Functional connectivity of the cortico-subcortical sensorimotor loop is modulated by the severity of nigrostriatal dopaminergic denervation in Parkinson’s Disease

Abstract

To assess if the severity of nigrostriatal innervation loss affects the functional connectivity (FC) of the sensorimotor cortico-striato-thalamic-cortical loop (CSTCL) in Parkinson’s Disease (PD), Resting-State functional MRI and 18F-DOPA PET data, simultaneously acquired on a hybrid PET/MRI scanner, were retrospectively analyzed in 39 PD and 16 essential tremor patients. Correlations between posterior Putamen DOPA Uptake (pPDU) and the FC of the main CSTCL hubs were assessed separately in the two groups, analyzing the differences between the two groups by a group-by-pPDU interaction analysis of the resulting clusters’ FC. Unlike in essential tremor, in PD patients pPDU correlated inversely with the FC of the thalamus with the sensorimotor cortices, and of the postcentral gyrus with the dorsal cerebellum, and directly with the FC of pre- and post-central gyri with both the superior and middle temporal gyri and the paracentral lobule, and of the caudate with the superior parietal cortex. The interaction analysis confirmed the significance of the difference between the two groups in these correlations. In PD patients, the post-central cortex FC, in the clusters correlating directly with pPDU, negatively correlated with both UPDRS motor examination score and Hoehn and Yahr stage, independent of the pPDU, suggesting that these FC changes contribute to motor impairment. In PD, nigrostriatal innervation loss correlates with a decrease in the FC within the sensorimotor network and between the sensorimotor network and the superior temporal cortices, possibly contributing to motor impairment, and with a strengthening of the thalamo-cortical FC, that may represent ineffective compensatory phenomena.

Altered brain connectivity in hyperkinetic movement disorders: A review of resting-state fMRI

“…( Bagarinao et al, 2022 ) Finally, a study assessed if the severity of nigrostriatal innervation loss affects the FC of the sensorimotor cortico-striatothalamic-cortical loop in ET and PD. ( Quarantelli et al, 2022 ) This was not the case in ET, whereas in PD patients the putamen dopamine intake showed an inverse correlation with the FC of thalamus and cerebellum with sensorimotor cortices.…”

“…The 51 included articles on tremor concerned tremor-dominant Parkinson’s disease (TDPD; n = 28), essential tremor (ET; n = 21), orthostatic tremor (n = 2), and primary writing tremor (n = 1). ( Bagarinao et al, 2022 , Basaia et al, 2022 , Benito-Leon et al, 2015 , Benito-Leon et al, 2016 , Benito-Leon et al, 2019 , Chen et al, 2015 , Chen et al, 2019 , Dirkx et al, 2017 , Dirkx et al, 2019 , Duan et al, 2021 , Fang et al, 2013 , Fang et al, 2015 , Fang et al, 2016 , Gallea et al, 2015 , Gallea et al, 2016 , Gu et al, 2017 , Helmich et al, 2011 , Hou et al, 2018 , Hu et al, 2015 , Hu et al, 2017 , Hu et al, 2019 , Jiang et al, 2016 , Karunanayaka et al, 2016 , Kato et al, 2022 , Lenka et al, 2017 , Lenka et al, 2017 , Li et al, 2018 , Li et al, 2020 , Li et al, 2021 , Li et al, 2021 , Ma et al, 2015 , Ma et al, 2017 , Mueller et al, 2017 , Nicoletti et al, 2020 , Nigro et al, 2019 , Popa et al, 2013 , Quarantelli et al, 2022 , Tikoo et al, 2020 , Tuleasca et al, 2018 , Tuleasca et al, 2020 , Vervoort et al, 2016 , Wang et al, 2016 , Wang et al, 2018 , Wang et al, 2021 , Wen et al, 2016 , Yin et al, 2016 , Zhang et al, 2015 , Zhang et al, 2015 , Zhang et al, 2015 , Zhang et al, 2016 , Zhu et al, 2021 ) The number of patients per study ranged from 10 to 99.…”

A systematic review of the challenges, emerging solutions and applications, and future directions of PET/MRI in Parkinson’s disease

“…Small population numbers have been reported to lower the ability to detect differences between PD and other similar disorders (thereby not useful for disease differentiation during clinical diagnosis) (Biundo et al 2021 ; Garon et al 2022 ; Shang et al 2021b ). On the other hand, two other studies found that the small sample size restricted the ability to examine multiple brain regions (therefore potentially missing important ROIs and global changes for disease staging within a clinical setting) (Quarantelli et al 2022 ; Rodriguez-Rojas et al 2020 ).…”

“…This may be due to expensive machinery, operational costs, and lack of trained expertise (Vitor et al 2017a ; Wimalarathne et al 2022 ; Mangalore et al 2022 ). It is also questionable as to whether it is even necessary to use PET/MRI, as one study has raised the concern that a limitation to their study was the lack of a healthy control to avoid unnecessary exposure to ionising radiation (Quarantelli et al 2022 ). Until more large-scale, robust, and longitudinal studies are conducted using PET/MRI, PET/CT is the more accepted hybrid system to simultaneously acquire metabolic and structural information due to its widespread availability (despite also including exposure to ionising radiation).…”

Drooling disrupts the brain functional connectivity network in Parkinson's disease

“…The major cause of drooling in PD patients is swallowing dysfunction in the oral and/or pharyngeal phase of swallowing, which is also a manifestation of motor difficulties in PD 4 . It is reported that motor difficulties in PD are attributed to sensorimotor dysfunction caused by denervation along the cortex‐striatum pathway following nigrostriatal dopaminergic loss 8–10 . Thus, the occurrence of drooling in PD patients is closely associated with sensorimotor areas of the brain.…”