Disconnections in White Matter Tracts Associated with Post-Stroke Depression
Presented During: Poster Session 3
Friday, June 27, 2025: 01:45 PM - 03:45 PM
Friday, June 27, 2025: 01:45 PM - 03:45 PM
Presented During: Poster Session 4
Saturday, June 28, 2025: 01:45 PM - 03:45 PM
Saturday, June 28, 2025: 01:45 PM - 03:45 PM
Poster No:
1778
Submission Type:
Abstract Submission
Authors:
Matthew Thurston1, Jason Mattingley1, Stephanie Forkel2, Margaret Moore1, Perminder Sachdev3, Jessica Lo3, Lena Oestreich1
Institutions:
1The University of Queensland, Brisbane, Australia, 2Donders Institute for Brain, Cognition, and Behaviour, Nijmegen, Netherlands, 3University of New South Wales, Sydney, Australia
First Author:
Co-Author(s):
Introduction:
Post-stroke depression (PSD) is a common sequela of stroke, occurring in roughly 30% of survivors (Hackett & Pickles, 2014). It can interfere with a patient's motivation to engage in rehabilitation activities and increase their risk of disability and mortality (Robinson & Jorge, 2016). Studies using traditional voxel-based lesion-symptom mapping (VLSM), a method that quantitatively analyzes the relationship between lesion locations and symptoms, have identified inconsistent key lesion sites associated with post-stroke depression (Gozzi et al., 2014). While focal lesions directly impair local brain function, their impact on white matter tracts can lead to widespread disconnection of neural networks, potentially compromising behavioral and cognitive processes (Thiebaut de Schotten et al., 2020). Here, we investigate how these lesion-induced white matter disconnections contribute to the development of PSD.
Methods:
Data were sourced from the Sydney Stroke Study (Sachdev et al., 2014), an observational stroke study of 103 individuals admitted to hospital for either ischemic stroke or transient ischemic attack (TIA). T1-weighted MRI scans (TR = 14.3ms, TE = 5.4ms, FOV = 250×250mm2, in-plane resolution 0.977×0.977mm2) were acquired using a 1.5T Signa GE scanner. Depression was measured using the Geriatric Depression Scale (GDS; Yesavage, 1988) and the Hamilton Rating Scale for Depression (HAMD; Hamilton, 1960). Depression assessments and MRI scans were conducted approximately 3-6 months after diagnosis of ischemic stroke or TIA. Manual lesion delineation was performed in MRIcron (Rorden et al., 2007) on all T1 scans in individual subject space. Lesion masks were smoothed at 5mm full width at half maximum and binarized using a 0.5 threshold. T1 images were then co-registered to MNI152 space using Advanced Normalization Tools (ANTs; Avants et al., 2010). The resulting transformation matrix was used to warp lesions to MNI space. Lesion masks were used to generate disconnectome maps using the BCBtoolkit (Foulon et al., 2018; see Figure 1A for an example patient). To examine relationships between brain disconnections and depressive symptoms, we used AnaCOM2 within the BCBtoolkit. Participants were classified as depressed (HAMD ≥ 8; GDS ≥ 5) or not depressed. Mann-Whitney tests were used to compare depression scores between these groups in disconnection clusters where at least five individuals from the depressed group showed disconnections, with results remaining significant after Holm correction.
Results:
After excluding 25 patients whose lesions were unobservable on MRI, the final sample comprised 78 patients (52 males), with a mean age of 71.9 years (SD = 8.5; range: 50-86). Lesion lateralization included 36 right-sided, 19 left-sided, and 23 bilateral lesions. Elevated depressive symptoms were present in thirteen patients based on the GDS cutoff and eight based on the HAMD cutoff. AnaCOM2 analysis revealed that HAMD scores were associated with disconnections in two white matter tract clusters, whereas GDS scores were associated with fourteen clusters (See Figure 1B and C & Table 1 for details).
Conclusions:
Our findings reveal that PSD is associated with disconnections in specific white matter pathways, particularly the inferior fronto-occipital fasciculus, corticospinal tract, and forceps major. The broader network of disconnections associated with GDS scores relative to HAMD scores may reflect the scales' different emphases, as HAMD incorporates anxiety and somatic symptoms whereas GDS focuses more specifically on depression. These results advance our understanding of the anatomical basis of post-stroke depression beyond focal lesion locations, highlighting the importance of white matter connectivity in mood disorders after stroke. Our findings could inform more targeted therapeutic approaches and help identify patients at risk of developing PSD.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 2
Modeling and Analysis Methods:
Diffusion MRI Modeling and Analysis
Image Registration and Computational Anatomy
Other Methods
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
White Matter Anatomy, Fiber Pathways and Connectivity 1
Keywords:
ADULTS
Computational Neuroscience
MRI
Neurological
Psychiatric
STRUCTURAL MRI
White Matter
Other - Stroke
1|2Indicates the priority used for review
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