Abnormal functional connectivity density involvement in freezing of gait and its application for subtyping Parkinson's disease

The pathophysiological mechanisms at work in Parkinson's disease (PD) patients with freezing of gait (FOG) remain poorly understood. Functional connectivity density (FCD) could provide an unbiased way to analyse connectivity across the brain. In this study, a total of 23 PD patients with FOG (PD FOG + patients), 26 PD patients without FOG (PD FOG- patients), and 22 healthy controls (HCs) were recruited, and their resting-state functional magnetic resonance imaging (rs-fMRI) images were collected. FCD mapping was first performed to identify differences between groups. Pearson correlation analysis was used to explore relationships between FCD values and the severity of FOG. Then, a machine learning model was employed to classify each pair of groups. PD FOG + patients showed significantly increased short-range FCD in the precuneus, cingulate gyrus, and fusiform gyrus and decreased long-range FCD in the frontal gyrus, temporal gyrus, and cingulate gyrus. Short-range FCD values in the middle temporal gyrus and inferior temporal gyrus were positively correlated with FOG questionnaire (FOGQ) scores, and long-range FCD values in the middle frontal gyrus were negatively correlated with FOGQ scores. Using FCD in abnormal regions as input, a support vector machine (SVM) classifier can achieve classification with good performance. The mean accuracy values were 0.895 (PD FOG + vs. HC), 0.966 (PD FOG- vs. HC), and 0.897 (PD FOG + vs. PD FOG-). This study demonstrates that PD FOG + patients showed altered short- and long-range FCD in several brain regions involved in action planning and control, motion processing, emotion, cognition, and object recognition.

Automated summary

The pathophysiological mechanisms of freezing of gait (FOG) in Parkinson's disease (PD) patients are not well understood. Functional connectivity density (FCD) can be used to analyze connectivity across the brain in an unbiased way. This study found that PD FOG + patients had increased short-range FCD in certain brain regions and decreased long-range FCD in others. Short-range FCD values in the middle temporal gyrus and inferior temporal gyrus were positively correlated with FOG severity, while long-range FCD values in the middle frontal gyrus were negatively correlated. A machine learning model achieved good classification performance using FCD in abnormal regions. Overall, this study demonstrates altered FCD patterns in PD FOG + patients.