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Affective and cognitive theory of mind and associated brain functional alterations in frontotemporal dementia.

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  1. [1] § Materials and methods › MRI analysis › Connectome in FTD patients and age-matched HC ↔ Matrices_script_anonymized.m, lines 5–25 · score 0.62 · Negative correlation, Functional connections, masked, Fisher, ROIs, transformation

Paper

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The authors' code

MATLAB · 49 lines · 1.5 KB · no license · 1 match

  2. % CONNECTIVITY MATRICES POSTPROCESSING AND GRAPH ANALYSIS
  5. %% A) Matrices postprocessing
  7. % load concatenated matrices, i.e. functional connectivity data from multiple groups that have been stacked along the third dimension to form a single 3D array
  8. imported = load('/path/to/results/connectome_ALL_GROUPS.mat');
  9. connectivity = imported.connectome_ALL_GROUPS;
  10. subjects = imported.subjects;
  12. imported = load(''); % load mask of healthy controls
  13. mask = imported.mask;
  15. % Fisher transformation
  16. connectivity = fisherz(connectivity);
  18. % removal of negative correlations
  19. connectivity(connectivity < 0) = 0;
  21. % apply mask to the matrix
  22. inds = find(mask);
  23. inds_all = bsxfun(@plus, inds, N*N*[0:n-1]); %N refers to the number of ROIs
  24. connectivity(collapse(inds_all)) = 0;
  25. connectivity(connectivity == 0) = NaN;
  29. %% B) Network matrices creation
  31. % For each network, create a matrix containing the regions of the network
  32. % network1_regions should be defined as indices of regions in AAL atlas
  33. connectivity_network1 = connectivity(network1_regions, network1_regions, XX); % "XX" indicates subjects
  36. %% C) Graph measures extraction
  38. addpath /path/to/BrainNet_Viewer/ % generic path to BrainNet Viewer
  40. connectivity = connectivity_network1;
  42. for i=1:size(connectivity,3)
  43. i
  45. [BC(:,i), deg(:,i), str(:,i), C(:,i), C_tri(:,i), path(:,i), E_global(:,i), E_local(:,i)]= List_measures_for_hub(connectivity(:,:,i));
  48. end
  49. % Call the custom script 'List_measures_for_hub' to extract graph-theoretical measures for network nodes

Matrices_script_anonymized.m at commit 88f9899, no license · at the source

Overview

Authors: Chiara Tripodi1,2,3, Elisa Canu1,2, Anna Marangon1,3, Veronica Castelnovo1,2, Silvia Basaia1, Edoardo G Spinelli1,2,3, Giordano Cecchetti1,2, Alma Ghirelli1,2,3, Stefano Pisano1,2, Giulia Rugarli1,2,3, Francesca Caso2, Giuseppe Magnani2, Paola Caroppo4, Sara Prioni4, Cristina Villa4, Lucio Tremolizzo5, Ildebrando Appollonio5, Federico Verde6, Nicola Ticozzi6,7, Vincenzo Silani6,7, Massimo Filippi1,2,3,8,9, Federica Agosta1,2,3
ORCID iDs: Edoardo G Spinelli, Giordano Cecchetti, Alma Ghirelli, Sara Prioni, Nicola Ticozzi, Massimo Filippi, Federica Agosta
  1. Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy
  2. Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy
  3. Vita-Salute San Raffaele University, Milan 20132, Italy
  4. Fondazione IRCCS Istituto Neurologico Carlo Besta, Unit of Neurology 5—Neuropathology, Milan 20133, Italy
  5. Neurology Unit, ‘San Gerardo’ Hospital and University of Milano-Bicocca, Monza 20900, Italy
  6. Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan 20149, Italy
  7. ‘Dino Ferrari’ Center, Department of Pathophysiology and Transplantation, Università Degli Studi di Milano, Milan 20122, Italy
  8. Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy
  9. Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy
Institutions: Vita-Salute San Raffaele University (Italy); IRCCS Ospedale San Raffaele (Italy); Fondazione IRCCS Istituto Neurologico Carlo Besta (Italy); Azienda Ospedaliera San Gerardo (Italy); University of Milano-Bicocca (Italy); IRCCS Istituto Auxologico Italiano (Italy); University of Milan (Italy)
Journal: Brain communications, volume 8, issue 3, article fcag216
Dates: received 15 December 2025; accepted 6 May 2026; published online 6 June 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1093/braincomms/fcag216 · PMID 42311451 · PMCID PMC13270490 · OpenAlex W7163753785
Open access: gold, a free copy (OpenAlex)
Status: code verified
Categories: fMRI (modality), human (organism), Alzheimer's / dementia (population)
Methods: Statistics, Smoothing, state filtering, decompositions, Preprocessing, Connectivity, Graphs, fMRI & imaging
Keywords: social cognition, theory of mind (ToM), frontotemporal dementia (FTD), functional connectivity
Topic: Functional Brain Connectivity Studies (Cognitive Neuroscience, Neuroscience), according to OpenAlex
Funding: European Research Council (StG-2016_714388)
Citations: not cited yet (Europe PMC); 59 references in the paper

Abstract

Theory of mind (ToM), the ability to infer others’ beliefs (cognitive ToM) and emotions (affective ToM), is compromised in behavioural variant frontotemporal dementia (bvFTD). However, its diagnostic and prognostic value in other frontotemporal dementia (FTD) variants remains underexplored due to limited understanding of the underlying neural mechanisms. This study investigated whether ToM deficits are shared across the frontotemporal dementia spectrum and explored the functional connectivity alterations underlying these disturbances using resting-state functional magnetic resonance imaging. Sixty-seven FTD patients [14 non-fluent variant primary progressive aphasia (nfvPPA), 17 semantic variant primary progressive aphasia (svPPA), 23 bvFTD, 13 right temporal variant frontotemporal dementia (rtvFTD); 34 women; mean age 66.5 ± 7.7 years] and two control groups (48 age-matched healthy controls; 50 young healthy controls) underwent clinical, neuropsychological and brain magnetic resonance imaging assessments. ToM was evaluated in patients using the Story-Based Empathy Task (SET), which includes the Story-Based Empathy Task affective subtest (SET-EA) and the Story-Based Empathy Task cognitive subtest (SET-IA). Resting-state functional connectivity networks were obtained in young healthy controls using seed-based analysis centred on the left medial prefrontal cortex for affective ToM and the right supramarginal gyrus for cognitive ToM. In addition, four large-scale functional networks were reconstructed to reflect disease-specific vulnerability. Functional brain connectivity within all networks was quantified using graph analysis and connectomics, and between-group comparisons were performed on both global and seed-based regional metrics. All patient groups showed similar impairments in affective and cognitive ToM performance. Network analyses revealed two dissociable but interconnected ToM systems. Global metrics of network topology indicated increased path length and reduced nodal strength in both ToM networks, particularly in bvFTD and nfvPPA patients (P < 0.05). Direct seed-based connectivity analyses confirmed widespread functional connectivity reductions from key nodes (e.g. left inferior frontal gyrus, anterior cingulate cortex) in these groups. In contrast, svPPA and rtvFTD cases exhibited relatively preserved functional connectivity within ToM circuits. Correlation analyses revealed associations between cognitive ToM network metrics and global ToM performance, and between functional connectivity in the salience network and behavioural dysfunction. Affective and cognitive ToM abilities are comparably impaired across FTD variants, suggesting that socio-cognitive impairments may represent a core and early feature across the FTD spectrum. Such deficits are mirrored by patterns of functional disconnection within dedicated large-scale networks, with bvFTD and nfvPPA showing the most pronounced disruptions. This study underscores the diagnostic relevance of socio-cognitive markers and highlights their potential as clinical and biomarker targets in future therapeutic interventions.

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

Repository

Its files are read in the Code ↔ Paper reader above, with 1 match between paragraphs and lines of code.

SilviaBasaia/Theory-of-mind-in-frontotemporal-dementia

License: none: the authors keep all their rights
State: the link answers, verified on 27 September 2026
Evidence: files inventoried
Commit: 88f989940cb01cdbcb9dc2cc8c16a30d9ea4156e, 31 March 2026
Languages: MATLAB (3)
Size: 4 files, 3 scripts
Software Heritage: not archived
Found in: “Data availability”
Holds: README
Not found: license file, CITATION.cff, environment file, tests, continuous integration, documentation
Tools: Statistics and Machine Learning Toolbox (2 files)
Availability: 1 check, the latest on 27 September 2026: the link answers
  • 27 September 2026: the link answers
4 files
At the source: github.com/SilviaBasaia/Theory-of-mind-in-frontotemporal-dementia

The paper's code and data availability statement is in the Data section.

Tracing map

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  • 3 scripts, each with its path and the digest of its content;
  • 1 match between paragraphs of the paper and lines of the code (method lexical-v1);
  • neither the text of the paper nor the code itself.

Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.

Data

No dataset and no data link were found in the paper.

Data availability

The anonymized dataset used and analysed during the current study will be made available by the corresponding author upon request to qualified researchers (i.e. affiliated to a university or research institution/hospital). Seed-based analyses were conducted using standard tools implemented in FSL. For the connectomics analysis, the codes that support the findings of this study are openly available in GitHub public repository at https://github.com/SilviaBasaia/Theory-of-mind-in-frontotemporal-dementia (https://github.com/SilviaBasaia/Theory-of-mind-in-frontotemporal-dementia).

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

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 22 authors, 4 keywords, 1 funder, 58 references.

Cite

This paper

Tripodi, C., Canu, E., Marangon, A., Castelnovo, V., Basaia, S., Spinelli, E. G., Cecchetti, G., Ghirelli, A., Pisano, S., Rugarli, G., Caso, F., Magnani, G., Caroppo, P., Prioni, S., Villa, C., Tremolizzo, L., Appollonio, I., Verde, F., Ticozzi, N., . . . Agosta, F. (2026). Affective and cognitive theory of mind and associated brain functional alterations in frontotemporal dementia. Brain communications, 8(3), fcag216. https://doi.org/10.1093/braincomms/fcag216

BibTeX

@article{tripodi2026affective,
author = {Tripodi, Chiara and Canu, Elisa and Marangon, Anna and Castelnovo, Veronica and Basaia, Silvia and Spinelli, Edoardo G and Cecchetti, Giordano and Ghirelli, Alma and Pisano, Stefano and Rugarli, Giulia and Caso, Francesca and Magnani, Giuseppe and Caroppo, Paola and Prioni, Sara and Villa, Cristina and Tremolizzo, Lucio and Appollonio, Ildebrando and Verde, Federico and Ticozzi, Nicola and Silani, Vincenzo and Filippi, Massimo and Agosta, Federica},
title = {{Affective and cognitive theory of mind and associated brain functional alterations in frontotemporal dementia}},
journal = {Brain communications},
year = {2026},
month = jun,
volume = {8},
number = {3},
pages = {fcag216},
publisher = {Oxford University Press},
issn = {2632-1297},
doi = {10.1093/braincomms/fcag216},
url = {https://doi.org/10.1093/braincomms/fcag216},
pmid = {42311451},
pmcid = {PMC13270490}
}

RIS

TY - JOUR
AU - Tripodi, Chiara
AU - Canu, Elisa
AU - Marangon, Anna
AU - Castelnovo, Veronica
AU - Basaia, Silvia
AU - Spinelli, Edoardo G
AU - Cecchetti, Giordano
AU - Ghirelli, Alma
AU - Pisano, Stefano
AU - Rugarli, Giulia
AU - Caso, Francesca
AU - Magnani, Giuseppe
AU - Caroppo, Paola
AU - Prioni, Sara
AU - Villa, Cristina
AU - Tremolizzo, Lucio
AU - Appollonio, Ildebrando
AU - Verde, Federico
AU - Ticozzi, Nicola
AU - Silani, Vincenzo
AU - Filippi, Massimo
AU - Agosta, Federica
TI - Affective and cognitive theory of mind and associated brain functional alterations in frontotemporal dementia
T2 - Brain communications
J2 - Brain Commun
PY - 2026
DA - 2026/06/06
VL - 8
IS - 3
SP - fcag216
SN - 2632-1297
PB - Oxford University Press
DO - 10.1093/braincomms/fcag216
UR - https://doi.org/10.1093/braincomms/fcag216
LA - en
ER -

CSL-JSON

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