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Longitudinal Changes in Hippocampal-Default Mode Network Connectivity and Cognition During Electroacupuncture Intervention in Type 2 Diabetes-Associated Cognitive Decline: A Pilot Resting-State fMRI Study.

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Title: Longitudinal Changes in Hippocampal-Default Mode Network Connectivity and Cognition During Electroacupuncture Intervention in Type 2 Diabetes-Associated Cognitive Decline: A Pilot Resting-State fMRI Study.
Authors: Yao L; Institute of Acupuncture and Massage, Northeast Asian Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, 130117 Changchun, Jilin, China., Li MY; Institute of Acupuncture and Massage, Northeast Asian Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, 130117 Changchun, Jilin, China., Liu YZ; Acupuncture and Tuina Center, The Third Affiliated Clinical Hospital of Changchun University of Chinese Medicine, 130117 Changchun, Jilin, China., Cao JZ; College of nursing, Changchun University of Chinese Medicine, 130117 Changchun, Jilin, China., Lian Z; College of Acupuncture and Massage, Changchun University of Chinese Medicine, 130117 Changchun, Jilin, China., Zhu HN; College of Acupuncture and Massage, Changchun University of Chinese Medicine, 130117 Changchun, Jilin, China., Huang HP; College of Acupuncture and Massage, Changchun University of Chinese Medicine, 130117 Changchun, Jilin, China., Zhong Z; College of Acupuncture and Massage, Changchun University of Chinese Medicine, 130117 Changchun, Jilin, China., Wang HF; College of Acupuncture and Massage, Changchun University of Chinese Medicine, 130117 Changchun, Jilin, China.
Source: Journal of integrative neuroscience [J Integr Neurosci] 2026 Sep 21; Vol. 25 (9), pp. 52929.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: IMR Press Country of Publication: Singapore NLM ID: 101156357 Publication Model: Print Cited Medium: Internet ISSN: 0219-6352 (Print) Linking ISSN: 02196352 NLM ISO Abbreviation: J Integr Neurosci Subsets: MEDLINE
Imprint Name(s): Publication: 2021-: Singapore : IMR Press
Original Publication: London : Imperial College Press, c2002-
MeSH Terms: Diabetes Mellitus, Type 2*/complications , Diabetes Mellitus, Type 2*/physiopathology , Diabetes Mellitus, Type 2*/diagnostic imaging , Hippocampus*/diagnostic imaging , Hippocampus*/physiopathology , Default Mode Network*/diagnostic imaging , Default Mode Network*/physiopathology , Cognitive Dysfunction*/etiology , Cognitive Dysfunction*/physiopathology , Cognitive Dysfunction*/diagnostic imaging , Cognitive Dysfunction*/therapy , Nerve Net*/diagnostic imaging , Nerve Net*/physiopathology , Electroacupuncture* , Connectome*, Humans ; Pilot Projects ; Magnetic Resonance Imaging ; Female ; Male ; Longitudinal Studies ; Middle Aged ; Aged ; Cognitive Enhancement
Abstract: Background: Type 2 diabetes mellitus-associated cognitive dysfunction (T2DACD) is strongly linked to disruption of cognition-supporting brain networks. Electroacupuncture (EA) has increasingly been examined as a nonpharmacological intervention targeting cognitive impairment; however, the longitudinal neurobiological patterns accompanying EA in T2DACD have not been fully characterized. In this exploratory pilot study, we evaluated alterations in resting-state functional connectivity (RSFC) across hippocampal subregions and default mode network (DMN) nodes in individuals with T2DACD.
Methods: For this exploratory, open-label, non-randomized, uncontrolled pilot investigation, we enrolled 20 individuals with T2DACD and 26 healthy controls (HCs). Longitudinal analyses included 15 participants who had usable post-treatment data. T2DACD was defined according to clinical type 2 diabetes mellitus criteria, and a Montreal Cognitive Assessment (MoCA) score <26. Patients underwent an 8-week Adjust Zang-fu and Arouse Spirit electroacupuncture (AZASE) intervention. Cognitive, emotional, metabolic, and seed-based resting-state functional magnetic resonance imaging (rs-fMRI) outcomes were evaluated. Clinical longitudinal analyses were carried out according to protocol, whereas imaging analyses were limited to participants with usable scans after treatment.
Results: At baseline, individuals with T2DACD showed lower MoCA scores than HCs and had poorer executive and working-memory outcomes. Among the 15 participants with complete longitudinal neuroimaging data, MoCA scores increased from 23.27 ± 1.71 to 26.07 ± 1.53 over the intervention period. Within-group alterations were observed for Flanker-conflict reaction time and accuracy, Stroop-conflict reaction time, 1-back reaction time, Self-Rating Anxiety Scale score, and Hamilton Depression Rating Scale score. Omnibus group analyses detected significant effects for the left anterior hippocampus-left angular gyrus connection and the left posterior hippocampus-right middle occipital gyrus connection. Post-treatment scans demonstrated reduced RSFC in several hippocampal-DMN and intra-DMN connections. The association between change in left anterior hippocampus-left angular gyrus RSFC and change in Stroop-conflict performance was no longer statistically significant after Bonferroni correction. For neuroimaging outcomes, cluster-level family-wise error (FWE) correction (p < 0.05) was applied to control for multiple comparisons; clinical outcomes are reported descriptively as hypothesis-generating findings.
Conclusions: In this exploratory pilot study, we identified preliminary alterations in cognitive outcomes and hippocampal-DMN connections over an 8-week EA intervention in individuals with T2DACD. In view of the small sample size and the open-label, non-randomized, uncontrolled design, the findings should be interpreted as hypothesis-generating observations rather than definitive evidence of a specific causal treatment effect. Larger controlled studies will be needed to determine whether the observed neural and behavioral alterations are reproducible and clinically meaningful in practice.
Clinical Trial Registration: No: ChiCTR2000040268, https://www.chictr.org.cn/hvshowproject.html?id=76145&v=1.3.
(Copyright: © 2026 The Author(s). Published by IMR Press.)
Competing Interests: The authors declare no conflicts of interest.
Grant Information: 82074548 National Natural Science Foundation of China; YDZJ202401680ZYTS Natural Science Foundation of Jilin Province (Free exploration of general projects)
Contributed Indexing: Keywords: cognitive dysfunction; default mode network; diabetes mellitus, type 2; electroacupuncture; hippocampus; magnetic resonance imaging
Entry Date(s): Date Created: 20260930 Date Completed: 20260930 Latest Revision: 20260930
Update Code: 20260930
DOI: 10.31083/JIN52929
PMID: 42811891
Database: MEDLINE
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  Data: Longitudinal Changes in Hippocampal-Default Mode Network Connectivity and Cognition During Electroacupuncture Intervention in Type 2 Diabetes-Associated Cognitive Decline: A Pilot Resting-State fMRI Study.
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  Data: &lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Yao+L%22&quot;&gt;Yao L&lt;/searchLink&gt;; Institute of Acupuncture and Massage, Northeast Asian Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, 130117 Changchun, Jilin, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Li+MY%22&quot;&gt;Li MY&lt;/searchLink&gt;; Institute of Acupuncture and Massage, Northeast Asian Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, 130117 Changchun, Jilin, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Liu+YZ%22&quot;&gt;Liu YZ&lt;/searchLink&gt;; Acupuncture and Tuina Center, The Third Affiliated Clinical Hospital of Changchun University of Chinese Medicine, 130117 Changchun, Jilin, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Cao+JZ%22&quot;&gt;Cao JZ&lt;/searchLink&gt;; College of nursing, Changchun University of Chinese Medicine, 130117 Changchun, Jilin, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Lian+Z%22&quot;&gt;Lian Z&lt;/searchLink&gt;; College of Acupuncture and Massage, Changchun University of Chinese Medicine, 130117 Changchun, Jilin, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Zhu+HN%22&quot;&gt;Zhu HN&lt;/searchLink&gt;; College of Acupuncture and Massage, Changchun University of Chinese Medicine, 130117 Changchun, Jilin, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Huang+HP%22&quot;&gt;Huang HP&lt;/searchLink&gt;; College of Acupuncture and Massage, Changchun University of Chinese Medicine, 130117 Changchun, Jilin, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Zhong+Z%22&quot;&gt;Zhong Z&lt;/searchLink&gt;; College of Acupuncture and Massage, Changchun University of Chinese Medicine, 130117 Changchun, Jilin, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Wang+HF%22&quot;&gt;Wang HF&lt;/searchLink&gt;; College of Acupuncture and Massage, Changchun University of Chinese Medicine, 130117 Changchun, Jilin, China.
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  Data: &lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Diabetes+Mellitus%2C+Type+2%22&quot;&gt;Diabetes Mellitus, Type 2*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Diabetes+Mellitus%2C+Type+2+complications%22&quot;&gt;complications&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Diabetes+Mellitus%2C+Type+2%22&quot;&gt;Diabetes Mellitus, Type 2*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Diabetes+Mellitus%2C+Type+2+physiopathology%22&quot;&gt;physiopathology&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Diabetes+Mellitus%2C+Type+2%22&quot;&gt;Diabetes Mellitus, Type 2*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Diabetes+Mellitus%2C+Type+2+diagnostic+imaging%22&quot;&gt;diagnostic imaging&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Hippocampus%22&quot;&gt;Hippocampus*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Hippocampus+diagnostic+imaging%22&quot;&gt;diagnostic imaging&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Hippocampus%22&quot;&gt;Hippocampus*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Hippocampus+physiopathology%22&quot;&gt;physiopathology&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Default+Mode+Network%22&quot;&gt;Default Mode Network*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Default+Mode+Network+diagnostic+imaging%22&quot;&gt;diagnostic imaging&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Default+Mode+Network%22&quot;&gt;Default Mode Network*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Default+Mode+Network+physiopathology%22&quot;&gt;physiopathology&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Cognitive+Dysfunction%22&quot;&gt;Cognitive Dysfunction*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Cognitive+Dysfunction+etiology%22&quot;&gt;etiology&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Cognitive+Dysfunction%22&quot;&gt;Cognitive Dysfunction*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Cognitive+Dysfunction+physiopathology%22&quot;&gt;physiopathology&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Cognitive+Dysfunction%22&quot;&gt;Cognitive Dysfunction*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Cognitive+Dysfunction+diagnostic+imaging%22&quot;&gt;diagnostic imaging&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Cognitive+Dysfunction%22&quot;&gt;Cognitive Dysfunction*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Cognitive+Dysfunction+therapy%22&quot;&gt;therapy&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Nerve+Net%22&quot;&gt;Nerve Net*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Nerve+Net+diagnostic+imaging%22&quot;&gt;diagnostic imaging&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Nerve+Net%22&quot;&gt;Nerve Net*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Nerve+Net+physiopathology%22&quot;&gt;physiopathology&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Electroacupuncture%22&quot;&gt;Electroacupuncture*&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Connectome%22&quot;&gt;Connectome*&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Humans%22&quot;&gt;Humans&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Pilot+Projects%22&quot;&gt;Pilot Projects&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Magnetic+Resonance+Imaging%22&quot;&gt;Magnetic Resonance Imaging&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Female%22&quot;&gt;Female&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Male%22&quot;&gt;Male&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Longitudinal+Studies%22&quot;&gt;Longitudinal Studies&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Middle+Aged%22&quot;&gt;Middle Aged&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Aged%22&quot;&gt;Aged&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Cognitive+Enhancement%22&quot;&gt;Cognitive Enhancement&lt;/searchLink&gt;
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  Group: Ab
  Data: Background: Type 2 diabetes mellitus-associated cognitive dysfunction (T2DACD) is strongly linked to disruption of cognition-supporting brain networks. Electroacupuncture (EA) has increasingly been examined as a nonpharmacological intervention targeting cognitive impairment; however, the longitudinal neurobiological patterns accompanying EA in T2DACD have not been fully characterized. In this exploratory pilot study, we evaluated alterations in resting-state functional connectivity (RSFC) across hippocampal subregions and default mode network (DMN) nodes in individuals with T2DACD.&lt;br /&gt;Methods: For this exploratory, open-label, non-randomized, uncontrolled pilot investigation, we enrolled 20 individuals with T2DACD and 26 healthy controls (HCs). Longitudinal analyses included 15 participants who had usable post-treatment data. T2DACD was defined according to clinical type 2 diabetes mellitus criteria, and a Montreal Cognitive Assessment (MoCA) score &amp;lt;26. Patients underwent an 8-week Adjust Zang-fu and Arouse Spirit electroacupuncture (AZASE) intervention. Cognitive, emotional, metabolic, and seed-based resting-state functional magnetic resonance imaging (rs-fMRI) outcomes were evaluated. Clinical longitudinal analyses were carried out according to protocol, whereas imaging analyses were limited to participants with usable scans after treatment.&lt;br /&gt;Results: At baseline, individuals with T2DACD showed lower MoCA scores than HCs and had poorer executive and working-memory outcomes. Among the 15 participants with complete longitudinal neuroimaging data, MoCA scores increased from 23.27 &#177; 1.71 to 26.07 &#177; 1.53 over the intervention period. Within-group alterations were observed for Flanker-conflict reaction time and accuracy, Stroop-conflict reaction time, 1-back reaction time, Self-Rating Anxiety Scale score, and Hamilton Depression Rating Scale score. Omnibus group analyses detected significant effects for the left anterior hippocampus-left angular gyrus connection and the left posterior hippocampus-right middle occipital gyrus connection. Post-treatment scans demonstrated reduced RSFC in several hippocampal-DMN and intra-DMN connections. The association between change in left anterior hippocampus-left angular gyrus RSFC and change in Stroop-conflict performance was no longer statistically significant after Bonferroni correction. For neuroimaging outcomes, cluster-level family-wise error (FWE) correction (p &amp;lt; 0.05) was applied to control for multiple comparisons; clinical outcomes are reported descriptively as hypothesis-generating findings.&lt;br /&gt;Conclusions: In this exploratory pilot study, we identified preliminary alterations in cognitive outcomes and hippocampal-DMN connections over an 8-week EA intervention in individuals with T2DACD. In view of the small sample size and the open-label, non-randomized, uncontrolled design, the findings should be interpreted as hypothesis-generating observations rather than definitive evidence of a specific causal treatment effect. Larger controlled studies will be needed to determine whether the observed neural and behavioral alterations are reproducible and clinically meaningful in practice.&lt;br /&gt;Clinical Trial Registration: No: ChiCTR2000040268, https://www.chictr.org.cn/hvshowproject.html?id=76145&amp;v=1.3.&lt;br /&gt; (Copyright: &#169; 2026 The Author(s). Published by IMR Press.)
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  Data: The authors declare no conflicts of interest.
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  Data: 82074548 National Natural Science Foundation of China; YDZJ202401680ZYTS Natural Science Foundation of Jilin Province (Free exploration of general projects)
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  Data: &lt;i&gt;Keywords: &lt;/i&gt;cognitive dysfunction; default mode network; diabetes mellitus, type 2; electroacupuncture; hippocampus; magnetic resonance imaging
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  Data: &lt;i&gt;Date Created: &lt;/i&gt;20260930 &lt;i&gt;Date Completed: &lt;/i&gt;20260930 &lt;i&gt;Latest Revision: &lt;/i&gt;20260930
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      – SubjectFull: Diabetes Mellitus, Type 2 complications
        Type: general
      – SubjectFull: Diabetes Mellitus, Type 2 physiopathology
        Type: general
      – SubjectFull: Diabetes Mellitus, Type 2 diagnostic imaging
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      – SubjectFull: Hippocampus diagnostic imaging
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      – TitleFull: Longitudinal Changes in Hippocampal-Default Mode Network Connectivity and Cognition During Electroacupuncture Intervention in Type 2 Diabetes-Associated Cognitive Decline: A Pilot Resting-State fMRI Study.
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            – D: 21
              M: 09
              Text: 2026 Sep 21
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