Right-lateralized maladaptive topological reorganization in hyperthyroidism

Area of Science:

• Neuroscience
• Endocrinology
• Medical Imaging

Background:

• Hyperthyroidism is linked to cognitive and neuropsychiatric issues, but its impact on brain white matter and neuromolecular organization is unclear.
• Understanding these changes is crucial for developing targeted treatments for hyperthyroid-induced neurological dysfunction.

Purpose of the Study:

• To investigate how hyperthyroidism affects white matter architecture and neuromodulatory systems.
• To explore the relationship between altered brain connectivity, thyroid hormone levels, and neurotransmitter receptor distribution.

Main Methods:

• Diffusion MRI-based structural connectomes were analyzed in 30 hyperthyroid patients and 28 healthy controls.
• Graph theoretical analysis quantified network topology; PET imaging assessed neurotransmitter receptor density.
• Statistical analyses examined associations with clinical measures, cognitive scores, and thyroid hormone levels.

Main Results:

• Hyperthyroid patients showed increased medium- and long-range connectivity, reduced modularity, and increased path length, indicating disrupted network segregation and efficiency.
• Nodal alterations were predominantly right-lateralized. Free thyroxine levels correlated with path length and long-range connectivity.
• Neurotransmitter receptor distributions, particularly for 5-HT1A and dopamine transporters, explained significant network topology variance.

Conclusions:

• Excess thyroid hormone induces right-lateralized connectomic reorganization and increased metabolic demand, mediated by serotonergic and dopaminergic systems.
• Findings link endocrine dysfunction to large-scale brain network vulnerability, suggesting potential biomarkers for clinical translation.