Understanding and manipulating neural compensatory mechanisms in SCA3 patients

Dominantly inherited spinocerebellar ataxias (SCAs) are a clinically,
genetically, and pathologically heterogeneous group of neurodegenerative
disorders mainly affecting the cerebellum and its connections. SCA3 is the most
common genotype. This disorder gives rise to progressive difficulties of gait,
dexterity, speech and eye movements, and leads to immobility and loss of
independence. There is currently no treatment.
Own pilot data suggest that specific forms of training are able to induce
improvements in gait and balance. We think that this is due to cerebral
compensation. We wish to capture these compensatory mechanisms by means of
sophisticated MRI scans before and after this training. The future goal is to
find ways to further stimulate such compensatory mechanisms as a form of
treatment.

We expect to isolate system-level neural mechanisms that support compensation
for gait and balance in patients with SCA3 following an intensive five-week
training programme on a virtual reality treadmill. The goal of the project is
to understand whether the behavioral improvements observed in SCA3 patients
after the training programme are supported by cerebral circuits directly
targeted by the neurodegenerative process, or by system-level reorganization
across vicarious cerebral circuits that support the same function. We will
consider three types of changes that have proven sensitive to capture
physiological and pathological variations in the human brain, namely changes in
the grey matter structure of the cerebellum, changes in the functional
connectivity of the cerebellum, and changes in the cerebral circuits supporting
gait and balance. The results of this project will be important for structuring
future training interventions.

Explorative study.

Before the training:
Fysical examination
Kinematic analysis of gait and balance
Baseline MRI scan session including: structural MRI, DWI, funtional
restingstate MRI en functional task MRI.

Training:
5 weeks of C-mill training, twice a week, one hour per session

After training:
Kinematic analysis of gait and balance
MRI session including: structural MRI, DWI, funtional restingstate MRI en
functional task MRI

To control if the cerebral changes are due to the training, rather than to
spontaneous fluctuations, 5 patients and 5 healthy subjects will undergo an
extra MRI measurement 5 weeks before the start of the C-mill training. This MRI
protocol is similar to those above.

There are no clear risks for the participants.

The burden consists of undergoing MRI scans, kinematic analysis of gait and
balance, and 10 training sessions.
This will take about 15 hours in total (excluding time for travel)