Dynamic properties in functional connectivity changes and striatal dopamine deficiency in Parkinson's disease

• Published in: Human brain mapping 2024-07, Vol.45 (10), p.e26776-n/a
• Main Authors: Asendorf, Adrian L., Theis, Hendrik, Tittgemeyer, Marc, Timmermann, Lars, Fink, Gereon R., Drzezga, Alexander, Eggers, Carsten, Ruppert‐Junck, Marina C., Pedrosa, David J., Hoenig, Merle C., Eimeren, Thilo
• Format: Article
• Language: English
• Subjects: Aged; Cohort Studies; Connectome; Corpus Striatum - diagnostic imaging; Corpus Striatum - metabolism; Corpus Striatum - physiopathology; DAT SPECT; Dihydroxyphenylalanine - analogs & derivatives; Dopamine - metabolism; Dopamine Plasma Membrane Transport Proteins - metabolism; dynamic functional connectivity; Female; F‐DOPA PET; Humans; imaging; Magnetic Resonance Imaging; Male; Middle Aged; Nerve Net - diagnostic imaging; Nerve Net - metabolism; Nerve Net - physiopathology; network; Parkinson Disease - diagnostic imaging; Parkinson Disease - metabolism; Parkinson Disease - physiopathology; Positron-Emission Tomography; resting‐state fMRI; Tomography, Emission-Computed, Single-Photon
• ISSN: 1065-9471; 1097-0193; 1097-0193
• DOI: 10.1002/hbm.26776

Recent studies in Parkinson's disease (PD) patients reported disruptions in dynamic functional connectivity (dFC, i.e., a characterization of spontaneous fluctuations in functional connectivity over time). Here, we assessed whether the integrity of striatal dopamine terminals directly modulates dFC metrics in two separate PD cohorts, indexing dopamine‐related changes in large‐scale brain network dynamics and its implications in clinical features. We pooled data from two disease‐control cohorts reflecting early PD. From the Parkinson's Progression Marker Initiative (PPMI) cohort, resting‐state functional magnetic resonance imaging (rsfMRI) and dopamine transporter (DaT) single‐photon emission computed tomography (SPECT) were available for 63 PD patients and 16 age‐ and sex‐matched healthy controls. From the clinical research group 219 (KFO) cohort, rsfMRI imaging was available for 52 PD patients and 17 age‐ and sex‐matched healthy controls. A subset of 41 PD patients and 13 healthy control subjects additionally underwent 18F‐DOPA‐positron emission tomography (PET) imaging. The striatal synthesis capacity of 18F‐DOPA PET and dopamine terminal quantity of DaT SPECT images were extracted for the putamen and the caudate. After rsfMRI pre‐processing, an independent component analysis was performed on both cohorts simultaneously. Based on the derived components, an individual sliding window approach (44 s window) and a subsequent k‐means clustering were conducted separately for each cohort to derive dFC states (reemerging intra‐ and interindividual connectivity patterns). From these states, we derived temporal metrics, such as average dwell time per state, state attendance, and number of transitions and compared them between groups and cohorts. Further, we correlated these with the respective measures for local dopaminergic impairment and clinical severity. The cohorts did not differ regarding age and sex. Between cohorts, PD groups differed regarding disease duration, education, cognitive scores and L‐dopa equivalent daily dose. In both cohorts, the dFC analysis resulted in three distinct states, varying in connectivity patterns and strength. In the PPMI cohort, PD patients showed a lower state attendance for the globally integrated (GI) state and a lower number of transitions than controls. Significantly, worse motor scores (Unified Parkinson's Disease Rating Scale Part III) and dopaminergic impairment in the putamen and the caudate were associated with low ave