Neural correlates of bradykinesia in Parkinson's disease: a kinematic and functional MRI study

Abstract

Bradykinesia is defined as a "complex" of motor alterations including decreased movement amplitude and/or speed and tendency to reduce them with movement repetition (sequence effect). This study aimed at investigating the neural and kinematic correlates of bradykinesia during hand-tapping in people with Parkinson's disease (pwPD) relative to healthy controls. Twenty-five pwPD and 25 age- and sex-matched healthy controls underwent brain functional MRI (fMRI) during a hand-tapping task: subjects alternatively opened and closed their right hand as fully and quickly as possible. Hand-tapping kinematic parameters were objectively measured during the fMRI task using an optical fibre glove. During the fMRI task, pwPD showed reduced hand-tapping amplitude (hypokinesia) and a greater sequence effect. PwPD relative to healthy controls showed a reduced activity of fronto-parietal areas, middle cingulum/supplementary motor area (SMA), parahippocampus, pallidum/thalamus and motor cerebellar areas. Moreover, pwPD showed an increased activity of brain cognitive areas such as superior temporal gyrus, posterior cingulum, and cerebellum crus I. The decreased activity of cerebellum IV-V-VI, vermis IV-V, inferior frontal gyrus, and cingulum/SMA correlated with hypokinesia and with the sequence effect. Interestingly, a reduced activity of areas involved in motor planning and timing correlated both with hypokinesia and with the sequence effect in pwPD. This study has the major strength of collecting objective motor parameters and brain activity simultaneously, providing a unique opportunity to investigate the neural correlates of the "bradykinesia complex".

Fig. 1. Kinematic parameters assessed with 5DT Data Glove during the fMRI hand-tapping task with the right hand in HC and pwPD.

Box plot centre line refers to median; box limits refer to first and third quartiles; whiskers refer to minimum and maximum values. p values refer to Mann–Whitney test. Statistical significance: p < 0.05. HC healthy controls, pwPD people with Parkinson’s Disease, s seconds.

Fig. 2. FMRI differences between pwPD and healthy controls during the right hand-tapping task.

All findings are shown at p < 0.001 uncorrected (5000 permutations), only cluster >5 voxels are reported. Colour bars denote T value. Results are shown on axial, sagittal and coronal sections (z, x or y MNI coordinates are reported) of the Montreal Neurological Institute standard template. fMRI functional Magnetic Resonance Imaging, HC healthy controls, L left, pwPD people with Parkinson’s Disease, R right.

Fig. 3. Correlation between fMRI and kinematic data obtained during the right hand-tapping task.

Correlations in pwPD (A) and in pwPD and healthy controls together (B). All findings are shown at p < 0.001 uncorrected (5000 permutations). Colour bars denote T value. Results are shown on axial, sagittal and coronal sections (z, x or y MNI coordinates are reported) of the Montreal Neurological Institute standard template. r and p refer to Spearman’s correlation coefficient. fMRI functional Magnetic Resonance Imaging, HC healthy controls, L left, pwPD people with Parkinson’s Disease, R right.