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result(s) for
"Brice, A."
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Perception and memory have distinct spatial tuning properties in human visual cortex
by
Favila, Serra E.
,
Kuhl, Brice A.
,
Winawer, Jonathan
in
631/378/1595/2167
,
631/378/2613
,
Behavior
2022
Reactivation of earlier perceptual activity is thought to underlie long-term memory recall. Despite evidence for this view, it is unclear whether mnemonic activity exhibits the same tuning properties as feedforward perceptual activity. Here, we leverage population receptive field models to parameterize fMRI activity in human visual cortex during spatial memory retrieval. Though retinotopic organization is present during both perception and memory, large systematic differences in tuning are also evident. Whereas there is a three-fold decline in spatial precision from early to late visual areas during perception, this pattern is not observed during memory retrieval. This difference cannot be explained by reduced signal-to-noise or poor performance on memory trials. Instead, by simulating top-down activity in a network model of cortex, we demonstrate that this property is well explained by the hierarchical structure of the visual system. Together, modeling and empirical results suggest that computational constraints imposed by visual system architecture limit the fidelity of memory reactivation in sensory cortex.
Neural activity from perception is thought to be reactivated during memory recall. Here, the authors show that memory reactivation in visual cortex exhibits different tuning properties from those observed during perception.
Journal Article
An adaptive peptide-binding site in ubiquitin receptor hRpn13 revealed by structural studies
by
Wilson, Brice A. P.
,
Walters, Kylie J.
,
Chandravanshi, Monika
in
101/6
,
119/118
,
631/45/474/2085
2025
A pleckstrin-like receptor for ubiquitin (Pru) domain in hRpn13 binds ubiquitin and proteasome subunit hRpn2. Here, we report a crystal structure of Pru bound to amino acids at the extreme N-terminus (ENT) of recombinant hRpn13. ENT adopts a U shape with native sequence along one side where M1 is buried in a Pru W108-centered pocket, and non-native sequence along the other with main chain hydrogen bonding to a neighboring Pru of the crystal lattice. These ENT:Pru interactions are stable in molecular dynamics simulations even with inclusion of only one Pru. Our findings suggest that hRpn13 can form bidentate interactions with ubiquitinated substrates by binding to both ubiquitin chains and disordered sequences of substrates. Testing this model by solution nuclear magnetic resonance revealed Pru to bind weakly to various peptides, concurrent binding with ubiquitin, and ENT displacement by hRpn2, the latter required for substrate handoff to the proteasome ATPases.
Rpn13 helps proteasomes capture ubiquitinated substrates. Here, the authors find that as Rpn13 binds to ubiquitin chains, it can interact broadly with disordered segments in the substrate. These low affinity interactions are lost as Rpn13 binds proteasomes to enable a substrate hand-off mechanism.
Journal Article
Sesquiterpene Coumarin Ethers and Phenylpropanoids from the Roots of Ferula drudeana, the Putative Anatolian Ecotype of the Silphion Plant
by
Wilson, Brice A. P.
,
Pruett, Nathanael
,
Wang, Dongdong
in
Antineoplastic Agents, Phytogenic - chemistry
,
Antineoplastic Agents, Phytogenic - isolation & purification
,
Antineoplastic Agents, Phytogenic - pharmacology
2025
Four new sesquiterpene coumarin ethers (1–4) and a new phenylpropanoid compound (5) were isolated from a hexane extract of the roots of Ferula drudeana, the putative Anatolian ecotype of the silphion plant, in addition to nineteen previously described sesquiterpene coumarins (6–24) and four known phenylpropanoid derivatives (25–28). The structures of these compounds were elucidated by extensive spectroscopic analysis and computational studies. The cytotoxic activities of all isolated compounds were evaluated on renal, malignant pleural mesothelioma (MPM) and colon cancer cell lines. While 11 sesquiterpene coumarin derivatives showed strong-to-moderate cytotoxic activity against the UO31 renal cancer cell line, 13 compounds showed strong cytotoxic activity against the MPM cell line, and four sesquiterpene coumarin derivatives displayed moderate cytotoxic activity against the colon cancer cell line.
Journal Article
Mapping multidimensional content representations to neural and behavioral expressions of episodic memory
by
Wang, Yingying
,
Kuhl, Brice A.
,
Lee, Hongmi
in
Activity patterns
,
Brain Mapping
,
Cortex (parietal)
2023
•We used encoding models to map semantic content to fMRI activity patterns.•Visual and parietal cortex yielded reconstructions of viewed and recalled content.•Parietal reconstructions were invariant to content format (viewed, recalled).•fMRI reconstructions of recalled content aligned with measures of verbal recall.•Ventral temporal cortex reconstructions predicted idiosyncratic details in recall.
Human neuroimaging studies have shown that the contents of episodic memories are represented in distributed patterns of neural activity. However, these studies have mostly been limited to decoding simple, unidimensional properties of stimuli. Semantic encoding models, in contrast, offer a means for characterizing the rich, multidimensional information that comprises episodic memories. Here, we extensively sampled four human fMRI subjects to build semantic encoding models and then applied these models to reconstruct content from natural scene images as they were viewed and recalled from memory. First, we found that multidimensional semantic information was successfully reconstructed from activity patterns across visual and lateral parietal cortices, both when viewing scenes and when recalling them from memory. Second, whereas visual cortical reconstructions were much more accurate when images were viewed versus recalled from memory, lateral parietal reconstructions were comparably accurate across visual perception and memory. Third, by applying natural language processing methods to verbal recall data, we showed that fMRI-based reconstructions reliably matched subjects’ verbal descriptions of their memories. In fact, reconstructions from ventral temporal cortex more closely matched subjects’ own verbal recall than other subjects’ verbal recall of the same images. Fourth, encoding models reliably transferred across subjects: memories were successfully reconstructed using encoding models trained on data from entirely independent subjects. Together, these findings provide evidence for successful reconstructions of multidimensional and idiosyncratic memory representations and highlight the differential sensitivity of visual cortical and lateral parietal regions to information derived from the external visual environment versus internally-generated memories.
Journal Article
Re-expression of CA1 and entorhinal activity patterns preserves temporal context memory at long timescales
2023
Converging, cross-species evidence indicates that memory for time is supported by hippocampal area CA1 and entorhinal cortex. However, limited evidence characterizes how these regions preserve temporal memories over long timescales (e.g., months). At long timescales, memoranda may be encountered in multiple temporal contexts, potentially creating interference. Here, using 7T fMRI, we measured CA1 and entorhinal activity patterns as human participants viewed thousands of natural scene images distributed, and repeated, across many months. We show that memory for an image’s original temporal context was predicted by the degree to which CA1/entorhinal activity patterns from the first encounter with an image were re-expressed during re-encounters occurring minutes to months later. Critically, temporal memory signals were dissociable from predictors of recognition confidence, which were carried by distinct medial temporal lobe expressions. These findings suggest that CA1 and entorhinal cortex preserve temporal memories across long timescales by coding for and reinstating temporal context information.
How hippocampal area CA1 and the entorhinal cortex preserve temporal memories over long timescales is not known. Here, the authors show using 7T fMRI, that temporal context memory for scene images is predicted by the re-expression of CA1 and entorhinal cortex activity patterns during subsequent encounters over a period of months.
Journal Article
Experience-dependent hippocampal pattern differentiation prevents interference during subsequent learning
by
Chanales, Avi J. H.
,
Favila, Serra E.
,
Kuhl, Brice A.
in
59/36
,
631/378/1595/1554
,
Humanities and Social Sciences
2016
The hippocampus is believed to reduce memory interference by disambiguating neural representations of similar events. However, there is limited empirical evidence linking representational overlap in the hippocampus to memory interference. Likewise, it is not fully understood how learning influences overlap among hippocampal representations. Using pattern-based fMRI analyses, we tested for a bidirectional relationship between memory overlap in the human hippocampus and learning. First, we show that learning drives hippocampal representations of similar events apart from one another. These changes are not explained by task demands to discriminate similar stimuli and are fully absent in visual cortical areas that feed into the hippocampus. Second, we show that lower representational overlap in the hippocampus benefits subsequent learning by preventing interference between similar memories. These findings reveal targeted experience-dependent changes in hippocampal representations of similar events and provide a critical link between memory overlap in the hippocampus and behavioural expressions of memory interference.
There is limited evidence linking learning related changes in hippocampal representations and memory interference. Here Favila and colleagues demonstrate that learning reduces overlap in hippocampal activity patterns corresponding to similar events, which benefits subsequent learning by preventing interference.
Journal Article
Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants
by
Li, Shuwei
,
Sarver, Brice A. J.
,
Cabrera-Socorro, Alfredo
in
Alzheimer Disease
,
Alzheimer's disease
,
APOE-Christchurch variant
2023
Keywords: APOE-Christchurch variant, Alzheimer's disease, Rare variants
Journal Article
Interference between overlapping memories is predicted by neural states during learning
by
Chanales, Avi J. H.
,
Dudukovic, Nicole M.
,
Richter, Franziska R.
in
59/36
,
631/378/116/2394
,
631/378/1595
2019
One of the primary contributors to forgetting is interference from overlapping memories. Intuitively, this suggests—and prominent theoretical models argue—that memory interference is best avoided by encoding overlapping memories as if they were unrelated. It is therefore surprising that reactivation of older memories during new encoding has been associated with reduced memory interference. Critically, however, prior studies have not directly established why reactivation reduces interference. Here, we first developed a behavioral paradigm that isolates the negative influence that overlapping memories exert during memory retrieval. We then show that reactivating older memories during the encoding of new memories dramatically reduces this interference cost at retrieval. Finally, leveraging multiple fMRI decoding approaches, we show that spontaneous reactivation of older memories during new encoding leads to integration of overlapping memories and, critically, that integration during encoding specifically reduces interference between overlapping, and otherwise competing, memories during retrieval.
Interference from overlapping memories can cause forgetting. Here, the authors show using fMRI decoding approaches that spontaneous reactivation of older memories during new encoding leads to integration, and less interference, between overlapping items.
Journal Article
Abrupt hippocampal remapping signals resolution of memory interference
by
Molitor, Robert J.
,
Kim, Ghootae
,
Favila, Serra E.
in
59/36
,
631/378/1595/1554
,
631/378/1595/2167
2021
Remapping refers to a decorrelation of hippocampal representations of similar spatial environments. While it has been speculated that remapping may contribute to the resolution of episodic memory interference in humans, direct evidence is surprisingly limited. We tested this idea using high-resolution, pattern-based fMRI analyses. Here we show that activity patterns in human CA3/dentate gyrus exhibit an abrupt, temporally-specific decorrelation of highly similar memory representations that is precisely coupled with behavioral expressions of successful learning. The magnitude of this learning-related decorrelation was predicted by the amount of pattern overlap during initial stages of learning, with greater initial overlap leading to stronger decorrelation. Finally, we show that remapped activity patterns carry relatively more information about learned episodic associations compared to competing associations, further validating the learning-related significance of remapping. Collectively, these findings establish a critical link between hippocampal remapping and episodic memory interference and provide insight into why remapping occurs.
When two memories are similar, their encoding and retrieval can be disrupted by each other. Here the authors show that memory interference is resolved through abrupt remapping of activity patterns in the human hippocampal CA3 and dentate gyrus.
Journal Article