Neuroimaging of Anxiety in Parkinson's Disease: A Systematic Review

Abstract

Background: The aim of this systematic review was (1) to identify the brain regions involved in anxiety in Parkinson's disease (PD) based on neuroimaging studies and (2) to interpret the findings against the background of dysfunction of the fear circuit and limbic cortico-striato-thalamocortical circuit.

Methods: Studies assessing anxiety symptoms in PD patients and studies using magnetic resonance imaging, positron emission tomography, or single-photon emission computed tomography were included.

Results: The severity of anxiety was associated with changes in the fear circuit and the cortico-striato-thalamocortical limbic circuit. In the fear circuit, a reduced gray-matter volume of the amygdala and the anterior cingulate cortex (ACC); an increased functional connectivity (FC) between the amygdala and orbitofrontal cortex (OFC) and hippocampus and between the striatum and the medial prefrontal cortex (PFC), temporal cortex, and insula; and a reduced FC between the lateral PFC and the OFC, hippocampus, and amygdala were reported. In the cortico-striato-thalamocortical limbic circuit, a reduced FC between the striatum and ACC; a reduced dopaminergic and noradrenergic activity in striatum, thalamus, and locus coeruleus; and a reduced serotoninergic activity in the thalamus were reported.

Conclusion: To conclude, anxiety is associated with structural and functional changes in both the hypothesized fear and the limbic cortico-striato-thalamocortical circuits. These circuits overlap and may well constitute parts of a more extensive pathway, of which different parts play different roles in anxiety. The neuropathology of PD may affect these circuits in different ways, explaining the high prevalence of anxiety in PD and also the associated cognitive, motor, and psychiatric symptoms. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: Parkinson's disease; anxiety; fear circuit; imaging; limbic circuit.

FIG. 1

Schematic representation of the fear circuit and cortico‐striato‐thalamocortical limbic circuit in human brain: (a) interactions model in normal brain as reported in the literature; ⁶ , ⁸ , ³⁹ (b) fear and limbic circuit changes in Parkinson's disease anxiety found in this systematic review. The blue area corresponds to the structures with a reduced receptor binding for dopamine and noradrenaline, but no information on structural and functional connectivity changes for the basal ganglia and thalamus has been reported in these studies. Therefore, it does not mean that there is no change. Abbreviations: ACC, anterior cingulate cortex; BLA, basolateral nucleus of amygdala; BNST, bed nucleus of the stria terminalis; CeA, centromedial nucleus of amygdala; GP(e/i), globus pallidus (external/internal); HypoTh, hypothalamus; OFC, orbitofrontal cortex; (m/dl/vl)PFC, (medial/dorsolateral/ventrolateral) prefrontal cortex; STN, subthalamic nucleus. [Color figure can be viewed at wileyonlinelibrary.com]