The cerebral mechanisms underlying dystonic and essential tremor: a multimodal network approach

Tremor is often the presenting and most bothersome symptom of dystonia,
occurring in 17-55% of patients. In patients with dystonia, tremor may involve
the dystonic limb but also other body parts. Here we will define *dystonic
tremor* (DT) as an umbrella term for both tremor types. There is a high risk of
misdiagnosing DT, due to substantial clinical overlap with essential tremor
(ET), and because disease markers are lacking. Also, there are no treatments
specifically targeting DT, so most clinicians follow a trial-and-error approach
- often with unsatisfactory results. Lack of knowledge on the pathophysiology
of DT hampers the development of new, mechanism-based interventions. Here we
build on recent circumstantial evidence suggesting different circuit-level
alterations in DT and ET. Namely, while both the basal ganglia and the
cerebello-thalamic circuit may be involved in DT, the cerebellum - but not the
basal ganglia - is thought to play a primary role in ET.

We aim to identify the circuit-level cerebral mechanisms underlying DT, and
separate them from those involved in ET. Furthermore, we test whether a
non-invasive intervention in this circuit (applied to the motor cortex or
cerebellum) can differentially impact on both tremor types. We hypothesize that
DT results from an abnormal interplay between basal ganglia and the
cerebello-thalamo-cortical circuit, while ET is primarily driven by abnormal
cerebellar activity.

combined cross-sectional and exploratory intervention study

The intervention involves transcranial alternating current stimulation (TACS),
which is a non-invasive, non-painful way of stimulating underlying cortical
brain tissue through electrodes applied to the scalp. When applied rhythmically
at the frequency of cortical oscillatory activity, it can exert powerful
excitatory or inhibitory (depending on the phase) effects on brain function.

The load on patients consists of the time spent on this project (2 visits), and
potentially a temporary worsening of dystonic symptoms caused by withholding
medication on the morning before assessments. All measurements are
non-invasive, painless, and without nuclear radiation. Individual participants
do not directly benefit from participation. However, we expect that this study
will improve our knowledge about the cerebral mechanisms underlying DT and ET
and may lead to new ways of diagnosing and perhaps treating these disorders.