Objective: 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.

Background: While anxiety is among the most frequent non-motor manifestations in PD, the underlying mechanisms remain largely unknown.

Method: Studies assessing anxiety symptoms in PD patients and using magnetic resonance imaging (MRI), positron emission tomography (PET) or single-photon emission tomography (SPECT) were included. The main outcome parameters were the gray-matter volume (GMV), the blood-oxygen-level-dependent (BOLD) signal and receptor binding-rates (BR).

Results: The severity of anxiety was associated with changes in the fear circuit as well as changes in the cortico-striato-thalamo-cortical limbic circuit. In the fear circuit, a reduced GMV of the amygdala and the anterior cingulate cortex (ACC) was reported as well as increased functional connectivity between the amygdala and orbitofrontal cortex (OFC) and the hippocampus, between the striatum and the medial prefrontal cortex, temporal cortex and insula, and a reduced functional connectivity between the lateral prefrontal cortex and the OFC, hippocampus and amygdala. In the cortico-striato-thalamo-cortical limbic circuit, a reduced functional connectivity was reported between the striatum and ACC, a reduced dopaminergic and noradrenergic BR in striatum, thalamus and locus coeruleus, and a reduced serotoninergic BR in thalamus.

Conclusion: Anxiety is associated with structural and functional changes in both the hypothesized fear circuit as well as the limbic cortico-striato-thalamocortical circuit. 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. Further studies focusing on the structural and functional connectivity of these structures are needed in order to develop a more comprehensive hypothesis of the underlying biological mechanisms of anxiety in PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/neuroimaging-of-anxiety-in-parkinsons-disease-a-systematic-review/