Neural substrates of motor and non-motor symptoms in Parkinson's disease: a resting FMRI study

Abstract

Background: Recently, non-motor symptoms of Parkinson's disease (PD) have been considered crucial factors in determining a patient's quality of life and have been proposed as the predominant features of the premotor phase. Researchers have investigated the relationship between non-motor symptoms and the motor laterality; however, this relationship remains disputed. This study investigated the neural connectivity correlates of non-motor and motor symptoms of PD with respect to motor laterality.

Methods: Eight-seven patients with PD were recruited and classified into left-more-affected PD (n = 44) and right-more affected PD (n = 37) based on their MDS-UPDRS (Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale) motor examination scores. The patients underwent MRI scanning, which included resting fMRI. Brain regions were labeled as ipsilateral and contralateral to the more-affected body side. Correlation analysis between the functional connectivity across brain regions and the scores of various symptoms was performed to identify the neural connectivity correlates of each symptom.

Results: The resting functional connectivity centered on the ipsilateral inferior orbito-frontal area was negatively correlated with the severity of non-motor symptoms, and the connectivity of the contralateral inferior parietal area was positively correlated with the severity of motor symptoms (p < 0.001, |r| > 0.3).

Conclusions: These results suggest that the inferior orbito-frontal area may play a crucial role in non-motor dysfunctions, and that the connectivity information may be utilized as a neuroimaging biomarker for the early diagnosis of PD.

Fig 1. Functional connectivity correlated with the MDS-UPDRS part I score.

The inferior orbito-frontal area in the ipsilateral hemisphere has substantial functional connectivity negatively correlated with the severity of non-motor symptoms. Other ipsilateral inferior frontal areas such as the pars triangularis and the anterior cingulate cortex also exhibit functional connectivity correlated with the severity of non-motor symptoms. (p<0.001) (Blue line: a functional connectivity negatively correlated with the MDS-UPDRS part I score; C: contralateral hemisphere & I: ipsilateral hemisphere; MDS-UPDRS: Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale)

Fig 2. Functional connectivity correlated with the MDS-UPDRS part II score.

Limited functional connectivity is shown to correlate with the MDS-UPDRS part II score. This score positively correlates with the functional connectivity between the pars triangularis and the orbital part of the medial frontal gyrus within the ipsilateral hemisphere, and with the connectivity between ipsilateral inferior parietal lobule and contralateral middle temporal pole. The MDS-UPDRS part II has a negative correlation with the connectivity between rectal gyrus and the fusiform gyrus in the contralateral hemisphere. (p<0.001) (Blue line: a functional connectivity negatively correlated with the MDS-UPDRS part II score & red line: a functional connectivity positively correlated with the MDS-UPDRS part II score; C: contralateral hemisphere & I: ipsilateral hemisphere; MDS-UPDRS: Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale)

Fig 3. Functional connectivity correlated with the MDS-UPDRS part III score.

The inferior parietal area in the contralateral hemisphere has substantial functional connectivity positively correlated with the severity of motor symptoms. The contralateral postcentral gyrus also exhibits functional connectivity positively correlated with the severity of motor symptoms. Connectivity between the pars triangularis and the orbital part of the medial frontal gyrus is also positively correlated with the MDS-UPDRS part III score, whereas the connectivity of bilateral rectus gyri is negatively correlated with this score. (p<0.001) (Blue line: a functional connectivity negatively correlated with the MDS-UPDRS part III score & red line: a functional connectivity positively correlated with the MDS-UPDRS part III score; C: contralateral hemisphere & I: ipsilateral hemisphere; MDS-UPDRS: Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale)

Fig 4. Functional connectivity correlated with the S&E ADL score.

The functional connectivity between the Rolandic operculum and the insula in the ipsilateral hemisphere and between the Rolandic operculum and the superior temporal gyrus in the contralateral hemisphere are positively correlated with the S&E ADL score. (p<0.001) (Red line: a functional connectivity positively correlated with the S&E ADL score; C: contralateral hemisphere & I: ipsilateral hemisphere; S&E ADL: Schwab and England activities of daily living).