Altered brain functional connectivity in patients with resistance to thyroid hormone ß

To investigate changes in brain network organization and possible neurobehavioral similarities to attention-deficit hyperactivity disorder (ADHD), we measured changes in brain resting-state functional connectivity (rs-fMRI) and cognitive domains in patients with resistance to thyroid hormone β (RTHβ) and compared them with those in healthy control subjects. In this prospective case-control study, twenty-one participants with genetically confirmed RTHβ were matched with 21 healthy controls. The Adult ADHD Self-Report Scale (ASRSv1.1) and ADHD Rating Scale-IV were used to assess self-reported symptoms of ADHD. A voxel-wise and atlas-based approach was used to identify changes in the brain networks. The RTHβ group reported behavioral symptoms similar to those of ADHD. We found evidence of weaker network integration of the lingual and fusiform gyri in the RTHβ group, which was mainly driven by weaker connectivity to the bilateral insula and supplementary motor cortex. Functional connectivity between regions of the default mode network (angular gyrus/middle temporal gyrus) and regions of the cognitive control network (bilateral middle frontal gyrus) was increased in RTHβ patients compared to healthy controls. Increased connectivity between regions of the default mode network and the dorsolateral prefrontal cortex is frequently reported in ADHD and is interpreted to be associated with deficits in attention. Our finding of weaker connectivity of the lingual gyrus to the bilateral insula (salience network) in RTHβ patients has also been reported previously in ADHD and may reflect decreased habituation to visual stimuli and increased distractibility. Overall, our observations support the notion of neuropsychological similarities between RTHβ and ADHD.