Mild Thyrotoxicosis Leads to Brain Perfusion Changes: An Arterial Spin Labelling Study

Abstract

Hypo- and hyperthyroidism have effects on brain structure and function, as well as cognitive processes, including memory. However, little is known about the influence of thyroid hormones on brain perfusion and the relationship of such perfusion changes with cognition. The present study aimed to demonstrate the effect of short-term experimental hyperthyroidism on brain perfusion in healthy volunteers and to assess whether perfusion changes, if present, are related to cognitive performance. It is known that an interaction exists between brain perfusion and cerebral oxygen consumption rate and it is considered that neural activation increases cerebral regional perfusion rate in brain areas associated with memory. Measuring cerebral blood flow may therefore represent a proxy for neural activity. Therefore, arterial spin labelling (ASL) measurements were conducted and later analysed to evaluate brain perfusion in 29 healthy men before and after ingesting thyroid hormones for 8 weeks. Psychological tests concerning memory were performed at the same time-points and the results were correlated with the imaging results. In the hyperthyroid condition, perfusion was increased in the posterior cerebellum in regions connected with cerebral networks associated with cognitive control and the visual cortex compared to the euthyroid condition. In addition, these perfusion changes were positively correlated with changes of performance in the German version of the Auditory Verbal Learning Task [AVLT, Verbaler Lern-und-Merkfähigkeits-Test (VLMT)]. Cerebellar perfusion and function therefore appears to be modulated by thyroid hormones, likely because the cerebellum hosts a high number of thyroid hormone receptors.

Partial withdrawal of levothyroxine treated disease leads to brain activations and effects on performance in a working memory task: A pilot study

“…The high expression of TRalpha characterised during cerebellar development is in line with our present finding of a particularly high vulnerability of cerebellar structures to small changes in thyroid function even in adults. This hypothesis also fits with our previous work in experimental hyperthyroidism where, amongst other regions, cerebellar activation is altered in a comparable memory task (Figure and Table ).…”

“…Previously, our group used structural and functional MRI, with the latter in conjunction with an n‐back task, to assess a model of experimentally induced hyperthyroidism . The fMRI study revealed an effect of task difficulty in the parahippocampal gyrus, supplementary motor area, prefrontal cortex, anterior cingulate cortex, posterior cerebellum, rolandic operculum and insula, with a modulation of this effect by thyroid status (hyperthyroid vs euthyroid) in the right prefrontal cortex and the right parahippocampal area.…”

Structural brain changes in hyperthyroid Graves’ disease: protocol for an ongoing longitudinal, case-controlled study in Göteborg, Sweden—the CogThy project

“…Previous attempts to visualise and understand thyroid–brain interaction combined neuroimaging with neurophysiological and neuropsychiatric investigations 22 90. Cognition is complex and, as such, involves widely distributed functional systems and several brain regions, among which the MTL and the prefrontal cortex are generally recognised as being of central importance.…”

“…The posterior cerebellum, among other regions, is probably relevant for cognition in GD. Experimentally induced hyperthyroidism increases brain perfusion in posterior cerebellar regions connected with cerebral networks thought to be associated with cognitive control 90. In the German version of the Auditory Verbal Learning scale, these perfusion changes are positively correlated with changes in performance 90.…”

Aberrant intra and inter network resting state functional connectivity in thyrotoxicosis

“…Previous neuroimaging studies have shown morphological, functional, metabolite and perfusion weighted changes associated with thyrotoxicosis. A functional magnetic resonance imaging (fMRI) study using the N‐back working memory task revealed altered activation in brain regions such as the parahippocampal gyrus, supplementary motor area, prefrontal cortex, anterior cingulate cortex, posterior cerebellum, rolandic operculum and insula in thyrotoxicosis .…”