Advanced structural and functional MRI techniques in Parkinson’s Disease

Parkinson disease (PD) is clinically characterized by resting tremor, rigidity and bradykinesia, and its neuropathological hallmark is degeneration of dopaminergic cells in the substantia nigra (SN). However, PD is associated with several non-motor signs and symptoms and with widespread neuropathologic abnormalities in other non-dopaminergic chemical systems such as the cholinergic and serotoninergic neurotransmission. Visual assessment of conventional MRI has limited application in the evaluation of patients with PD, and it has been utilized mainly to confirm or exclude secondary parkinsonisms. However, advanced MRI techniques including MR morphometry, diffusion MR imaging and functional MRI (fMRI) have provided relevant quantitative information for improved understanding of the structural and functional abnormalities underlying neurodegenerative disorders as PD. MR morphometry studies show regions of selective gray matter (GM) atrophy of the cerebral cortex of PD patients in advanced clinical stages that are more extensive in patients with dementia. Diffusion tensor imaging parameters such as mean diffusivity (MD) and fractional anisotropy (FA) are sensitive to early microstructural changes of the nervous tissue. Moreover, fiber tracking analyses can be employed to dissect in vivo the major bundles of fibers connecting different brain areas. FA or MD changes in the SN and related white matter tracts as well as in GM regions have been shown in some studies of PD patients, along with decreased structural connectivity between SN and putamen-thalamus. fMRI has been used to investigate abnormalities in patterns of regional brain activation during a variety of motor and cognitive tasks. The results of these studies have demonstrated that PD patients can display a complex pattern of cortical activation, with both hypo- and hyperactive areas with respect to healthy controls. Hypoactivation is thought to represent an effect of cortical de-afferentation due to an impaired basal ganglia outflow, while hyperactivation is assumed either to reflect a compensatory reorganization of the nervous system or to be an expression of neurological dysfunction. Resting-state fMRI studies enable to measure functional connectivity during spontaneous brain activity. Some pilot studies have suggested that PD is associated with a specific pattern of functional connectivity dysfunction and have highlighted the importance of considering PD as a disease that influence large-scale networks, rather than single brain regions.