The cerebellum in Parkinson's disease

Abstract

Parkinson's disease is a chronic progressive neurodegenerative disorder characterized by resting tremor, slowness of movements, rigidity, gait disturbance and postural instability. Most investigations on Parkinson's disease focused on the basal ganglia, whereas the cerebellum has often been overlooked. However, increasing evidence suggests that the cerebellum may have certain roles in the pathophysiology of Parkinson's disease. Anatomical studies identified reciprocal connections between the basal ganglia and cerebellum. There are Parkinson's disease-related pathological changes in the cerebellum. Functional or morphological modulations in the cerebellum were detected related to akinesia/rigidity, tremor, gait disturbance, dyskinesia and some non-motor symptoms. It is likely that the major roles of the cerebellum in Parkinson's disease include pathological and compensatory effects. Pathological changes in the cerebellum might be induced by dopaminergic degeneration, abnormal drives from the basal ganglia and dopaminergic treatment, and may account for some clinical symptoms in Parkinson's disease. The compensatory effect may help maintain better motor and non-motor functions. The cerebellum is also a potential target for some parkinsonian symptoms. Our knowledge about the roles of the cerebellum in Parkinson's disease remains limited, and further attention to the cerebellum is warranted.

Figure 1

Structural connections between the basal ganglia and cerebellum. The solid line indicates the projection from the dentate nucleus to the striatum, while the dotted line indicates the projection from the subthalamic nucleus to the cerebellar cortex. STN = subthalamic nucleus. Information fromBostanet al. (2010).

Figure 2

Brain areas more activated in patients with Parkinson’s disease than in normal subjects during automatic execution of sequential movements. Modified fromWu and Hallett (2005), with permission from Oxford University Press.

Figure 3

Tremor-related cerebral activity in tremor-dominant Parkinson’s disease. Location of cerebral regions where activity cofluctuated with tremor amplitude. Activity was localized to the motor cortex, ventral intermediate nucleus of the thalamus and cerebellum (side contralateral to the tremor). BA = Brodmann area; lob = lobule; VIM = ventral intermediate nucleus. Reprinted fromHelmichet al. (2011), with permission from John Wiley and Sons.

Figure 4

Relative underactivity (A) and overactivity (B) induced by treadmill walking in patients with Parkinson’s disease. InA, relative underactivity in Parkinson’s disease includes the left cerebellar hemisphere (1), precuneus (2) and the left presupplementary motor cortex (3). InB, relative overactivity in Parkinson’s disease was found in the left middle temporal gyrus (1), right insula (2), left cingulate cortex (3) and cerebellar vermis (4 and 5). Modified fromHanakawaet al. (1999), with permission from Oxford University Press.

Figure 5

Increased mean diffusivity in bilateral orbitofrontal cortices (A) and bilateral inferior temporal gyri (B), decreased mean diffusivity in bilateral parietal lobes and left precentral gyrus (C) and decreased fractional anisotropy in bilateral cerebellum and right rectus gyrus (D) in patients with Parkinson’s disease versus normal controls. The red colour indicates an increase of the value, and blue-green colour indicates a decrease. Modified fromZhanget al. (2011), with permission from Elsevier.

Figure 6

A hypothetical model of functional changes in the cerebellum accompanying the progression of Parkinson’s disease.