Abnormal Movement Preparation in Task-Specific Focal Hand Dystonia

<div><p>Electrophysiological and behavioral studies in primary dystonia suggest abnormalities during movement preparation, but this crucial phase preceding movement onset has not yet been studied specifically with functional magnetic resonance imaging (fMRI). To identify abnormalities in brain activation during movement preparation, we used event-related fMRI to analyze behaviorally unimpaired sequential finger movements in 18 patients with task-specific focal hand dystonia (FHD) and 18 healthy subjects. Patients and controls executed self-initiated or externally cued prelearnt four-digit sequential movements using either right or left hands. In FHD patients, motor performance of the sequential finger task was not associated with task-related dystonic posturing and their activation levels during motor execution were highly comparable with controls. On the other hand reduced activation was observed during movement preparation in the FHD patients in left premotor cortex / precentral gyrus for all conditions, and for self-initiation additionally in supplementary motor area, left mid-insula and anterior putamen, independent of effector side. Findings argue for abnormalities of early stages of motor control in FHD, manifesting during movement preparation. Since deficits map to regions involved in the coding of motor programs, we propose that task-specific dystonia is characterized by abnormalities during recruitment of motor programs: these do not manifest at the behavioral level during simple automated movements, however, errors in motor programs of complex movements established by extensive practice (a core feature of FHD), trigger the inappropriate movement patterns observed in task-specific dystonia.</p> </div

Between-group Activation Changes during Preparation of Movements.

<p>Decreased activity in patients (FHD) compared to controls (CONTR) during motor preparation (PREP). p<.001 (uncorrected), extent threshold 10 voxel. Right hand (red), left hand (yellow). <b>A</b>: Self-initiated <b>B</b>: Externally cued <b>C</b>: Reduced self-initiation-related activity (white: p<0.005). Note effector independent distributions. Coordinates shown (x, y, z) are in MNI-space.</p

Experimental Paradigm.

<p><b>A</b>: Experimental paradigm (trial). Black arrow: finger sequence. React-condition (upper bar): movement onset is delayed with respect to the cue (green). Free-condition (lower bar): movement onset triggers color change (green). <b>B</b>: Phases modeled for data analysis: preparation (PREP), execution (EXE).</p

Main effects of laser pain stimulation in PD patients.

<p>Main effects of laser pain stimulation in PD patients.</p

Behavioral data evoked by laser-induced pain stimulation.

<p>Behavioral data evoked by laser-induced pain stimulation.</p

Between group effects (PD vs. HC) for the HPS condition.

<p>Between group effects (PD vs. HC) for the HPS condition.</p

Central activation for the LPS and HPS pain condition in early-stage PD and healthy controls.

<p>Central activation (p < 0.05, FWE cluster corrected) in early-stage PD patients (A, C) and healthy controls (B, D) for the LPS (A, B) and HPS (C, D) condition. For activated regions see also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0164607#pone.0164607.t003" target="_blank">Table 3</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0164607#pone.0164607.t004" target="_blank">Table 4</a>. HC: healthy controls, HPS: high pain laser stimulus with higher target energy (E = 600 mJ), LPS: low pain laser stimulus with lower target energy (E = 440 mJ), PD: patients with early-stage Parkinson’s disease in OFF state.</p

Within-group Activity during Preparation of Movements.

<p>Within-group activity during preparation of movements in healthy control subjects (CONTR; A and C) and focal hand dystonia patients (FHD; B and D). Activation during motor preparation (PREP) of self-initiated (Free; A and B) and externally cued (React; <b>C</b> and <b>D</b>) conditions. Voxels surpassing a height threshold of p < 0.001 (FDR-corrected) and an extent threshold (cluster size) of k=10 are superimposed on the MNI-T1-template of SPM5, and color coded for right hand (red), left hand (green) and common activations (overlay; yellow). Coordinates shown (x, y, z) are in MNI-space.</p

Main effects of laser pain stimulation in healthy control subjects.

<p>Main effects of laser pain stimulation in healthy control subjects.</p

Procedure of subject recruitment and pain imaging study.

<p>Subject recruitment included a first telephone interview and was followed by a first visit for an electroneurographic polyneuropathy screening. At a second visit enrolled subjects underwent the experimental pain study, consisting of psychological questionnaires, clinical tests, quantitative sensory testing, event related fMRI, and behavioral pain testings.</p