiv2026

The Cost to Scroll: Short-form Video Use and Episodic Memory

Short-form video platforms expose users to rapid streams of novel content; these features are posited to place heavy demands on cognitive processes. In a preregistered online study, we used device-reported screen time to examine whether short-form video use is associated with sustained attention and episodic memory in participants aged 18-24 yrs (N = 502). During a sustained attention task, participants made indoor/outdoor decisions on scene stimuli, with 90% frequent trials and 10% infrequent trials; the subsequent surprise recognition test assessed memory for these items. Among participants with device-reported TikTok or Instagram use (N = 398), short-form video use was not associated with attention performance. By contrast, greater short-form video use was associated with poorer episodic memory; this relationship was driven by poorer recognition of infrequent-category items. These findings connect heavier short-form video consumption with poorer episodic memory in young adults, showing how daily digital habits co-vary with memory function.

neuroscience↗

bioRxiv2026

Dissociable structural and molecular pathways of age-related change in sustained attention

Sustained attention, the capacity to maintain goal-directed attention over extended periods, declines with age but with substantial individual variability across cognitively unimpaired (CU) older adults. We sought to determine the contributions of microstructural deterioration of the superior longitudinal fasciculus (SLF), the principal white-matter tract coupling prefrontal and parietal nodes of the dorsal attention network, as well as markers of preclinical Alzheimers disease (AD) to individual differences in sustained attention in ageing. In 162 CU older adults (mean (SD) age = 73.0 (4.9), %F = 64.8) drawn from two Stanford ageing cohorts, we measured sustained attention using the gradual-onset Continuous Performance Task (gradCPT). Performance was indexed by a composite score (Att-Z) derived from discriminability (d') and response-time variability (RTV). We used diffusion MRI tractography to quantify SLF fractional anisotropy (FA) and mean diffusivity (MD) alongside two control tracts, the corticospinal tract (CST) and cingulum (CGC). NULISA multiplex plasma immunoassays were used to measured AD-related pathology (pTau-181, pTau-217), neuroaxonal injury (NfL), and astrocytic reactivity (GFAP; plasma subsample N = 146). Parallel mediation and commonality analyses tested whether structural and plasma biomarker pathways contribute independently to individual differences in sustained attention function. Older age was associated with lower Att-Z ({beta} = -0.315, p < 0.001). In simultaneous three-tract regression models, only SLF microstructure uniquely predicted Att-Z (FA: {beta} = +0.275, p < 0.001; MD: {beta} = -0.320, p < 0.001). SLF microstructure mediated the age-attention relationship (FA indirect {beta}unstandardised = -0.01, pboot <0.01, MD indirect {beta}unstandardised = -0.009 to -0.01, pboot <0.05). Plasma pTau-181 ({beta} = -0.212, pFDR < 0.03), pTau-217 ({beta} = -0.163, pFDR < 0.05), and NfL ({beta} = -0.156, pFDR < 0.05) were negatively associated with Att-Z and each mediated effects of age on performance (pTau-181 indirect {beta}unstandardised = -0.008, pboot < 0.01; pTau-217 indirect {beta}unstandardised= -0.006, pboot< 0.05; NfL indirect {beta}unstandardised = -0.011, pboot< 0.05), whereas GFAP showed no association with sustained attention in any model. SLF microstructure was negatively associated with age (FA {beta} = -0.207, p < 0.01; MD {beta} = +0.270, p < 0.001) but was not significantly associated with plasma biomarkers (all p > 0.10). In parallel mediation models, SLF microstructure and plasma pTau exhibited significant independent indirect effects on Att-Z (SLF FA indirect {beta}unstandardised= -0.010, pboot< 0.01; SLF MD indirect {beta}unstandardised = -0.009 to -0.010, pboot< 0.05; pTau-181 indirect {beta}unstandardised = -0.008 to -0.009, pboot< 0.01; pTau-217 indirect {beta}unstandardised= -0.006 to -0.007, pboot< 0.05). Effects of NfL were attenuated when combined in a model with pTau (indirect {beta}unstandardised = -0.005 to -0.008, pboot> 0.15), suggesting shared variance among these markers. These findings reveal multiple pathways that contribute to individual differences in sustained attention in ageing that are detectable before clinical impairment, including SLF white matter integrity -- which is linked to the structural disconnection of the dorsal attention network -- and preclinical AD pathology. The independence of these pathways identifies two separable biological targets for preserving attentional capacity in CU older adults.

neuroscience↗

bioRxiv2026

Hippocampal patterns and associative memory: Distinct intracranial EEG temporal encoding patterns support memory

Episodic memory depends on neural representations encoded in the hippocampus. Experimental and computational evidence suggests that the hippocampus encodes pattern-separated representations that support later recall of episodic event elements. While extant data in humans predominantly focus on assaying the relationship between the similarity of spatial neural patterns at encoding and later memory performance, similarity of neural patterns in the temporal domain may also reveal encoding computations predictive of future memory. To examine how the similarity among temporal patterns of hippocampal activity during encoding relates to later episodic retrieval (associative cued recall and recognition memory), hippocampal activity was recorded from human participants (n=7) with implanted intracranial electrodes while they encoded arbitrary (A-B) paired-associates. Subsequent memory analyses first revealed that hippocampal high-frequency broadband power (HFB; 70-180Hz) was linked to a graded increase in memory strength; HFB power was greater during the encoding of pairs later correctly recalled relative to events later recognized and was lowest for events later forgotten. Second, and critically, subsequent memory analyses further revealed that more distinctive temporal patterns in the hippocampus during encoding -- indexed by the similarity of the HFB timeseries elicited by a given event to that elicited by other events -- were associated with superior subsequent memory performance. Finally, exploratory analyses revealed stimulus category effects on hippocampal HFB power during encoding and retrieval cuing. These results indicate that the temporal distinctiveness of hippocampal traces during encoding is important for subsequent retrieval of episodic event elements, consistent with theories that posit that pattern separation facilitates future remembering.

neuroscience↗

bioRxiv2025

Strong mnemonic prediction errors increase cognitive control, attention, and arousal

Ongoing experience is continuously processed in the context of past events. Divergence between current experience and memory-based predictions (i.e., a mnemonic prediction error; MPE) is theorized to be a signal that encoding, as opposed to retrieval, should be prioritized. We asked how MPEs place demands on control and attention-related processes, and whether these demands differ as a function of prediction strength. We investigated these questions across two experiments, wherein we recorded scalp electroencephalography and/or pupillometry as 101 young human adults performed an associative memory task. Strong MPEs, more so than weak MPEs, increased physiological indices of cognitive control (frontal theta), attention (posterior alpha and pupil size), and arousal (pupil size). Greater cognitive control (frontal theta) during strong MPEs promoted better learning of prediction violating (i.e., unexpected) stimuli. Collectively, these findings reveal multiple pathways through which the mind and brain respond adaptively to violations of strong mnemonic predictions.

neuroscience↗

bioRxiv2025

Synergistic effects of APOE ϵ4 and Alzheimer's pathology on the neural correlates of episodic remembering in cognitively unimpaired older adults

Amyloid-{beta} (A{beta}) and tau pathology begin accumulating decades before clinical symptoms and are influenced by APOE {varepsilon}4, a key genetic risk factor for Alzheimers disease (AD). Although the presence of A{beta}, tau, and APOE {varepsilon}4 are thought to impact brain function, their effects on the neural correlates of episodic memory retrieval in preclinical AD remains unknown. We investigated this question in 159 cognitively unimpaired older adults (mean age, 68.9{+/-}5.8 years; 57% female) in the Stanford Aging and Memory Study. Participants completed an associative memory task concurrent with functional MRI. A{beta} was measured using CSF A{beta}42/A{beta}40 or Florbetaben-PET imaging and tau was measured using CSF pTau181. Hippocampal univariate activity and cortical reinstatement - that is, reinstatement of patterns of neocortical activity that were present during memory encoding - were measured during successful memory retrieval. Analyses revealed that APOE {varepsilon}4 was independently associated with greater A{beta} and tau burden, and that associations of AD biomarkers with brain function and memory were moderated by APOE {varepsilon}4. Among APOE {varepsilon}4 non-carriers, A{beta} burden was linked to a pattern of hippocampal hyperactivity. Among APOE {varepsilon}4 carriers, CSF pTau181 was linked to weaker cortical reinstatement during memory retrieval and lower memory performance. Thus, abnormal AD biomarkers and genetic risk synergistically impact neural and behavioral expressions of memory in preclinical AD. These findings highlight the critical role of APOE {varepsilon}4 in moderating effects of AD pathology on brain function and identify candidate mechanisms that may contribute to increased risk of memory impairment in preclinical AD. Significance StatementHippocampus-dependent cortical reinstatement is a critical mechanism supporting episodic remembering that contributes to individual differences in memory performance in older adults. However, the contribution of early Alzheimers disease (AD) pathology to variability in this mechanism is unknown. We demonstrate that associations of AD biomarkers with hippocampal activity and cortical reinstatement are moderated by APOE {varepsilon}4 in cognitively unimpaired older adults. Amyloid-{beta}-related hyperactivity was observed in the hippocampus among APOE {varepsilon}4 non-carriers, while CSF pTau181 was linked to weaker cortical reinstatement during memory retrieval and lower memory performance among APOE {varepsilon}4 carriers. Our findings highlight synergistic effects of APOE and AD pathology on brain function and identify candidate mechanisms that may underlie increased risk of memory impairment in preclinical AD.

neuroscience↗

bioRxiv2024

Top-down attention and Alzheimer's pathology impact cortical selectivity during learning,influencing episodic memory in older adults

Human aging affects the ability to remember new experiences, in part, because of altered neural function during memory formation. One potential contributor to age-related memory decline is diminished neural selectivity -- i.e., a decline in the differential response of cortical regions to preferred vs. non-preferred stimuli during event perception -- yet the factors driving variability in neural selectivity with age remain unclear. We examined the impact of top-down attention and preclinical Alzheimers disease (AD) pathology on neural selectivity during memory encoding in 156 cognitively unimpaired older participants who underwent fMRI while performing a word-face and word-scene associative memory task. Neural selectivity in face- and place-selective cortical regions was greater during events that were later remembered compared to forgotten. Critically, neural selectivity during learning positively scaled with memory-related variability in top-down attention, whereas selectivity negatively related to early AD pathology, evidenced by elevated plasma pTau181. Path analysis revealed that neural selectivity at encoding mediated the effects of age, top-down attention, and pTau181 on associative memory. Collectively, these data reveal multiple pathways that contribute to memory differences among older adults -- AD-independent reductions in top-down attention and AD-related pathology alter the precision of cortical representations of events during experience, with consequences for remembering.

neuroscience↗

bioRxiv2024

Using Repeated Lysis Steps Fractionates Between Heterotrophic and Cyanobacterial DNA Extracted from Xenic Cyanobacterial Cultures

Extracting DNA from cyanobacteria can be a challenge because of their diverse morphologies, challenging cellular structure, and the heterotrophic microbiome often present within cyanobacterial cultures. As such, even when our DNA yields are sufficient for sequencing, the percentage of reads coming from the cyanobacterial host can be low, leading to incomplete genomes spread across several scaffolds. In this research, we optimized a DNA isolation protocol using three iterative cell lysis steps to enrich the portion of DNA isolated coming from the cyanobacterial host rather than the heterotrophic microbiome. In order to utilize in-house nanopore sequencing, we faced a challenge in that our lysis protocol led to DNA shearing and a lower molecular weight DNA extract than is suitable for this sequencing technology. As such we used two bead-based size selection steps to remove shorter molecules of DNA before nanopore sequencing. EPI2ME analysis of the processed reads from the iterative lysis steps showed that in the first lysis the heterotrophic microbiome could make up more than half of all reads, but with each lysis the proportion of reads coming from these other species decreased. Using our iterative lysis protocol, we were able to sequence the genomes of two cyanobacteria isolated from fresh water sources around northern Mississippi, namely Leptolyngbya sp. BL-A-14 and Limnothrix sp. BL-A-16. The genomes of these isolates were assembled as closed chromosomes of 7.2 and 4.5 Mb for Leptolyngbya sp. BL-A-14 and Limnothrix sp. BL-A-16, respectively. Because some cyanobacteria have symbioses with their heterotrophic microbiome it is not always possible to prepare axenic cultures of these organisms, we hope our approach will be useful for sequencing xenic cultures of cyanobacteria, but we can also imagine applications in studying this microbiome specifically by focusing sequencing efforts on the first fraction.

genomics↗

bioRxiv2024

Synapse protein signatures in cerebrospinal fluid and plasma predict cognitive maintenance versus decline in Alzheimers disease

Rates of cognitive decline in Alzheimers disease (AD) are extremely heterogeneous, with ages of symptom onset ranging from age 40-100 years and conversion from mild cognitive impairment to AD dementia taking 2-20 years. Development of biomarkers for amyloid-beta (A{beta}) and tau protein aggregates, the hallmark pathologies of AD, have improved patient monitoring/stratification and drug development, but they still only explain 20-40% of the variance in cognitive impairment (CI) in AD. To discover additional molecular drivers and biomarkers of AD dementia, we perform cerebrospinal fluid (CSF) proteomics on 3,416 individuals from six deeply phenotyped prospective AD case-control cohorts. We identify synapse proteins as the strongest correlates of CI, independent of A{beta} and tau. Using machine learning we derive the CSF YWHAG:NPTX2 synapse protein ratio, a robust correlate of CI, which explains 27% of the variance in CI beyond CSF PTau181:A{beta}42, 10% beyond tau PET, and 50% beyond CSF NfL in A{beta} positive individuals. We find YWHAG:NPTX2 also increases with normal aging as early as age 20 and increases at a faster rate in APOE4 carriers and autosomal dominant-AD mutation carriers. Most notably, YWHAG:NPTX2+ individuals (top 25th percentile) are 15-times (HR=15.4 [10.6-22.2]) more likely to experience cognitive decline over 15 years compared to YWHAG:NPTX2- individuals (bottom 25th percentile), and this rises to 19-times (HR=18.9 [10.83-32.9]) with additional stratification by A{beta} and phosphorylated tau status. Lastly, we perform plasma proteomics on 4,245 individuals to develop a plasma-based signature of CI which partly recapitulates CSF YWHAG:NPTX2. Overall, our findings underscore CSF YWHAG:NPTX2 and the corresponding plasma signature as robust prognostic biomarkers for AD onset and progression beyond gold-standard biomarkers of A{beta}, tau, and neurodegeneration and implicate synapse dysfunction as a core driver of AD dementia.

neuroscience↗

bioRxiv2024

Post-retrieval noradrenergic activation impairs subsequent memory depending on cortico-hippocampal reactivation

When retrieved, seemingly stable memories can become sensitive to significant events, such as acute stress. The mechanisms underlying these memory dynamics remain poorly understood. Here we show that noradrenergic stimulation after memory retrieval impairs subsequent remembering, depending on hippocampal and cortical signals emerging during retrieval. In a three-day study, we measured brain activity using fMRI during initial encoding, 24h-delayed memory cueing followed by pharmacological elevations of glucocorticoid or noradrenergic activity, and final recall. While post-retrieval glucocorticoids did not affect subsequent memory, the impairing effect of noradrenergic arousal on final recall depended on hippocampal reactivation and category-level reinstatement in ventral temporal cortex during memory cueing. These effects did not require a reactivation of the original memory trace and did not interact with offline reinstatement during rest. Our findings demonstrate that, depending on the retrieval-related neural reactivation of memories, noradrenergic arousal after retrieval can alter the future accessibility of consolidated memories.

neuroscience↗

bioRxiv2023

Medial temporal cortex supports compositional visual inferences

Perception unfolds across multiple timescales. For humans and other primates, many object-centric visual attributes can be inferred at a glance (i.e., given <200ms of visual information), an ability supported by ventral temporal cortex (VTC). Other perceptual inferences require more time; to determine a novel objects identity, we might need to represent its unique configuration of visual features, requiring multiple glances. Here we evaluate whether perirhinal cortex (PRC), downstream from VTC, supports object perception by integrating over such visuospatial sequences. We first compare human visual inferences directly to electrophysiological recordings from macaque VTC. While human performance at a glance is approximated by a linear readout of VTC, participants radically outperform VTC given longer viewing times (i.e., >200ms). Next, we leverage a stimulus set that enables us to characterize PRC involvement in these temporally extended visual inferences. We find that human visual inferences at a glance resemble the deficits observed in PRC-lesioned human participants. Not surprisingly, by measuring gaze behaviors during these temporally extended viewing periods, we find that participants sequentially sample task-relevant features via multiple saccades/fixations. These patterns of visuospatial attention are both reliable across participants and necessary for PRC-dependent visual inferences. These data reveal complementary neural systems that support visual object perception: VTC provides a rich set of visual features at a glance, while PRC is able to integrate over the sequential outputs of VTC to support object-level inferences.

neuroscience↗

bioRxiv2023

Cross regional coordination of neural activity in the human brain during autobiographical self-referential processing

For the human mind to operate, populations of neurons across remote regions of the brain need to coordinate their activity in the subsecond temporal scale. To date, our knowledge of such fast interactions involving cortical and subcortical structures in large brains, such as the human brain, remains limited. Here, we used stereo-electroencephalography (sEEG) recordings across four brain regions that are known, from decades of work, to be important for autobiographical memory processing. Our recordings involved 31 human participants implanted with intracranial electrodes in the hippocampus (HPC), posteromedial cortex (PMC), and ventromedial, as well as orbital subregions of the prefrontal cortex (OFC). In 14 subjects, we also recorded simultaneously in the anterior thalamus (ANT) across various experimental conditions and with direct electrical stimulations. Our observations provide new lines of correlative and causal evidence about the spatiotemporal profile of oscillatory coordination of cortical and subcortical activity during self-referential memory-based processing.

neuroscience↗

bioRxiv2023

When multi-voxel pattern similarity and global activation are intertwined: Approaches to disentangling correlation from activation

Pattern similarity analysis, which uses correlation to examine similarities between neural activation patterns evoked by different trials or conditions, is often leveraged to test hypotheses not easily answerable with univariate comparisons, such as how events are represented or processed and the relationships between representations or processing of events. In principle, univariate analyses of global activation and multivariate analyses of pattern similarity can be used to answer substantively different questions about psychological and neural processing. For this to hold, it is necessary that pattern similarity estimates are not contaminated by differences in global activation across experimental events. Here, we report simulated data that demonstrate that global activation and pattern similarity (as assessed by correlation), although theoretically independent, are often intertwined. We present two plausible scenarios that illustrate how condition-specific changes in global activation can elicit condition-specific increases in pattern similarity by interacting with underlying across-voxel activation patterns. First, we consider a scenario in which a target region contains subpopulations of voxels such that only some voxels in a region are sensitive to a psychological variable and the remaining voxels are not modulated by this variable. In this scenario, this spatial pattern of responsive and unresponsive voxels adds new, shared across-voxel variability for events in the active condition, thereby increasing pattern similarity between these events. Second, we consider a scenario in which trials from all conditions elicit a shared across-voxel pattern of activation, but this shared across-voxel pattern is amplified for trials within one condition due to greater global activation. In this scenario, the change in activation for a given condition increases the ability to detect pre-existing, shared across-voxel variability across events in that condition, thereby increasing pattern similarity between these events. Given the observed influence of global activation on pattern similarity, we then assess whether it is possible to statistically separate the contributions of global activation and pattern similarity to observed activation patterns (using regression approaches, matching activation across conditions, and inclusion of control conditions). Additional simulations demonstrate that use of these techniques is not always effective in removing the influence of global activation on pattern similarity --the efficacy of these techniques depends on a variety of signal parameters that will likely vary across experiments and participants, highlighting the need for tailored control analyses that are targeted at addressing the particular hypotheses and potential global activation confounds of a given experiment. [Note: The reported simulations and this resulting white paper were generated in 2014. We share, without update, this paper given the continued relevance of understanding and controlling for global activation confounds when conducting multi-variate pattern analyses.]

neuroscience↗

bioRxiv2022

Representational integration and differentiation in the human hippocampus following goal-directed navigation

As we learn, dynamic memory processes build structured knowledge across our experiences. Such knowledge enables the formation of internal models of the world that we use to plan, make decisions, and act. Recent theorizing posits that mnemonic mechanisms of differentiation and integration - which at one level may seem to be at odds - both contribute to the emergence of structured knowledge. We tested this possibility using fMRI as human participants learned to navigate within local and global virtual environments over the course of three days. Pattern similarity analyses on entorhinal cortex, hippocampus, and ventromedial prefrontal cortex patterns revealed evidence that differentiation and integration work concurrently to build local and global environmental representations, and that variability in integration relates to differences in navigation efficiency. These results offer new insights into the neural machinery and the underlying mechanisms that translate experiences into structured knowledge that allows us to navigate to achieve goals.

neuroscience↗

bioRxiv2020

Representations of local spatial information in the human medial temporal lobe duringmemory-guided navigation

The hippocampus (HC) and surrounding medial temporal lobe (MTL) cortical regions play a critical role in spatial navigation and episodic memory. However, it remains unclear how the interaction between the HCs conjunctive coding and mnemonic differentiation contributes to neural representations of spatial environments. Multivariate functional magnetic resonance imaging (fMRI) analyses enable examination of how human HC and MTL cortical regions encode multidimensional spatial information to support memory-guided navigation. We combined high-resolution fMRI with a virtual navigation paradigm in which participants relied on memory of the environment to navigate to goal locations in two different virtual rooms. Within each room, participants were cued to navigate to four learned locations, each associated with one of two reward values. Pattern similarity analysis revealed that when participants successfully arrived at goal locations, activity patterns in HC and parahippocampal cortex (PHC) represented room-goal location conjunctions and activity patterns in HC subfields represented room-reward-location conjunctions. These results add to an emerging literature revealing hippocampal conjunctive representations during goal-directed behavior.

animal behavior and cognition↗

bioRxiv2020

When the ventral visual stream is not enough: A deep learning account of medial temporal lobe involvement in perception

The medial temporal lobe (MTL) supports a constellation of memory-related behaviors. Its involvement in perceptual processing, however, has been subject to enduring debate. This debate centers on perirhinal cortex (PRC), an MTL structure at the apex of the ventral visual stream (VVS). Here we leverage a deep learning framework that approximates visual behaviors supported by the VVS--i.e. lacking PRC. We first apply this approach retroactively, modeling 30 published visual discrimination experiments: Excluding non-diagnostic stimulus sets, there is a striking correspondence between VVS-modeled and PRC-lesioned behavior, while each are outperformed by PRC-intact participants. We corroborate and extend these results with a novel experiment, directly comparing PRC-intact human performance to electrophysiological recordings from the macaque VVS: PRC-intact participants outperform a linear readout of high-level visual cortex. By situating lesion, electrophysiological, and behavioral results within a shared computational framework, this work resolves decades of seemingly inconsistent findings surrounding PRC involvement in perception.

neuroscience↗

bioRxiv2020

Hippocampal and cortical mechanisms at retrieval explain variability in episodic remembering in older adults

Age-related episodic memory decline is characterized by striking heterogeneity across individuals. Hippocampal pattern completion is a fundamental process supporting episodic memory. Yet, the degree to which this mechanism is impaired with age, and contributes to variability in episodic memory, remains unclear. We combine univariate and multivariate analyses of fMRI data from a large cohort of cognitively normal older adults (N=100; 60-82 yrs) to measure hippocampal activity and cortical reinstatement during retrieval of trial-unique associations. Trial-wise analyses revealed that hippocampal activity predicted cortical reinstatement strength, and these two metrics of pattern completion independently predicted retrieval success. However, increased age weakened cortical reinstatement and its relationship to memory behaviour. Critically, individual differences in the strength of hippocampal activity and cortical reinstatement explained unique variance in performance across multiple assays of episodic memory. These results indicate that fMRI indices of hippocampal pattern completion explain within- and across-individual memory variability in older adults.

neuroscience↗

bioRxiv2019

Content tuning in the medial temporal lobe cortex: Voxels that perceive, retrieve

How do we recall vivid details from our past based only on sparse cues? Research suggests that the phenomenological reinstatement of past experiences is accompanied by neural reinstatement of the original percept. This process critically depends on the medial temporal lobe (MTL). Within the MTL, perirhinal cortex (PRC) and parahippocampal cortex (PHC) are thought to support encoding and recall of objects and scenes, respectively, with the hippocampus (HC) serving as a content-independent hub. If the fidelity of recall indeed arises from neural reinstatement of perceptual activity, then successful recall should preferentially draw upon those neural populations within content-sensitive MTL cortex that are tuned to the same content during perception. We tested this hypothesis by having eighteen human participants undergo functional magnetic resonance imaging (fMRI) while they encoded and recalled objects and scenes paired with words. Critically, recall was cued with the words only. While HC distinguished successful from unsuccessful recall of both objects and scenes, PRC and PHC were preferentially engaged during successful vs. unsuccessful object and scene recall, respectively. Importantly, within PRC and PHC, this content-sensitive recall was predicted by content tuning during perception: Across PRC voxels, we observed a positive linear relationship between object tuning during perception and successful object recall, while across PHC voxels, we observed a positive linear relationship between scene tuning during perception and successful scene recall. Our results thus highlight content-based roles of MTL cortical regions for episodic memory and reveal a direct mapping between content-specific tuning during perception and successful recall.

neuroscience↗

bioRxiv2018

Hippocampal Pattern Separation Supports Reinforcement Learning

1Animals rely on learned associations to make decisions. Associations can be based on relationships between object features (e.g., the three-leaflets of poison ivy leaves) and outcomes (e.g., rash). More often, outcomes are linked to multidimensional states (e.g., poison ivy is green in summer but red in spring). Feature-based reinforcement learning fails when the values of individual features depend on the other features present. One solution is to assign value to multifeatural conjunctive representations. We tested if the hippocampus formed separable conjunctive representations that enabled learning of response contingencies for stimuli of the form: AB+, B-, AC-, C+. Pattern analyses on functional MRI data showed the hippocampus formed conjunctive representations that were dissociable from feature components and that these representations influenced striatal PEs. Our results establish a novel role for hippocampal pattern separation and conjunctive representation in reinforcement learning.

neuroscience↗