Network-level connectivity is a critical feature distinguishing dystonic tremor and essential tremor

Dystonia is a movement disorder characterized by involuntary muscle co-contractions that give rise to disabling movements and postures. A recent expert consensus labelled the incidence of tremor as a core feature of dystonia that can affect body regions both symptomatic and asymptomatic to dystonic features. We are only beginning to understand the neural network-level signatures that relate to clinical features of dystonic tremor. At the same time, clinical features of dystonic tremor can resemble that of essential tremor and present a diagnostic confound for clinicians. Here, we examined network-level functional activation and connectivity in patients with dystonic tremor and essential tremor. The dystonic tremor group included primarily cervical dystonia patients with dystonic head tremor and the majority had additional upper-limb tremor. The experimental paradigm included a precision grip-force task wherein online visual feedback related to force was manipulated across high and low spatial feedback levels. Prior work using this paradigm in essential tremor patients produced exacerbation of grip-force tremor and associated changes in functional activation. As such, we directly compared the effect of visual feedback on grip-force tremor and associated functional network-level activation and connectivity between dystonic tremor and essential tremor patient cohorts to better understand disease-specific mechanisms. Increased visual feedback similarly exacerbated force tremor during the grip-force task in dystonic tremor and essential tremor cohorts. Patients with dystonic tremor and essential tremor were characterized by distinct functional activation abnormalities in cortical regions but not in the cerebellum. We examined seed-based functional connectivity from the sensorimotor cortex, globus pallidus internus, ventral intermediate thalamic nucleus, and dentate nucleus, and observed abnormal functional connectivity networks in dystonic tremor and essential tremor groups relative to controls. However, the effects were far more widespread in the dystonic tremor group as changes in functional connectivity were revealed across cortical, subcortical, and cerebellar regions independent of the seed location. A unique pattern for dystonic tremor included widespread reductions in functional connectivity compared to essential tremor within higher-level cortical, basal ganglia, and cerebellar regions. Importantly, a receiver operating characteristic determined that functional connectivity z-scores were able to classify dystonic tremor and essential tremor with 89% area under the curve, whereas combining functional connectivity with force tremor yielded 94%. These findings point to network-level connectivity as an important feature that differs substantially between dystonic tremor and essential tremor and should be further explored in implementing appropriate diagnostic and therapeutic strategies.

Neural correlates of task-related changes in physiological tremor

Appropriate control of muscle contraction requires integration of command signals with sensory feedback. Sensorimotor integration is often studied under conditions in which muscle force is controlled with visual feedback. While it is known that alteration of visual feedback can influence task performance, the underlying changes in neural drive to the muscles are not well understood. In this study, we characterize the frequency content of force fluctuations and neural drive when production of muscle force is target guided versus self guided. In the self-guided condition, subjects performed isometric contractions of the first dorsal interosseous (FDI) muscle while slowly and randomly varying their force level. Subjects received visual feedback of their own force in order to keep contractions between 6% and 10% of maximum voluntary contraction (MVC). In the target-guided condition, subjects used a display of their previously generated force as a target to track over time. During target tracking, force tremor increased significantly in the 3–5 and 7–9 Hz ranges, compared with self-guided contractions. The underlying changes in neural drive were assessed by coherence analysis of FDI motor unit activity. During target-guided force production, pairs of simultaneously recorded motor units showed less coherent activity in the 3–5 Hz frequency range but greater coherence in the 7–9 Hz range than in the self-guided contractions. These results show that the frequency content of common synaptic input to motoneurons is altered when force production is visually guided. We propose that a change in stretch-reflex gain could provide a potential mechanism for the observed changes in force tremor and motor unit coherence.