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Targeting insulo-frontal pathway to reduce stress-evoked cognitive rigidity.

Code ↔ Paper

5 matches between paragraphs of the paper and lines of its authors' code, computed by the harvester (lexical-v1). Click a colored paragraph or line to see its counterpart.

The 5 matches · all tie a paragraph to a whole file, not to given lines: weak matches, whose lines are not tinted
  1. [1] § Methods › Miniscope Ca imaging with optogenetic manipulation ↔ findResponsiveNeuron/ROCanalysis.m, the whole file · a weak match · score 0.64 · auROC, behavioral event, variable, inhibited, neuron, window
  2. [2] § Methods › Fiber photometry Ca recording ↔ convergence/periEventSigArray.m, the whole file · a weak match · score 0.61 · frame rate, behavioral events, field, duration, window, dig
  3. [3] § Results › The aIC → mPFC neurons carry outcome information ↔ findResponsiveNeuron/periEventSigArray.m, the whole file · a weak match · score 0.56 · peri event, Behavioral events, eat, calcium, reward, neurons
  4. [4] § Results › The aIC → mPFC neurons carry outcome information ↔ convergence/periEventSigArray.m, the whole file · a weak match · score 0.56 · peri event, Behavioral events, eat, calcium, reward, dig
  5. [5] § Methods › Fiber photometry Ca recording ↔ findResponsiveNeuron/periEventSigArray.m, the whole file · a weak match · score 0.54 · frame rate, behavioral events, duration, neurons, window, dig

Paper

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The authors' code

MATLAB · 127 lines · 4.6 KB · MIT · 2 matches

  1. function sigArray = periEventSigArray(dn,behEvtTbls)
  2. % This functions organizes ca signals into an periEvent array
  3. % Inputs:
  4. % dn: ca signal structure
  5. % .ca: calcium signal matrix: nFrame x nCell
  6. % .time: timestamps of each frame
  7. % .sttFrameT: table for the start time of each session of interest
  8. % behEvtTbls: structure with session name as field
  9. % behavior event table: nEvent x nFeature
  10. % Outputs:
  11. % sigArray: a structure with subfields for signals and metadata
  12. % .caA: calcium signals arranged in a 4d array
  13. % .Events: structure for behavior variables and event times organized by trial
  14. % .dimension = {'neuron','framePerWindow','eventWindow','trial'};
  15. %% organize multi-session signals
  16. sessionNames = fieldnames(behEvtTbls);
  17. nSession = length(sessionNames);
  18. %% extract ca signals corresponding to sessions
  19. % find the row (frame) index for the start of each session
  20. sessionStartIdx = zeros(nSession,1);
  21. for k = 1:nSession
  22. rowIdx = strcmp(dn.sttFrameT.session,sessionNames{k});
  23. sessionStartIdx(k) = find(dn.time==dn.sttFrameT.sttT(rowIdx));
  24. end
  25. sig = dn.ca(sessionStartIdx(1):end,:);
  26. time = dn.time(sessionStartIdx(1):end); % in sec
  27. fps = 1./diff(time(1:2)); % calcium frame rate ~10 Hz
  28. %% excluding start transients
  29. [~,nNeuron] = size(sig);
  30. % mask recording start caused transients in ca signal
  31. maskWin = round(3*fps); % 3 sec mask
  32. sigM = mean(sig,2);
  33. movieStartIdx = find(sigM == 0); % movie starts have 0 intensity
  34. transientFrame = movieStartIdx + (0:maskWin); % nStart x nWin
  35. transientFrame = transientFrame(:); % linearize
  36. sigN = sig;
  37. sigN(transientFrame,:) = NaN;
  38. sigN(sigN<0) = 0; % negative numbers are small and related to start transient in CNMFe
  39. % fill NaN in sigN by interpolation
  40. nanId = isnan(sigN(:,1));
  41. sigN = interp1(time(~nanId),sigN(~nanId,:),time);
  42. %% peri-event time windows
  43. tau = 2; %2 sec
  44. tWin = round(tau*fps);
  45. %% behavior variables to decode by trials: current and prior reward
  46. % event markers in behEvtTbls
  47. markerName = {'TrialStart','Approach','Dig','Outcome'};
  48. nMarker = length(markerName);
  49. % structures for behavior event times and labels, organized by trial
  50. EvtFrame = struct;
  51. TrialLabel = struct;
  52. counter = 1;
  53. for k = 1:nSession
  54. % single session behavior event table
  55. behEvtTbl = behEvtTbls.(sessionNames{k});
  56. uniqueTrials = unique(behEvtTbl.Trial);
  57. nTrial = length(uniqueTrials);
  58. % event index
  59. evtIdx = [];
  60. evtIdx.TrialStart = contains(behEvtTbl.Behavior,'TrialStart');
  61. evtIdx.Approach = contains(behEvtTbl.Behavior,'Approach');
  62. evtIdx.Dig = contains(behEvtTbl.Behavior,'Dig') & contains(behEvtTbl.Status,'START');
  63. evtIdx.Outcome = contains(behEvtTbl.Behavior,'Dig') & contains(behEvtTbl.Status,'STOP');
  64. for i = 1:nTrial
  65. trialIdx = behEvtTbl.Trial == uniqueTrials(i);
  66. if any(trialIdx & evtIdx.Dig) % exclude no dig (decision) trial
  67. % calculate event frames in ca movies
  68. for j = 1:nMarker
  69. markerIdx = trialIdx & evtIdx.(markerName{j});
  70. markerIdx = find(markerIdx,1,'last'); % keep last approach
  71. markerFrame = behEvtTbl.caFrame(markerIdx);
  72. EvtFrame.(markerName{j})(counter,1) = markerFrame;
  73. end
  74. TrialLabel.CurrRwd(counter,1) = any(contains(behEvtTbl.Behavior(trialIdx),'Eat'));
  75. TrialLabel.Trial(counter,1) = i;
  76. TrialLabel.Session(counter,1) = sessionNames(k);
  77. counter = counter+1;
  78. end
  79. end
  80. end
  81. TrialLabel.PriorRwd = [true;TrialLabel.CurrRwd(1:end-1)]; % first trial, true for prior reward
  82. %% calcium activity organized by nNeuron x tWin x nWin x nTrial
  83. winName = {'preSta','posSta','preApp','posApp','preDec','posDec','preOut','posOut'};
  84. nWin = length(winName);
  85. totalTrial = length(TrialLabel.Trial);
  86. caA = zeros(nNeuron,tWin,nWin,totalTrial); % ca signal array
  87. for i = 1:totalTrial
  88. for j = 1:nMarker
  89. caFrame = EvtFrame.(markerName{j})(i);
  90. caA(:,:,2*j-1,i) = sigN(caFrame-tWin : caFrame-1,:)';
  91. caA(:,:,2*j,i) = sigN(caFrame : caFrame+tWin-1,:)';
  92. end
  93. end
  94. % interpolate caA to 10Hz
  95. xq = linspace(1,tWin,round(tau*10));
  96. tWinIn = length(xq);
  97. caL = reshape(permute(caA,[2 1 3 4]),tWin,nNeuron*nWin*totalTrial);
  98. caL = interp1(1:tWin,caL,xq);
  99. caA = permute(reshape(caL,[tWinIn nNeuron nWin totalTrial]),[2 1 3 4]); % [nNeuron,tWin,nWin,nTrial]
  100. %% output structure
  101. sigArray.caA = caA;
  102. sigArray.dimension = {'neuron','framePerWindow','eventWindow','trial'};
  103. sigArray.TrialLabel = TrialLabel;
  104. sigArray.winName = winName;
  105. sigArray.winDurationSec = tau;
  106. sigArray.fpsOrigin = fps;
  107. sigArray.fps = 10;
  108. end

periEventSigArray.m at commit 843e8d0, under MIT · at the source

Overview

  1. Department of Molecular, Cell and Developmental Biology, University of California Santa Cruz,Santa Cruz, CA USA
  2. Department of Neuroscience, University of Rochester Medical Center,Rochester, NY USA
Institutions: University of California, Santa Cruz (United States); University of Rochester Medicine (United States)
Journal: Nature communications, volume 17, issue 1, article 5791
Dates: received 9 March 2026; accepted 7 April 2026; published online 27 April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41467-026-72221-1 · PMID 42045196 · PMCID PMC13332065 · OpenAlex W7155882386
Open access: gold, a free copy (OpenAlex)
Status: code verified
Categories: mouse (organism)
Methods: Statistics, Smoothing, state filtering, decompositions, Preprocessing, Evoked potentials, Connectivity, Machine learning, fMRI & imaging
Keywords: Neural circuits, Stress and resilience
MeSH: Cerebral Cortex*, Cognition*, Prefrontal Cortex*, Stress, Psychological*, Animals, Attention, Cognitive Enhancement, Cognitive Flexibility, Decision Making, Male, Mice, Mice, Inbred C57BL, Neural Pathways, Neurons, Optogenetics (* major topic)
Topic: Stress Responses and Cortisol (Behavioral Neuroscience, Neuroscience), according to OpenAlex
Funding: National Institute of Mental Health (R01MH127737, R01MH136381); National Institute on Aging (R01AG071787, U24AG072701); Max Planck Society (fellowship)
Citations: not cited yet (Europe PMC); 59 references in the paper

Abstract

Cognitive rigidity often follows chronic stress and is prevalent in stress-related psychiatric disorders, yet the underlying neural circuit mechanisms remain unclear. Using attentional set-shifting tasks (AST) in mice, we identified projection from the anterior insular cortex to the medial prefrontal cortex (aIC→mPFC) as key regulators of adaptive decision-making. The aIC→mPFC neurons show heightened activity following incorrect, but not correct, trials. This elevated activity persists into subsequent trials, providing a salience signal that enhances mPFC outcome-dependent updating and promotes convergence of neural activity patterns across trials. Optogenetic manipulation of aIC→mPFC projections during the pre-decision phase disrupts mPFC updating and impairs AST performance. Moreover, chronic stress disrupts the outcome-dependence of aIC activity and impairs cognitive flexibility. Crucially, selectively reinforcing aIC→mPFC activity after incorrect trials via optogenetics enhances mPFC updating, improves neural activity convergence across trials, and restores cognitive flexibility in stressed mice. These findings revealed a previously unrecognized role of the aIC→mPFC circuit in linking trial outcomes to adaptive decision-making and identified this pathway as a promising target for treating stress-induced cognitive rigidity.

Reproduced under the paper's license (CC BY), from the paper cited above.

Repository

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ZuoLabUCSC/Targeting-insulo-frontal-pathway-to-reduce-stress-evoked-cognitive-rigidity

License: MIT
State: the link answers, verified on 30 September 2026
Evidence: files inventoried
Commit: 843e8d01c2273bb10213a8f45a2b51aa6adf58da, 19 March 2026
Languages: MATLAB (8)
Size: 20 files, 8 scripts
Software Heritage: not archived
Found in: “Code availability”
Holds: README, license file
Not found: CITATION.cff, environment file, tests, continuous integration, documentation
Availability: 1 check, the latest on 30 September 2026: the link answers
  • 30 September 2026: the link answers
10 files

Code availability

All custom code used in this study is available at https://github.com/ZuoLabUCSC/Targeting-insulo-frontal-pathway-to-reduce-stress-evoked-cognitive-rigidity.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

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Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 3 authors, 2 keywords, 15 MeSH terms, 3 funders, 58 references.

Cite

This paper

Ma, S., Wang, K. H., & Zuo, Y. (2026). Targeting insulo-frontal pathway to reduce stress-evoked cognitive rigidity. Nature communications, 17(1), 5791. https://doi.org/10.1038/s41467-026-72221-1

BibTeX

@article{ma2026targeting,
author = {Ma, Shaorong and Wang, Kuan Hong and Zuo, Yi},
title = {{Targeting insulo-frontal pathway to reduce stress-evoked cognitive rigidity}},
journal = {Nature communications},
year = {2026},
month = apr,
volume = {17},
number = {1},
pages = {5791},
publisher = {Nature Publishing Group},
issn = {2041-1723},
doi = {10.1038/s41467-026-72221-1},
url = {https://doi.org/10.1038/s41467-026-72221-1},
pmid = {42045196},
pmcid = {PMC13332065}
}

RIS

TY - JOUR
AU - Ma, Shaorong
AU - Wang, Kuan Hong
AU - Zuo, Yi
TI - Targeting insulo-frontal pathway to reduce stress-evoked cognitive rigidity
T2 - Nature communications
J2 - Nat Commun
PY - 2026
DA - 2026/04/27
VL - 17
IS - 1
SP - 5791
SN - 2041-1723
PB - Nature Publishing Group
DO - 10.1038/s41467-026-72221-1
UR - https://doi.org/10.1038/s41467-026-72221-1
LA - en
ER -

CSL-JSON

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"PMCID": "PMC13332065",
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