The subcortical default mode network and its alteration in Alzheimer's disease
Poster No:
1755
Submission Type:
Abstract Submission
Authors:
Sara Lozano Seoane1, Martijn van den Heuvel1, Ángel Acebes2, Niels Janssen2
Institutions:
1Vrije Universiteit Amsterdam, Amsterdam, the Netherlands, 2Universidad de La Laguna, Santa Cruz de Tenerife, Spain
First Author:
Co-Author(s):
Introduction:
The default mode network (DMN) is a central brain network to cognitive function (Raichle, 2001) and is suggested to play a major role in several disorders and to be particularly vulnerable to the neuropathological hallmarks of Alzheimer's disease (AD; Aggleton, 2016). While the cortical components of the DMN are well-established, the involvement of subcortical regions has received less attention in research, with findings showing variability across the literature (Aguilar, 2022; Alves, 2019; Choi, 2012; Li, 2021). Given the critical role of subcortical structures (such as the thalamus and amygdala) in AD pathology, understanding their functional integration within the DMN is essential (Aggleton, 2016; Stouffer, 2024; Yao, 2013). While subcortical regions have often been excluded in prior studies due to data limitations, their role in the default mode network and their changes in Alzheimer's disease present a promising area for deeper exploration.
Methods:
Here we performed a systematic review, meta-analysis and empirical validation of the subcortical default mode network in healthy adults, combined with a systematic review, meta-analysis and network analysis of the involvement of subcortical default mode areas in Alzheimer's disease. We conducted a systematic review and meta-analysis following PRISMA guidelines across PubMed, Scopus, Web of Science, and NeuroVault. For the meta-analysis of healthy DMN functional connectivity, we included resting-state fMRI studies that reported cortical and subcortical functional connectivity in adults (N = 5,165 across 55 experiments). For the meta-analysis of functional connectivity alterations in AD, we analyzed functional connectivity changes with respect to healthy controls (HC; both AD < HC and AD > HC) using studies where patients met established diagnostic criteria (N = 1353 across 40 experiments). Activation Likelihood Estimation (ALE; Laird, 2005) was used to identify consistent DMN regions and altered connectivity sites. Functional connectivity maps were empirically validated using the 7T resting-state data from the Human Connectome Project Young Adults (HCP-YA) dataset (N = 172). Conjunction analyses highlighted overlapping connectivity disruptions between the DMN and AD pathology.
Results:
Our results show that, besides the well-known cortical default mode network brain regions, the default mode network consistently includes subcortical regions, namely the thalamus, lobule and vermis IX and right Crus I/II of the cerebellum and the amygdala. Network analysis also suggests the involvement of the caudate nucleus. In Alzheimer's disease, we observed a left-lateralized cluster of decrease in functional connectivity which covered the medial temporal lobe and amygdala and which showed overlap with the default mode network in a portion covering parts of the left anterior hippocampus and left amygdala. This cluster also showed functional connectivity to the default mode network. We also found an area of increase in functional connectivity in the right anterior insula, which mostly connected to salience attention regions.
Conclusions:
Our published findings emphasize the consistent inclusion of subcortical regions in the DMN (namely the thalamus, amygdala, and specific cerebellar areas, with potential further involvements of the caudate nucleus and brainstem) and their susceptibility to AD pathology, particularly in the left hippocampus and amygdala (Seoane, 2024). This aligns with evidence of the susceptibility of the medial temporal lobe to Alzheimer's pathology, particularly tau accumulation, and highlights the potential role of the amygdala as an alternative route for early tangle propagation.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 2
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural)
Task-Independent and Resting-State Analysis
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Subcortical Structures 1
Novel Imaging Acquisition Methods:
BOLD fMRI
Keywords:
Sub-Cortical
Other - default mode network; Alzheimer's disease; functional connectivity
1|2Indicates the priority used for review
Abstract Information
By submitting your proposal, you grant permission for the Organization for Human Brain Mapping (OHBM) to distribute your work in any format, including video, audio print and electronic text through OHBM OnDemand, social media channels, the OHBM website, or other electronic publications and media.
The Open Science Special Interest Group (OSSIG) is introducing a reproducibility challenge for OHBM 2025. This new initiative aims to enhance the reproducibility of scientific results and foster collaborations between labs. Teams will consist of a “source” party and a “reproducing” party, and will be evaluated on the success of their replication, the openness of the source work, and additional deliverables. Click here for more information. Propose your OHBM abstract(s) as source work for future OHBM meetings by selecting one of the following options:
Please indicate below if your study was a "resting state" or "task-activation” study.
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Was this research conducted in the United States?
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.
Were any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.
Please indicate which methods were used in your research:
For human MRI, what field strength scanner do you use?
Which processing packages did you use for your study?
Provide references using APA citation style.
Aguilar, D. D. et al. (2022). Subcortical control of the default mode network: Role of the basal forebrain and implications for neuropsychiatric disorders. Brain Research Bulletin, 185, 129–139. https://doi.org/10.1016/j.brainresbull.2022.05.005
Alves, P. N. et al. (2019). An improved neuroanatomical model of the default-mode network reconciles previous neuroimaging and neuropathological findings. Communications Biology, 2(1), 370. https://doi.org/10.1038/s42003-019-0611-3
Choi, E. Y. et al. (2012). The organization of the human striatum estimated by intrinsic functional connectivity. Journal of Neurophysiology, 108(8), 2242–2263. https://doi.org/10.1152/jn.00270.2012
Laird, A. R. et al. (2005). ALE meta‐analysis: Controlling the false discovery rate and performing statistical contrasts. Human Brain Mapping, 25(1), 155–164. https://doi.org/10.1002/hbm.20136
Li, J. et al. (2021). Mapping the subcortical connectivity of the human default mode network. NeuroImage, 245, 118758. https://doi.org/10.1016/j.neuroimage.2021.118758
Raichle, M. E. et al. (2001). A default mode of brain function. Proceedings of the National Academy of Sciences, 98(2), 676–682. https://doi.org/10.1073/pnas.98.2.676
Seoane, S. et al. (2024). The subcortical default mode network and Alzheimer’s disease: A systematic review and meta-analysis. Brain Communications, 6(2), fcae128. https://doi.org/10.1093/braincomms/fcae128
Stouffer, K. M. et al. (2024). Amidst an amygdala renaissance in Alzheimer’s disease. Brain, 147(3), 816–829. https://doi.org/10.1093/brain/awad411
Yao, H. et al. (2013). Decreased functional connectivity of the amygdala in Alzheimer’s disease revealed by resting-state fMRI. European Journal of Radiology, 82(9), 1531–1538. https://doi.org/10.1016/j.ejrad.2013.03.019