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Psychoneuroendocrinology. 2019 Apr;102:158-163. doi: 10.1016/j.psyneuen.2018.12.012. Epub 2018 Dec 12.

Experimentally induced subclinical hypothyroidism causes decreased functional connectivity of the cuneus: A resting state fMRI study.

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Department of Neurology, University of Lübeck, Lübeck, Germany. Electronic address:
Department of Neurology, University of Lübeck, Lübeck, Germany.
Department of Neurology, University of Lübeck, Lübeck, Germany; Department of Psychology II, University of Lübeck, Lübeck, Germany.
Department of Internal Medicine I, University of Lübeck, Lübeck, Germany.
Central Institute of Mental Health, Mannheim, Germany.



The aim of this study was to experimentally evaluate the effects of subclinical mild hypothyroidism on brain network connectivity as determined by resting state fMRI (rsfMRI) which serves as a proxy for global changes in brain function.


Fifteen otherwise healthy patients with complete hypothyroidism under stable, long term levothyroxine substitution volunteered for the study. They reduced their pretest levothyroxine dosage by 30% for 52-56 days. Basally and after partial levothyroxine withdrawal, rsfMRI along with a neuropsychological analysis was performed. RsfMRI was subjected to graph-theory-based analysis to investigate whole-brain intrinsic functional connectivity.


The desired subclinical hypothyroidism was achieved in all subjects. This was associated with a significant decrease in resting-state functional connectivity specifically in the cuneus (0.05 FWE corrected at cluster level) which was mainly caused by a weaker functional connectivity to the cerebellum and regions of the default mode network, i.e. the medial prefrontal cortex, the precuneus and the bilateral angular gyri. The decrease in cuneus connectivity was correlated to the increase in TSH serum levels. A working memory task showed a slightly longer reaction time and less accuracy after partial levothyroxine withdrawal.


Even short-term partial levothyroxine partial withdrawal leads to deficits in working memory tasks and to a weaker integration of the cuneus within the default mode network.


Hypothyroidism; Memory; Resting state; Thyroid; rsfMRI

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