Aberrant Intrinsic Activity and Connectivity in Cognitively Normal Parkinson’s Disease

Abstract

Disturbances in intrinsic activity during resting-state functional MRI (rsfMRI) are common in Parkinson’s disease (PD), but have largely been studied in a priori defined subnetworks. The cognitive significance of abnormal intrinsic activity is also poorly understood, as are abnormalities that precede the onset of mild cognitive impairment. To address these limitations, we leveraged three different analytic approaches to identify disturbances in rsfMRI metrics in 31 cognitively normal PD patients (PD-CN) and 30 healthy adults. Subjects were screened for mild cognitive impairment using the Movement Disorders Society Task Force Level II criteria. Whole-brain data-driven analytic approaches first analyzed the amplitude of low-frequency intrinsic fluctuations (ALFF) and regional homogeneity (ReHo), a measure of local connectivity amongst functionally similar regions. We then examined if regional disturbances in these metrics altered functional connectivity with other brain regions. We also investigated if abnormal rsfMRI metrics in PD-CN were related to brain atrophy and executive, visual organization, and episodic memory functioning. The results revealed abnormally increased and decreased ALFF and ReHo in PD-CN patients within the default mode network (posterior cingulate, inferior parietal cortex, parahippocampus, entorhinal cortex), sensorimotor cortex (primary motor, pre/post-central gyrus), basal ganglia (putamen, caudate), and posterior cerebellar lobule VII, which mediates cognition. For default mode network regions, we also observed a compound profile of altered ALFF and ReHo. Most regional disturbances in ALFF and ReHo were associated with strengthened long-range interactions in PD-CN, notably with regions in different networks. Stronger long-range functional connectivity in PD-CN was also partly expanded to connections that were outside the networks of the control group. Abnormally increased activity and functional connectivity appeared to have a pathological, rather than compensatory influence on cognitive abilities tested in this study. Receiver operating curve analyses demonstrated excellent sensitivity (≥90%) of rsfMRI variables in distinguishing patients from controls, but poor accuracy for brain volume and cognitive variables. Altogether these results provide new insights into the topology, cognitive relevance, and sensitivity of aberrant intrinsic activity and connectivity that precedes clinically significant cognitive impairment. Longitudinal studies are needed to determine if these neurocognitive associations presage the development of future mild cognitive impairment or dementia.

The Relationship between Side of Onset and Cerebral Regional Homogeneity in Parkinson’s Disease: A Resting-State fMRI Study

“…In the present study, both LPD and RPD patients displayed increased ReHo in the right temporal pole. Previous studies have also identified this area with abnormal ReHo in PD, but its clinical significance in PD has rarely been discussed [ 34 – 37 ]. Although the two groups had different patterns of asymmetry of motor symptoms, most of the patients had bilateral motor symptoms.…”

A Radiomics Approach to Predicting Parkinson’s Disease by Incorporating Whole-Brain Functional Activity and Gray Matter Structure

“…A meta-analysis using ALFF and ReHo found consistent decreased activity in the putamen for PD patients that could serve as an independent validation of rs-fMRI (Wang et al, 2018). Another ALFF and ReHo based study demonstrated the disturbed DMN, SMA, basal ganglia (BG), and posterior cerebellar lobule in cognitively normal PD as compared with healthy controls (Harrington et al, 2017). These multilevel characteristics of rs-fMRI could effectively improve the discrimination accuracy of diagnosis.…”

The Functional and Structural Changes of the Brain in Parkinson's Disease Patients with Mild Cognitive Impairment

“…Many studies have found extensive disturbances of ALFF in PD [10,11]. To be illustrated, Compared with the cognitively normal PD patients (PD-NCI), PD patients with mild cognitive impairment (PD-MCI) exhibited increased ALFF in the right inferior parietal cortex and left posterior cerebellum and decreased ALFF in the posterior cingulate and bilateral putamen [12]. In addition, both decreased ALFF values have been observed in the right superior temporal gyrus and increased ALFF values have been also found in the left superior frontal gyrus in the PD-MCI patient group compared to healthy control (HC) group [13].…”