Abstract
Alterations in time-varying functional connectivity (FC) have been found in Parkinson’s disease (PD) patients. To date, very little is known about the influence of sex on brain FC in PD patients and how this could be related to disease severity. The first objective was to evaluate the influence of sex on dynamic FC characteristics in PD patients and healthy controls (HC), while the second aim was to investigate the temporal patterns of dynamic connectivity related to PD motor and non-motor symptoms. Ninety-nine PD patients and sixty-two HC underwent a neuropsychological and clinical assessment. Rs-fMRI and T1-weighted MRI were also acquired. Dynamic FC analyses were performed in the GIFT toolbox. Dynamic FC analyses identified two States: State I, characterized by within-network positive coupling; and State II that showed between-network connectivity, mostly involving somatomotor and visual networks. Sex differences were found in dynamic indexes in HC but these differences were not observed in PD. Hierarchical clustering analysis identified three phenotypically distinct PD subgroups: (1) Subgroup A was characterized by mild motor symptoms; (2) Subgroup B was characterized by depressive and motor symptoms; (3) Subgroup C was characterized by cognitive and motor symptoms. Results revealed that changes in the temporal properties of connectivity were related to the motor/non-motor outcomes of PD severity. Findings suggest that while in HC sex differences may play a certain role in dynamic connectivity patterns, in PD patients, these effects may be overcome by the neurodegenerative process. Changes in the temporal properties of connectivity in PD were mainly related to the clinical markers of PD severity.
Highlights
In the last few years, functional connectivity (FC) during restingstate functional magnetic resonance imaging has been used in Parkinson’s disease (PD) to study the neural mechanisms of various complications, such as cognitive impairment[1,2,3] and depression[4,5,6,7]
No significant sex differences were found in healthy controls (HC) and PD participants for cognition or clinical features between PD males and females
Cognition and depression were tested with a two-way multivariate analysis of covariance (MANCOVA)
Summary
In the last few years, functional connectivity (FC) during restingstate functional magnetic resonance imaging (rs-fMRI) has been used in Parkinson’s disease (PD) to study the neural mechanisms of various complications, such as cognitive impairment[1,2,3] and depression[4,5,6,7]. A number of studies have applied timevarying analysis methods for brain connectivity, known as dynamic FC, in diverse populations[8,9]. Dynamic FC alterations have been reported in the disease, showing changes in the number of state transitions, and reduced time spent in the sparsely connected state, linked to an increased time spent in the strongly between-network connected state[16]. These alterations have shown relationships with motor symptoms and various degrees of cognitive impairment[16,19,20]
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