Anxiety in Parkinson's disease is associated with reduced structural covariance of the striatum

Background: Anxiety is highly prevalent in Parkinson's disease (PD) and has great negative impact on quality of life. Functional and structural neuroimaging studies have contributed to our understanding of the symptomatology of PD but still little is known about the pathophysiology of PD-related anxiety. Methods: We used seed-based structural covariance analysis to study the anatomical network correlates of anxiety in PD. Structural covariance analysis is based on the statistical correlation between regional brain volumes measured on T1-weighted magnetic resonance images. We investigated the association between anxiety symptoms, as measured by the Beck Anxiety Inventory (BAI), and seed-to-whole-brain structural covariance networks in 115 patients with idiopathic PD using five bilateral seeds: basolateral amygdala, centromedial-superficial amygdala, dorsal caudate nucleus, dorsal-caudal putamen, and nucleus accumbens. Results: Severity of anxiety correlated negatively with structural covariance between the left striatal sub-regions and the contralateral caudate nucleus. Moreover, severity of anxiety was associated with reduced structural covariance between the right dorsal caudate nucleus and ipsilateral ventrolateral prefrontal cortex and between the left nucleus accumbens and ipsilateral dorsolateral prefrontal cortex. Structural covariance of the amygdalar seeds did not correlate with anxiety. Conclusions: We interpret these findings as a reduced interhemispheric cooperation between the left and right striatum and reduced prefrontal-striatal connectivity, possibly related to impaired 'top-down' regulation of emotions. These findings shed more light on the pathophysiology of PD-related anxiety Limitations: This study did not include PD patients with an anxiety disorder.