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Differences in Brain Activation Between Tremor- and Nontremor-Dominant Parkinson Disease

Janey Prodoehl, PhD; Peggy J. Planetta, PhD; Ajay S. Kurani, MS; Cynthia L. Comella, MD; Daniel M. Corcos, PhD; David E. Vaillancourt, PhD
JAMA Neurol. 2013;70(1):100-106. doi:10.1001/jamaneurol.2013.582.
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Objective  To compare differences in functional brain activity between tremor- and nontremor-dominant subtypes of Parkinson disease (PD) using functional magnetic resonance imaging.

Design  In our study, patients with tremor-dominant PD and those with nontremor-dominant PD performed a grip task, and the results obtained were compared using voxelwise analysis. Areas of the brain that were significantly different were then examined using a region-of-interest analysis to compare these patients with healthy controls. Voxel-based morphometry was used to determine macroscopic differences in gray and white matter volume between patient groups.

Setting  University-affiliated research institution.

Participants  A total of 20 drug-naive patients with PD (10 with tremor-dominant PD and 10 with nontremor-dominant PD) and a total of 20 healthy controls.

Main Outcome Measures  Blood oxygenation level–dependent activation and percent signal change.

Results  Robust findings across both voxelwise and region-of-interest analyses showed that, compared with patients with tremor-dominant PD, patients with nontremor-dominant PD had reduced activation in the ipsilateral dorsolateral prefrontal cortex, the globus pallidus interna, and the globus pallidus externa. Region-of-interest analyses confirmed that patients with nontremor-dominant PD had reduced activity in the ipsilateral dorsolateral prefrontal cortex, the globus pallidus interna, and the globus pallidus externa compared with patients with tremor-dominant PD and healthy controls. Patients with tremor-dominant PD had increased activity in the contralateral dorsolateral prefrontal cortex compared with patients with nontremor-dominant PD and healthy controls. These results could not be explained by differences in gray or white matter volume.

Conclusions  Reduced brain activity occurs in the prefrontal cortex and globus pallidus of patients with nontremor-dominant PD compared with both patients with tremor-dominant PD and healthy controls, which suggests that functional magnetic resonance imaging is a promising technique to understand differences in brain activation between subtypes of PD.

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Figures

Place holder to copy figure label and caption
Grahic Jump Location

Figure 1. A, Grip force transducer used to produce isometric force and visual display seen by the participant at rest (red bar) and during force production (green bar). B, Representative force traces from a patient with tremor-dominant PD (TD; left) and a patient with nontremor-dominant PD (NTD; right).The functional magnetic resonance imaging experiment was a block-design paradigm of four 30-second task blocks and five 30-second rest blocks. During rest blocks, the participants fixated on a stationary red target without producing force. During task blocks, the participants performed 2-second pulse-hold contractions followed by 1 second of rest. The target bar represented 15% of the maximum voluntary contraction (MVC). A white cursor on the screen moved vertically and was related to the force produced by the participant.

Place holder to copy figure label and caption
Grahic Jump Location

Figure 2. Brain activation in tremor-dominant (TD) and nontremor-dominant (NTD) groups of patients with Parkinson disease (PD). Voxelwise analysis of TD minus NTD groups was performed using AFNI software. A, Reduced activity in the inferior parietal lobule (IPL), the bilateral dorsolateral prefrontal cortex (DLPFC), and the pre–supplementary motor area (pre-SMA) in NTD patients with PD compared with TD patients with PD. B, Color-coded Basal Ganglia Human Area Template16 that was used to identify the location of basal ganglia activation (top panel). Reduced activation is shown for the contralateral caudate (green circle), the globus pallidus externa (GPe; red circle), the globus pallidus interna (GPi; orange circle), and the ipsilateral thalamus in NTD patients with PD compared with TD patients with PD. C, Percent signal change (PSC) in controls, TD patients, and NTD patients in the contralateral and ipsilateral DLPFC (top) and in the GPi and GPe (bottom). STN indicates subthalamic nucleus.

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