Amygdala hypoconnectivity is mediated by the NBM in Parkinson’s patients with visual hallucinations
Poster No:
223
Submission Type:
Abstract Submission
Authors:
Anna Ignatavicius1, Lachlan Churchill1, Ajay Konuri1, Jack Anderson1, Simon Lewis2, Elie Matar1
Institutions:
1University of Sydney, Sydney, NSW, 2Macquarie University, Sydney, NSW
First Author:
Co-Author(s):
Introduction:
Visual hallucinations (VH) are a common and troubling non-motor feature of Parkinson's disease (PD), associated with a more aggressive clinical trajectory (Aarsland et al., 2000; Gryc et al., 2020). The pathophysiological mechanisms of VH are thought to be driven by impaired coordination of large-scale brain networks, localised distribution of pathology and dysfunctional modulation from ascending neurotransmitter systems (Collerton et al., 2023). Both elevated pathological burden in the amygdala and cholinergic deficits within visual attentional networks have been consistently linked to VH in PD (Harding et al., 2002; Ignatavicius et al., 2024). With widespread projections to most of the cortex, the amygdala and the nucleus basalis of Meynert (NBM) cholinergic system are uniquely positioned to integrate sensory and attentional information (Ignatavicius et al., 2024; Pessoa & Adolphs, 2010). However, few studies have explored whether disrupted functional connectivity between these subcortical regions and with cortical networks that support perceptual processing may contribute to VH. In this study, we sought to investigate whether altered amygdala and NBM resting-state functional connectivity (FC) is associated with the presence of VH in PD.
Methods:
Seventy PD patients (30 with VH and 40 without VH) underwent resting-state fMRI (GE systems) and clinical assessments while on their usual dopaminergic medications. Mean time-series were extracted from resting-state fMRI data using a composite atlas that combined 400 cortical regions using the Schaefer parcellation (Schaefer et al., 2018), 54 subcortical regions from the Tian parcellation (Tian et al., 2020), and a probabilistic anatomical map of the NBM (Zaborszky et al., 2008). Connectivity matrices were computed for each subject by calculating Pearson correlation coefficients between the time-series of all regions, followed by Fisher z-transformation. Seed-based FC analyses were performed to examine group differences in FC between the bilateral amygdala and NBM and resting-state networks (Yeo et al., 2011) previously associated with VH (Collerton et al., 2023). These included the visual network (VIS), dorsal attentional network (DAN), ventral attentional network (VAN), default mode network (DMN), and frontoparietal network (FPN). Group differences in FC were evaluated using non-parametric permutation testing (10,000 permutations) with FDR correction applied for multiple comparisons (q < 0.05). Mediation analyses combining linear and logistic regression models were conducted to determine whether NBM FC influenced the relationship between amygdala FC and VH. All statistical analyses included age and sex as covariates.
Results:
PD-VH patients exhibited reduced FC between the amygdala bilaterally and the VIS and between the left amygdala and both the DAN and VAN compared to PD-No VH (p < 0.05; FDR, Fig. 1). A trend toward reduced left NBM-VAN FC was observed in PD-VH but did not survive correction (p = 0.02, uncorrected). No group differences were found in NBM-amygdala FC. Mediation analysis (Fig. 2) revealed that NBM-VAN FC significantly mediated the relationship between amygdala-VAN FC and VH (indirect effect: -0.48, 95% CI = [-1.02, -0.10], direct effect: p = 0.07). Partial mediation was also found for the relationship between amygdala-DAN FC and VH (indirect effect: -0.37, 95% CI = [-0.87, -0.04], direct effect: p = 0.01).
Conclusions:
Hypoconnectivity between the amygdala and key functional networks known to support visual and attentional processing is linked to VH in PD, underscoring the critical role of this region to the mechanisms that drive abnormal perceptual experiences. The relationship between amygdala-attentional network FC and VH is at least partially mediated by the integrity of the interactions between the NBM and the VAN. Therefore, targeting the cholinergic system may help restore network function and provide therapeutic benefit for this distressing symptom.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural) 2
Perception, Attention and Motor Behavior:
Attention: Visual
Perception: Visual
Keywords:
Acetylcholine
Degenerative Disease
FUNCTIONAL MRI
Limbic Systems
Neurological
Perception
Sub-Cortical
Other - Hallucinations
1|2Indicates the priority used for review
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Provide references using APA citation style.
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