Brain state dynamics and working memory in patients with schizophrenia and unaffected siblings.

Publisher: BioMed Central Country of Publication: England NLM ID: 101190723 Publication Model: Electronic Cited Medium: Internet ISSN: 1741-7015 (Electronic) Linking ISSN: 17417015 NLM ISO Abbreviation: BMC Med Subsets: MEDLINE

Original Publication: [London] : BioMed Central, 2003-

Schizophrenia*/physiopathology ; Memory, Short-Term*/physiology ; Siblings*/psychology ; Brain*/physiopathology ; Brain*/diagnostic imaging; Humans ; Male ; Female ; Adult ; Magnetic Resonance Imaging ; Middle Aged ; Bayes Theorem ; Case-Control Studies ; Young Adult

Competing Interests: Declarations. Ethics approval and consent to participate: All participants were right-handed native Chinese speakers and signed written informed consent to participate in this study. The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2013. All procedures involving human participants were approved by the medical ethics committee of the Second Xiangya Hospital, Central South University, with the approval number as 2021015. Consent for publication: Not applicable. Competing interests: LP reports personal fees for serving as chief editor from the Canadian Medical Association Journals, speaker/consultant fee from Janssen Canada and Otsuka Canada, SPMM Course Limited, UK, Canadian Psychiatric Association; book royalties from Oxford University Press; investigator-initiated educational grants from Janssen Canada, Sunovion and Otsuka Canada outside the submitted work. All other authors report no potential conflicts.
Background: Working memory (WM) deficits are a key feature of schizophrenia and are also seen in unaffected siblings. These deficits might arise  from disrupted transitions from one brain state to another. Using a robust algorithm called the Bayesian Switching Dynamical System (BSDS), we studied hidden brain states and their transitions during a WM task in people with schizophrenia.
Methods: We used BSDS to identify brain states based on regions of interest (ROIs) within the default mode network and the frontoparietal network in 161 patients with schizophrenia, 37 unaffected siblings, and 96 healthy controls during N-back (0, 2, and resting fixation) tasks. We estimated group differences in the properties of brain states and studied the influence of WM performance and clinical characteristics on them using General Linear Models.
Results: We identified 4 brain states underlying the WM task: high-demand, low-demand, fixation, and non-dominant states. Compared with controls and siblings, patients showed reduced occupancy and lifetime of high-demand state during the "2-back," reduced lifetime of low-demand state during the "0-back," but increased occupancy and lifetime of fixation state during both task periods. Aberrant high-demand state mediated the association between WM performance and negative symptoms. Compared with controls and patients, siblings showed increased occupancy of high-demand and reduced fixation state during the resting fixation condition; this putative compensatory process correlated with better WM performance.
Conclusions: Latent brain states of intrinsic connectivity that represent internal mental processes affect WM performance, influencing the expression of negative symptoms in schizophrenia and cognitive resilience in unaffected siblings.
(© 2025. The Author(s).)

Trends Cogn Sci. 2011 Oct;15(10):483-506. (PMID: 21908230)
Netw Neurosci. 2020 Feb 01;4(1):30-69. (PMID: 32043043)
Hum Brain Mapp. 2020 Aug 1;41(11):2999-3008. (PMID: 32372508)
Front Neurosci. 2017 Mar 15;11:107. (PMID: 28360829)
Cogn Neuropsychiatry. 2013;18(1-2):44-82. (PMID: 22998599)
Cereb Cortex. 2023 May 24;33(11):7076-7087. (PMID: 36843051)
Cogn Affect Behav Neurosci. 2012 Jun;12(2):241-68. (PMID: 22282036)
Neuroimage. 2018 Oct 15;180(Pt B):646-656. (PMID: 28669905)
Front Cell Neurosci. 2022 Nov 08;16:1006797. (PMID: 36425664)
World Psychiatry. 2008 Feb;7(1):11-8. (PMID: 18458787)
J Am Acad Child Adolesc Psychiatry. 2012 Sep;51(9):911-20.e2. (PMID: 22917204)
Psychol Med. 2016 Apr;46(6):1211-24. (PMID: 26743997)
Asian J Psychiatr. 2024 Jul;97:104077. (PMID: 38781692)
Neuroimage Clin. 2020;28:102377. (PMID: 32805679)
Neuroinformatics. 2016 Jul;14(3):339-51. (PMID: 27075850)
Schizophr Bull. 2024 Jan 1;50(1):96-106. (PMID: 37018464)
Schizophr Bull. 2006 Jan;32(1):179-94. (PMID: 16166612)
Proc Natl Acad Sci U S A. 2016 Nov 1;113(44):12568-12573. (PMID: 27791105)
Eur Neuropsychopharmacol. 2014 Apr;24(4):545-52. (PMID: 24491950)
Proc Natl Acad Sci U S A. 2015 Sep 15;112(37):11678-83. (PMID: 26324898)
Neuropsychopharmacology. 2016 Aug;41(9):2411-20. (PMID: 27103065)
Neuroimage. 2016 Feb 1;126:81-95. (PMID: 26631815)
Annu Rev Psychol. 2015 Jan 3;66:115-42. (PMID: 25251486)
Schizophr Bull. 2015 Nov;41(6):1397-402. (PMID: 25841041)
Hum Brain Mapp. 2023 May;44(7):2873-2896. (PMID: 36852654)
Nat Commun. 2018 Jun 27;9(1):2505. (PMID: 29950686)
Annu Rev Clin Psychol. 2012;8:49-76. (PMID: 22224834)
Psychiatry Res. 2013 Nov 30;214(2):94-101. (PMID: 23993992)
Prog Neurobiol. 2022 Jan;208:102180. (PMID: 34627994)
Hum Brain Mapp. 2017 Jan;38(1):97-108. (PMID: 27534733)
J Psychiatry Neurosci. 2022 Sep 27;47(5):E341-E350. (PMID: 36167413)
Int J Neuropsychopharmacol. 2013 Jul;16(6):1195-204. (PMID: 23164479)
Nat Commun. 2021 Jun 9;12(1):3478. (PMID: 34108456)
J Neurosci. 2011 Jun 1;31(22):8259-70. (PMID: 21632947)
Behav Sci (Basel). 2013 Jun 27;3(3):330-347. (PMID: 25379242)
Mol Psychiatry. 2019 May;24(5):633-642. (PMID: 30242229)
Neuroimage. 2012 Jul 16;61(4):907-20. (PMID: 22484408)
Neuroimage. 2013 Oct 15;80:360-78. (PMID: 23707587)
Br J Psychiatry. 2025 Jan 07;:1-10. (PMID: 39763421)

82201663 National Natural Science Foundation of China; kq2306008 Training Program for Excellent Young Innovators of Changsha; B202303095947 Health Commission of Hunan Province; 2025JJ40077 Science and Technology Program of Hunan Province

Keywords: Cognitive deficits; Dynamic; Genetic; Markov; Psychosis

Date Created: 20250702 Date Completed: 20250702 Latest Revision: 20250704

20250704

PMC12220267

10.1186/s12916-025-04216-6

40598470