The hippocampus plays an important role in representing spatial locations and sequences and in transforming representations. How these representational structures and operations support memory for the temporal order of random items is still poorly understood. We addressed this question by leveraging the method of loci, a powerful mnemonic strategy for temporal order memory that particularly recruits hippocampus-dependent computations of spatial locations and associations. Applying representational similarity analysis to functional magnetic resonance imaging activation patterns revealed that hippocampal subfields contained representations of multiple features of sequence structure, including spatial locations, location distance, and sequence boundaries, as well as episodic-like temporal context. Critically, the hippocampal CA1 exhibited spatial transformation of representational patterns, showing lower pattern similarity for items in same locations than closely matched different locations during retrieval, whereas the CA23DG exhibited sequential transformation of representational patterns, showing lower pattern similarity for items in near locations than in far locations during encoding. These transformations enabled the encoding of multiple items in the same location and disambiguation of adjacent items. Our results suggest that the hippocampus can flexibly reconfigure multiplexed event structure representations to support accurate temporal order memory.
Chemo-photothermal combination therapy could achieve synergistically enhanced efficiency against tumors. Nanocarriers with good safety and high efficiency for chemo- photothermal therapy are pressingly needed. A new type of hydroxyethyl starch (HES) based on nanoparticles (NPs) loaded with doxorubicin (DOX) and indocyanine green (ICG) was, thus, developed in this study. DOX-loaded HES conjugates with redox-sensitivity (HES-SS-DOX) were first synthesized and they were then combined with ICG to self-assemble into HES-SS-DOX@ICG NPs with controlled compositions and sizes via collaborative interactions. The optimal HES-SS-DOX@ICG NPs had good physical and photothermal stability in aqueous media and showed high photothermal efficiency in vivo. They were able to fast release the loaded DOX in response to the redox stimulus and the applied laser irradiation. Based on the H22-tumor-bearing mouse model, these NPs were found to tendentiously accumulate inside tumors in comparison to other major organs. The HES-SS-DOX@ICG NPs together with dose-designated laser irradiation were able to fully eradicate tumors with only one injection and one single subsequent laser irradiation on the tumor site during a 14-day treatment period. In addition, they showed almost no impairment to the body. The presently developed HES-SS-DOX@ICG NPs have good in vivo safety and highly efficient anti-tumor capability. These NPs in conjugation with laser irradiation have promising potential for chemo-photothermal cancer therapy in the clinic.
Episodic memory enables humans to encode and later vividly retrieve information about our rich experiences, yet the neural representations that support this mental capacity are poorly understood. Using a large fMRI dataset ( n = 468) of face-name associative memory tasks and principal component analysis to examine neural representational dimensionality (RD), we found that the human brain maintained a high-dimensional representation of faces through hierarchical representation within and beyond the face-selective regions. Critically, greater RD was associated with better subsequent memory performance both within and across participants, and this association was specific to episodic memory but not general cognitive abilities. Furthermore, the frontoparietal activities could suppress the shared low-dimensional fluctuations and reduce the correlations of local neural responses, resulting in greater RD. RD was not associated with the degree of item-specific pattern similarity, and it made complementary contributions to episodic memory. These results provide a mechanistic understanding of the role of RD in supporting accurate episodic memory.
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