Abnormal functional connectivity of the amygdala is associated with depression in Parkinson's disease

Abstract

Depressive symptoms are common in Parkinson's disease (PD), but the pathophysiology and neural basis underlying depression in PD is not well understood. Abnormal functional connectivity of the amygdala with various cortical and subcortical areas has been observed in major depressive disorder, indicating that dysfunction of the corticolimbic network may be involved in the pathogenesis of major depressive disorder. However, little is known about alterations of amygdala functional connectivity in depressed PD patients. In the present study, 20 depressed PD patients, 40 nondepressed PD patients, and 43 matched healthy controls underwent neuropsychological tests and resting-state functional MRI scanning. Between-group differences in amygdala functional connectivity network were examined using t tests. Compared to the nondepressed PD patients, depressed PD patients showed increased left amygdala functional connectivity with the bilateral mediodorsal thalamus, right amygdala functional connectivity with the left superior temporal gyrus, and left calcarine gyrus. Compared to the healthy controls, the depressed PD group also showed increased left amygdala functional connectivity with the bilateral mediodorsal thalamus, but decreased left amygdala functional connectivity with the left putamen, left inferior frontal gyrus, and the right cerebellum, as well as decreased right amygdala functional connectivity with the left inferior orbitofrontal gyrus, the left gyrus rectus, and the right putamen. The increased connectivity between limbic regions and decreased connectivity between the corticolimbic networks may reflect impaired high-order cortical regulatory effects on the emotion-related limbic areas, which may lead to mood dysregulation. Our study should advance the understanding of neural mechanisms underlying depression in PD.

Altered directional connectivity between emotion network and motor network in Parkinson's disease with depression

“…[8,10,11] Furthermore, the current study has extended the previous studies by identifying the aberrant interactions among MN, EN, DMN, and DAN in DPD. These results provide new evidence for the notation that DPD can be characterized as a functional disconnection syndrome.…”

“…All these previous studies focus on regional deficits [8] and/or functional connectivity abnormalities of a specific network. [9–11] These results revealed impairments of many brain regions in the motor network, default mode network, and emotion network as well as many functional pathways among these networks in DPD patients, as compared with non-depressed PD (NDPD) and normal controls (NC).…”

“…However, previous studies mainly focused on the comparison of DPD and NDPD, [8–11] without explicitly comparing DPD and MDD. Given that DPD is the comorbidity of PD and depression, any potentially specific biomarker should differentiate DPD from both NDPD and MDD.…”

Depression, anxiety, and apathy in Parkinson's disease: insights from neuroimaging studies

“…Of the 38 studies on depression, 33 reported findings from one single imaging modality: 19 used either PET [11, 12, 13,15, 16, 17, 18, 19] or SPECT 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 techniques, four used T1‐weighted imaging 31, 32, 33, three used DTI 34, 35, 36, six used resting state functional MRI (RS‐FMRI) 37, 38, 39, 40, 41, 42 and two used TCS methods 43, 44. The remaining four of the 38 studies reported findings from structural T1‐weighted imaging plus another imaging method, including PET 14, DTI 45, task FMRI 46 and RS‐FMRI 47, respectively.…”

Neuropsychiatric symptoms in untreated Parkinson’s disease

“…Bilateral decreases in regional cerebral blood flow of the medial prefrontal cortex is also a common finding in PD patients with depression 56. Abnormal functional connectivity of the amygdala, the prefrontal-limbic system, the prefrontal cortex, and the lingual gyrus was associated with depressive symptoms in PD patients;57,58 however, a study found intact limbic-prefrontal connections54 in a similar group of patients. Furthermore, depression in PD is also related to gray and white matter volume deterioration in the orbitofrontal and temporal regions as well as in the cortical-limbic system 59–61.…”