Distinct functional and macrostructural brain changes in Parkinson's disease and multiple system atrophy

Abstract

Parkinson’s disease (PD) and the parkinsonian variant of multiple system atrophy (MSAp) are neurodegenerative disorders that can be difficult to differentiate clinically. This study provides the first characterization of the patterns of task-related functional magnetic resonance imaging (fMRI) changes across the whole brain in MSAp. We used fMRI during a precision grip force task and also performed voxel-based morphometry (VBM) on T1-weighted images in MSAp patients, PD patients, and healthy controls. All groups were matched on age, and the patient groups had comparable motor symptom durations and severities. There were three main findings. First, MSAp and PD had reduced fMRI activation in motor control areas, including the basal ganglia, thalamus, insula, primary sensorimotor and prefrontal cortices, and cerebellum compared with controls. Second, there were no activation differences among the disease groups in the basal ganglia, thalamus, insula, or primary sensorimotor cortices, but PD had more extensive activation deficits throughout the cerebrum compared with MSAp and controls. Third, VBM revealed reduced volume in the basal ganglia, middle and inferior cerebellar peduncles, pons, and throughout the cerebrum in MSAp compared with controls and PD, and additionally throughout the cerebellar cortex and vermis in MSAp compared with controls. Collectively, these results provide the first evidence that fMRI activation is abnormal in the basal ganglia, cerebellum, and cerebrum in MSAp, and that a key distinguishing feature between MSAp and PD is the extensive and widespread volume loss throughout the brain in MSAp.

Free‐water and BOLD imaging changes in Parkinson's disease patients chronically treated with a MAO‐B inhibitor

“…The fMRI protocol consisted of a block-design that alternated force and rest blocks as follows: 30 s rest, 30 s force with performance feedback, 12.5 s rest, and 30 s force without performance feedback [Burciu et al, 2015; Neely et al, 2014; Planetta et al, 2014; Prodoehl et al, 2010; Spraker et al, 2010]. This sequence was repeated four times and there was an additional 30-s rest period following the final block of force without performance feedback.…”

Diagnosis of multiple system atrophy

“…Acquisition of fMRI is usually performed during specific tasks (e.g., motor tasks). Motor control studies using fMRI engage an extensive task-related network including the basal ganglia, cerebellum, and motor cortex in healthy subjects, and defective activation of these structures in PD, MSA and PSP (Planetta et al, 2015). A study assessing longitudinal fMRI changes over the course of 1-year in PD, MSA, and PSP using a hand-grip-force paradigm showed reduced fMRI signal and more widespread and more pronounced changes in basal ganglia, cerebellum, and motor cortex in patients with MSA and PSP compared to PD (Burciu et al, 2016).…”

Sensory and motor cortex function contributes to symptom severity in spinocerebellar ataxia type 6

“…1a) because previous studies have shown reliable blood oxygen level-dependent (BOLD) activity changes in individuals with neurological disorders that include Parkinson’s disease, essential tremor, multiple system atrophy, and progressive supranuclear palsy (Burciu et al 2015; Neely et al 2015; Planetta et al 2015a; Spraker et al 2010). Further, our pilot data confirmed that SCA6 patients were able to execute pinch grip force with similar behavioral performance as age-matched healthy controls.…”

“…In the no vision block, the green bar did not move, and the subject had to produce the force from memory. We did not have a specific hypothesis for the vision and no vision blocks, and we used this paradigm because it is well-validated in prior studies and the paradigm elicits a robust BOLD signal across the cortex, basal ganglia, thalamus, and cerebellum (Burciu et al 2015; Neely et al 2015; Planetta et al 2015a). Participants completed eight total blocks (four vision and four no-vision) during the fMRI session.…”

“…Using a grip force control fMRI paradigm (Neely et al 2015; Planetta et al 2015a; Spraker et al 2010), we explored task-based fMRI activity within sensory and motor cortex and cerebellum, and task-based functional connectivity between cortical motor regions (i.e., sensorimotor cortex and supplementary motor area: SMA) and cerebellum. In addition, free-water diffusion magnetic resonance imaging (dMRI) was assessed using a bi-tensor model to evaluate the tissue compartment and the free-water compartment within cerebellar regions (i.e., dentate, cerebellar lobules V and VI, cerebellar vermis, and peduncles).…”