Distinct Resting-State Functional Brain Connectivity Profiles in Healthy Aging and Parkinson’s Disease-Driven Neurodegeneration Open Access

Bajaj, Neha (Spring 2025)

Permanent URL: https://etd.library.emory.edu/concern/etds/6395w874z?locale=en++PublishedPublished
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Abstract

Background: Parkinson’s disease (PD) is the second most prevalent age-associated progressive neurodegenerative disorder. Clinically, PD is characterized by four cardinal motor signs: rigidity, tremors, bradykinesia, and postural instability. These signs define the progression and major characteristics of PD that contribute to significant motor and cognitive challenges of people with PD (PwPD). Previous studies have sought to identify the brain patterns that might underlie these impairments in PwPD versus the healthy older adult (HOA) population. In this study, we used resting-state functional Magnetic Resonance Imaging (fMRI) to compare functional connectivity patterns between PwPD and HOA and focused our analyses on brain regions previously shown to be involved in brain pathways supporting internally generated, externally generated movements, or both. Our hypothesis was that PwPD would be more affected in brain regions supporting IG movements. This study aims to shed light on the functional connectivity underlying PD using a well-powered and controlled design intended to inform PD neurobiology. 

Methods: 72 PwPD and 24 neurotypical age-matched HOA underwent a 9 minute and 45 second resting-state fMRI scan via a research-dedicated 3T Siemens Trio scanner using a Siemens 12-channel head coil. Brain regions of interest were selected based on independently identified, (NeuroMark) highly reproducible components. 

Results: We identified multiple pairwise combinations between brain regions that were either significantly (p<0.05) overconnected or under connected in PwPD, when compared to HOA. Brain areas that emerged in several significant findings were the cerebellum, postcentral gyrus, and the precuneus. Specifically, we found a preferential increase in the connectivity of these three brain areas in IG movement pathways in PwPD vs. HOA.

Discussion: Our findings agree with changes in connectivity in PwPD in the cerebellum, postcentral gyrus, and the precuneus. This could be attributed to PwPD overcompensating connectivity in these areas to support brain regions such as the basal ganglia in generating movements. Based on previous literature, the brain regions where more changes were identified in PwPD correspond to areas involved largely in IG pathways. In HOA, these areas are involved in both EG and IG, indicating different pathways supporting these movements. 

Conclusions: The cerebellum, postcentral gyrus, and precuneus have all been shown to increase in functional connectivity in internally generated movement pathways in PwPD vs. HOA. These findings can inform future intervention based treatment plans for PwPD.

Table of Contents

Background & Introduction - 1

Methods - 3

Participant Screening - 3  

Resting-State Functional Magnetic Resonance Imaging Procedure - 4

Resting-State Functional Magnetic Resonance Imaging Data Preprocessing - 5

Regions of Interest selected within Internally Generated & Externally Generated Pathways - 5

Independent Component Analysis -13

Statistical Analyses -16

Results - 16

Discussion - 23

Anthropological Implications - 26

Limitations -27

Conclusion - 28

References - 29

Table 1. Participant Demographics and Clinical Characteristics - 4

Table 2. Literature Review of Internally and Externally Generated Movements - 6

Table 3. Peak MNI Coordinates of Selected NeuroMark Independent Components - 14

Table 4. P-values of Significant Pairwise Comparisons between 27 selected NeuroMark Independent Components - 20

Figure 1. Statistically Significant Functional Connectivity Heat Map between 27 selected NeuroMark ICs - 18

Figure 2. Statistically Significant Functional Connections between 27 Selected NeuroMark ICs in PwPD vs. HOA - 19

Supplementary Table 1. Literature Review 

Supplementary Figure 1. Significant and Non-Significant Pairwise Comparisons between 27 Selected Neuromark Independent Components

Supplementary Figure 2. Significant and Non-Significant t-statistics of Pairwise Comparisons between 27 Selected Neuromark Independent Components

Supplementary Figure 3-30. Spatial Maps of all 27 selected NeuroMark Independent Components

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Distinct Resting-State Functional Brain Connectivity Profiles in Healthy Aging and Parkinson’s Disease-Driven Neurodegeneration () 2025-04-08 22:06:04 -0400

Supplemental Files

Thumbnail Title Date Uploaded Actions
Supplementary Table 1: Literature Review (Literature Review) 2025-04-08 22:06:10 -0400
Supplementary Figure 1: Significant and Non-Significant Pairwise Comparisons between 27 Selected NeuroMark Independent Components (Significant and Non-Significant Pairwise Comparisons between 27 Selected NeuroMark Independent Components) 2025-04-08 22:06:20 -0400
Supplementary Figure 2: Significant and Non-Significant t-statistics of Pairwise Comparisons between 27 Selected NeuroMark Independent Components (Significant and Non-Significant t-statistics of Pairwise Comparisons between 27 Selected NeuroMark Independent Components) 2025-04-08 22:06:37 -0400
Supplementary Figures 3-30: Spatial Maps of all 27 selected NeuroMark Independent Components (Spatial Maps of all 27 selected NeuroMark Independent Components. ) 2025-04-08 22:06:51 -0400