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A working feedback-based framework for goal-directed spatial memory deficits in Alzheimer's disease: Feedforward and feedback interactions along the RSC-MEC-CA1-RSC axis.

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Τίτλος: A working feedback-based framework for goal-directed spatial memory deficits in Alzheimer's disease: Feedforward and feedback interactions along the RSC-MEC-CA1-RSC axis.
Συγγραφείς: Tian Y; School of Life Science, Beijing Institute of Technology, Beijing, PR China., Qing H; Department of Biology, Shenzhen SMU-BIT University, Longgang, Shenzhen, PR China., Quan Z; School of Life Science, Beijing Institute of Technology, Beijing, PR China.
Πηγή: Journal of Alzheimer's disease : JAD [J Alzheimers Dis] 2026 Oct; Vol. 113 (3), pp. 1002-1019. Date of Electronic Publication: 2026 Aug 08.
Τύπος έκδοσης: Journal Article; Review
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: SAGE Publications Country of Publication: United States NLM ID: 9814863 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1875-8908 (Electronic) Linking ISSN: 13872877 NLM ISO Abbreviation: J Alzheimers Dis Subsets: MEDLINE
Imprint Name(s): Publication: 2024- : [Thousand Oaks, CA] : SAGE Publications
Original Publication: Amsterdam ; Washington : IOS Press, c1998-
Ιατρικοί όροι (MeSH): Alzheimer Disease*/physiopathology , Alzheimer Disease*/complications , Alzheimer Disease*/psychology , Entorhinal Cortex*/physiopathology , Spatial Memory*/physiology , Memory Disorders*/physiopathology , Memory Disorders*/etiology , CA1 Region, Hippocampal*/physiopathology , Goals*, Neural Pathways/physiopathology ; Humans ; Animals
Περίληψη: Spatial navigation deficits are among the earliest and most clinically significant cognitive impairments in Alzheimer's disease (AD), particularly when navigation depends on goal-directed spatial memory. This review defines goal-directed spatial memory as a task-oriented construct and proposes a network-level framework for interpreting early AD navigation deficits. We synthesize anatomical, physiological, behavioral, and disease-related evidence concerning the retrosplenial cortex (RSC), medial entorhinal cortex (MEC), hippocampal CA1, and CA1-RSC feedback interactions. We propose the RSC-MEC-CA1-RSC axis as a testable working framework based on coordinated feedforward and feedback interactions. Within this system, the RSC integrates behaviorally relevant external cues and supports reference-frame transformation. The MEC contributes to path integration and self-goal relational coding, and CA1 consolidates these signals into functional goal-location representations. These representations can be retrieved, stabilized, and then transmitted back to cortical networks to guide continuous behavioral updating. Notably, we define the CA1-RSC pathway as a functional feedback route that supports iterative information updating, route correction and strategic adjustment. We argue that AD navigation deficits stem from the progressive breakdown of feedforward and feedback interactions across this axis, rather than from isolated dysfunction of single brain regions. The RSC-MEC-CA1-RSC framework offers a circuit-level mechanistic account for spatial disorientation in early AD. As a working model instead of a fully validated canonical circuit, it puts forward a series of testable hypotheses for future research, including cross-regional electrophysiological recordings, projection-specific circuit manipulation, imaging assessments, and differentiated navigation paradigms to examine cue use, path integration, goal retrieval and feedback-dependent updating.
Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Contributed Indexing: Keywords: Alzheimer's disease; feedback framework; goal-directed spatial memory; hippocampal CA1; medial entorhinal cortex; retrosplenial cortex
Entry Date(s): Date Created: 20260808 Date Completed: 20260929 Latest Revision: 20260929
Update Code: 20260929
DOI: 10.1177/13872877261473933
PMID: 42570289
Βάση Δεδομένων: MEDLINE
FullText Text:
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DbLabel: MEDLINE
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PubType: Academic Journal
PubTypeId: academicJournal
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  Data: A working feedback-based framework for goal-directed spatial memory deficits in Alzheimer's disease: Feedforward and feedback interactions along the RSC-MEC-CA1-RSC axis.
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  Data: <searchLink fieldCode="AU" term="%22Tian+Y%22">Tian Y</searchLink>; School of Life Science, Beijing Institute of Technology, Beijing, PR China.<br /><searchLink fieldCode="AU" term="%22Qing+H%22">Qing H</searchLink>; Department of Biology, Shenzhen SMU-BIT University, Longgang, Shenzhen, PR China.<br /><searchLink fieldCode="AU" term="%22Quan+Z%22">Quan Z</searchLink>; School of Life Science, Beijing Institute of Technology, Beijing, PR China.
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  Data: <searchLink fieldCode="JN" term="%229814863%22">Journal of Alzheimer's disease : JAD</searchLink> [J Alzheimers Dis] 2026 Oct; Vol. 113 (3), pp. 1002-1019. <i>Date of Electronic Publication: </i>2026 Aug 08.
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  Data: Journal Article; Review
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  Data: <i>Publication</i>: 2024- : [Thousand Oaks, CA] : SAGE Publications<br /><i>Original Publication</i>: Amsterdam ; Washington : IOS Press, c1998-
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  Data: <searchLink fieldCode="MM" term="%22Alzheimer+Disease%22">Alzheimer Disease*</searchLink>/<searchLink fieldCode="MM" term="%22Alzheimer+Disease+physiopathology%22">physiopathology</searchLink> <br /><searchLink fieldCode="MM" term="%22Alzheimer+Disease%22">Alzheimer Disease*</searchLink>/<searchLink fieldCode="MM" term="%22Alzheimer+Disease+complications%22">complications</searchLink> <br /><searchLink fieldCode="MM" term="%22Alzheimer+Disease%22">Alzheimer Disease*</searchLink>/<searchLink fieldCode="MM" term="%22Alzheimer+Disease+psychology%22">psychology</searchLink> <br /><searchLink fieldCode="MM" term="%22Entorhinal+Cortex%22">Entorhinal Cortex*</searchLink>/<searchLink fieldCode="MM" term="%22Entorhinal+Cortex+physiopathology%22">physiopathology</searchLink> <br /><searchLink fieldCode="MM" term="%22Spatial+Memory%22">Spatial Memory*</searchLink>/<searchLink fieldCode="MM" term="%22Spatial+Memory+physiology%22">physiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Memory+Disorders%22">Memory Disorders*</searchLink>/<searchLink fieldCode="MM" term="%22Memory+Disorders+physiopathology%22">physiopathology</searchLink> <br /><searchLink fieldCode="MM" term="%22Memory+Disorders%22">Memory Disorders*</searchLink>/<searchLink fieldCode="MM" term="%22Memory+Disorders+etiology%22">etiology</searchLink> <br /><searchLink fieldCode="MM" term="%22CA1+Region%2C+Hippocampal%22">CA1 Region, Hippocampal*</searchLink>/<searchLink fieldCode="MM" term="%22CA1+Region%2C+Hippocampal+physiopathology%22">physiopathology</searchLink> <br /><searchLink fieldCode="MM" term="%22Goals%22">Goals*</searchLink><br /><searchLink fieldCode="MH" term="%22Neural+Pathways%22">Neural Pathways</searchLink>/<searchLink fieldCode="MH" term="%22Neural+Pathways+physiopathology%22">physiopathology</searchLink> ; <searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Spatial navigation deficits are among the earliest and most clinically significant cognitive impairments in Alzheimer's disease (AD), particularly when navigation depends on goal-directed spatial memory. This review defines goal-directed spatial memory as a task-oriented construct and proposes a network-level framework for interpreting early AD navigation deficits. We synthesize anatomical, physiological, behavioral, and disease-related evidence concerning the retrosplenial cortex (RSC), medial entorhinal cortex (MEC), hippocampal CA1, and CA1-RSC feedback interactions. We propose the RSC-MEC-CA1-RSC axis as a testable working framework based on coordinated feedforward and feedback interactions. Within this system, the RSC integrates behaviorally relevant external cues and supports reference-frame transformation. The MEC contributes to path integration and self-goal relational coding, and CA1 consolidates these signals into functional goal-location representations. These representations can be retrieved, stabilized, and then transmitted back to cortical networks to guide continuous behavioral updating. Notably, we define the CA1-RSC pathway as a functional feedback route that supports iterative information updating, route correction and strategic adjustment. We argue that AD navigation deficits stem from the progressive breakdown of feedforward and feedback interactions across this axis, rather than from isolated dysfunction of single brain regions. The RSC-MEC-CA1-RSC framework offers a circuit-level mechanistic account for spatial disorientation in early AD. As a working model instead of a fully validated canonical circuit, it puts forward a series of testable hypotheses for future research, including cross-regional electrophysiological recordings, projection-specific circuit manipulation, imaging assessments, and differentiated navigation paradigms to examine cue use, path integration, goal retrieval and feedback-dependent updating.
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  Data: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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  Data: <i>Keywords: </i>Alzheimer's disease; feedback framework; goal-directed spatial memory; hippocampal CA1; medial entorhinal cortex; retrosplenial cortex
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  Data: <i>Date Created: </i>20260808 <i>Date Completed: </i>20260929 <i>Latest Revision: </i>20260929
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  Data: 10.1177/13872877261473933
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  Data: 42570289
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=42570289
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1177/13872877261473933
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        StartPage: 1002
    Subjects:
      – SubjectFull: Neural Pathways physiopathology
        Type: general
      – SubjectFull: Humans
        Type: general
      – SubjectFull: Animals
        Type: general
      – SubjectFull: Alzheimer Disease physiopathology
        Type: general
      – SubjectFull: Alzheimer Disease complications
        Type: general
      – SubjectFull: Alzheimer Disease psychology
        Type: general
      – SubjectFull: Entorhinal Cortex physiopathology
        Type: general
      – SubjectFull: Spatial Memory physiology
        Type: general
      – SubjectFull: Memory Disorders physiopathology
        Type: general
      – SubjectFull: Memory Disorders etiology
        Type: general
      – SubjectFull: CA1 Region, Hippocampal physiopathology
        Type: general
      – SubjectFull: Goals
        Type: general
    Titles:
      – TitleFull: A working feedback-based framework for goal-directed spatial memory deficits in Alzheimer's disease: Feedforward and feedback interactions along the RSC-MEC-CA1-RSC axis.
        Type: main
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          Name:
            NameFull: Tian Y
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          Name:
            NameFull: Qing H
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            – D: 01
              M: 10
              Text: 2026 Oct
              Type: published
              Y: 2026
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              Value: 113
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            – TitleFull: Journal of Alzheimer's disease : JAD
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