Writer's cramp: increased dorsal premotor activity during intended writing

Abstract

Simple writer's cramp (WC) is a task-specific form of dystonia, characterized by abnormal movements and postures of the hand during writing. It is extremely task-specific, since dystonic symptoms can occur when a patient uses a pencil for writing, but not when it is used for sharpening. Maladaptive plasticity, loss of inhibition, and abnormal sensory processing are important pathophysiological elements of WC. However, it remains unclear how those elements can account for its task-specificity. We used fMRI to isolate cerebral alterations associated with the task-specificity of simple WC. Subjects (13 simple WC patients, 20 matched controls) imagined grasping a pencil to either write with it or sharpen it. On each trial, we manipulated the pencil's position and the number of imagined movements, while monitoring variations in motor output with electromyography. We show that simple WC is characterized by abnormally increased activity in the dorsal premotor cortex (PMd) when imagined actions are specifically related to writing. This cerebral effect was independent from the known deficits in dystonia in generating focal motor output and in processing somatosensory feedback. This abnormal activity of the PMd suggests that the task-specific element of simple WC is primarily due to alterations at the planning level, in the computations that transform a desired action outcome into the motor commands leading to that action. These findings open the way for testing the therapeutic value of interventions that take into account the computational substrate of task-specificity in simple WC, e.g. modulations of PMd activity during the planning phase of writing.

Figure 1

Time course of motor imagery trials. During each trial, after inspection of the picture on display, the subjects closed their eyes and pressed a button with the index finger of their left hand to signal they had started imagining to grasp the pencil for writing or sharpening it. During the sharpening task, a pencil and a handheld sharpener were shown (A). During the writing task, a pencil and a blank piece of paper were shown (B). The pencil was shown in two orientations that afforded either a biomechanically difficult (A) or easy (B) movement. The subjects pressed the button again when they finished imagining writing or sharpening the pencil according to the number of movement repetitions (0×, 2×, 4×, 6×) stated in the visual instructions. Following the second button press, a fixation cross was presented on the screen and the subjects could open their eyes. After a variable intertrial interval (ITI, intertrial interval, 3–5 s) a new picture was shown. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Figure 2

Behavioural performance during scanning. This figure illustrates the imagery times (IT) measured in trials involving (A) different movement repetitions (0, 2, 4, and 6) and (B) different biomechanical constraints (easy, difficult) separately for each task (write, sharpen) and group (controls, patients).

Figure 3

Differential cerebral effects of imagined writing in patients and controls. Panel A shows cerebral activity that increased during motor imagery of writing vs. motor imagery of sharpening, and more in patients than in controls. This contrast is shown at an uncorrected threshold of P < 0.05 and P < 0.01 (for graphical purposes), overlaid onto the structural scan of a representative subject from the MNI series. To restrict these effects to areas specifically involved in motor imagery, we included only voxels where activity increased linearly with repetition (2, 4, or 6 imagined movements) and where activity increased more for biomechanically difficult than easy trials (using inclusive masking at an uncorrected threshold of P < 0.05). The left side of the figure is the left side of the brain. Panel B shows cerebral responses over the left dorsal premotor cortex (PMd; −24 −6 +66]. This region showed a significant Group × Task interaction (P = 0.048, FDR‐corrected). For each group, the histograms show parameter estimates (in S.E.M. units) evoked by writing (the left two bars for each group) or sharpening (the right two bars for each group), separately for trials involving biomechanically easy movements (dark gray bars) or biomechanically difficult movements (light gray bars). Effects are averaged over the different repetitions (2, 4, or 6 imagined movements). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]