Functional imaging correlates of akinesia in Parkinson's disease: Still open issues

Abstract

Akinesia is a major manifestation of Parkinson's disease (PD) related to difficulties or failures of willed movement to occur. Akinesia is still poorly understood and is not fully alleviated by standard therapeutic strategies. One reason is that the area of the clinical concept has blurred boundaries referring to confounded motor symptoms. Here, we review neuroimaging studies which, by providing access to finer-grained mechanisms, have the potential to reveal the dysfunctional brain processes that account for akinesia. It comes out that no clear common denominator could be identified across studies that are too heterogeneous with respect to the clinical/theoretical concepts and methods used. Results reveal, however, that various abnormalities within but also outside the motor and dopaminergic pathways might be associated with akinesia in PD patients. Notably, numerous yet poorly reproducible neural correlates were found in different brain regions supporting executive control by means of resting-state or task-based studies. This includes for instance the dorsolateral prefrontal cortex, the inferior frontal cortex, the supplementary motor area, the medial prefrontal cortex, the anterior cingulate cortex or the precuneus. This observation raises the issue of the multidimensional nature of akinesia. Yet, other open issues should be considered conjointly to drive future investigations. Above all, a unified terminology is needed to allow appropriate association of behavioral symptoms with brain mechanisms across studies. We adhere to a use of the term akinesia restricted to dysfunctions of movement initiation, ranging from delayed response to freezing or even total abolition of movement. We also call for targeting more specific neural mechanisms of movement preparation and action triggering with more sophisticated behavioral designs/event-related neurofunctional analyses. More work is needed to provide reliable evidence, but answering these still open issues might open up new prospects, beyond dopaminergic therapy, for managing this disabling symptom.

Keywords: Akinesia; Neuroimaging; PET; Parkinson's disease; fMRI.

Graphical abstract

Fig. 1

Flow chart of publication selection for review, following PRISMA guidelines (Liberati et al., 2009).

Fig. 2

Results of the neuroimaging studies using resting state approaches and comparing AR to HS subjects to assess the neural bases of akinesia. Arrows between two distinct brain regions indicate abnormal connectivity in seed-based functional connectivity studies. Studies assessing AR patients ON medication are indicated by red stars.

Fig. 3

Results of the neuroimaging studies using resting state approaches and comparing AR to TD subjects to assess the neural bases of akinesia. Arrows between two distinct brain regions indicate abnormal connectivity in seed-based functional connectivity studies. Studies assessing AR patients ON medication are indicated by red stars.

Fig. 4

Results of the neuroimaging studies using task-based approaches and comparing AR to HS subjects to assess the neural bases of akinesia. Studies assessing AR patients ON medication are indicated by red stars.