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Peer-reviewedCC BYNeuroImage. Clinical

Thalamocortical connectivity associated with fatigue after accounting for depressive symptoms in stroke survivors and controls.

  • Joan Stilling1
  • Christie Gillies2
  • Ji Hyun Kim3
  • Keith Jamison4
  • Amy Kuceyeski5
5 affiliations
  1. 1Weill Cornell Medicine, Department of Rehabilitation Medicine, New York, NY, United States of America. Electronic address: [email protected].
  2. 2Weill Cornell Medicine, Department of Neuroscience, New York, NY, United States of America.
  3. 3New York Medical College, Valhalla, NY, United States of America.
  4. 4Weill Cornell Medicine, Department of Radiology, New York, NY, United States of America.
  5. 5Weill Cornell Medicine, Department of Radiology, New York, NY, United States of America; Cornell University, Computational Biology & Statistics and Data Science, Ithaca, NY, United States of America.
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Abstract

Background

Post-stroke fatigue is common and disabling, yet rarely distinguished from co-occurring depression, limiting understanding of its neural substrates. We examined resting-state fMRI correlates of post-stroke fatigue while accounting for depressive symptoms.Methods

We studied 103 stroke patients and 29 age-matched controls from a longitudinal neuroimaging cohort. Fatigue was assessed via the SF-36 Vitality subscale and depression via the Geriatric Depression Scale - Short (GDS-15). Linear mixed-effects models evaluated associations between vitality and resting-state functional connectivity, adjusting for depression and covariates. Residualized vitality models served as sensitivity analyses to isolate fatigue variance independent of depressive symptoms, with FDR correction applied within feature families.Results

In depression-adjusted models, higher vitality (lower fatigue) was associated with increased frontoparietal-limbic connectivity (β = 0.0013, FDR q = 0.048), though this did not survive depression residualization. In a residualized sensitivity analysis, higher vitality (lower fatigue) was associated with reduced thalamus-insula and thalamus-ventral attention network connectivity (thalamus-insula: β = -0.0071, FDR q = 0.011; thalamus-VAN: β = -0.0043, FDR q = 0.012); these associations were attenuated and did not survive correction in the primary depression-adjusted model (q ≈ 0.075).Conclusions

Fatigue was associated with both frontoparietal-limbic and thalamocortical connectivity, although the thalamic associations were attenuated after adjustment for depressive symptoms in the primary analysis and were most evident in residualized sensitivity analyses. These findings suggest that fatigue and depressive symptoms may involve both shared and potentially distinct neural correlates. Point estimates were smaller in stroke participants than controls, providing no evidence that the observed associations were stroke-specific. Future work should determine whether these relationships are unique to stroke or reflect broader neural correlates of fatigue across clinical populations.

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Cite

BibTeXRIS
BibTeX
@article{stilling2026thalamocortical,
  title = {{Thalamocortical connectivity associated with fatigue after accounting for depressive symptoms in stroke survivors and controls.}},
  author = {Joan Stilling and Christie Gillies and Ji Hyun Kim and Keith Jamison and Amy Kuceyeski},
  journal = {NeuroImage. Clinical},
  year = {2026},
  month = oct,
  doi = {10.1016/j.nicl.2026.104063},
  url = {https://europepmc.org/article/MED/42858620},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Thalamocortical connectivity associated with fatigue after accounting for depressive symptoms in stroke survivors and controls.
AU  - Joan Stilling
AU  - Christie Gillies
AU  - Ji Hyun Kim
AU  - Keith Jamison
AU  - Amy Kuceyeski
PY  - 2026
DA  - 2026/10/08
JO  - NeuroImage. Clinical
DO  - 10.1016/j.nicl.2026.104063
UR  - https://europepmc.org/article/MED/42858620
AB  - Background  Post-stroke fatigue is common and disabling, yet rarely distinguished from co-occurring depression, limiting understanding of its neural substrates. We examined resting-state fMRI correlates of post-stroke fatigue while accounting for depressive symptoms.Methods  We studied 103 stroke patients and 29 age-matched controls from a longitudinal neuroimaging cohort. Fatigue was assessed via the SF-36 Vitality subscale and depression via the Geriatric Depression Scale - Short (GDS-15). Linear mixed-effects models evaluated associations between vitality and resting-state functional connectivity, adjusting for depression and covariates. Residualized vitality models served as sensitivity analyses to isolate fatigue variance independent of depressive symptoms, with FDR correction applied within feature families.Results  In depression-adjusted models, higher vitality (lower fatigue) was associated with increased frontoparietal-limbic connectivity (β = 0.0013, FDR q = 0.048), though this did not survive depression residualization. In a residualized sensitivity analysis, higher vitality (lower fatigue) was associated with reduced thalamus-insula and thalamus-ventral attention network connectivity (thalamus-insula: β = -0.0071, FDR q = 0.011; thalamus-VAN: β = -0.0043, FDR q = 0.012); these associations were attenuated and did not survive correction in the primary depression-adjusted model (q ≈ 0.075).Conclusions  Fatigue was associated with both frontoparietal-limbic and thalamocortical connectivity, although the thalamic associations were attenuated after adjustment for depressive symptoms in the primary analysis and were most evident in residualized sensitivity analyses. These findings suggest that fatigue and depressive symptoms may involve both shared and potentially distinct neural correlates. Point estimates were smaller in stroke participants than controls, providing no evidence that the observed associations were stroke-specific. Future work should determine whether these relationships are unique to stroke or reflect broader neural correlates of fatigue across clinical populations.
SN  - 2213-1582
ER  -