Clinical Trial Details
— Status: Active, not recruiting
Administrative data
NCT number |
NCT05351255 |
Other study ID # |
AEHN-IRB-2022-881 |
Secondary ID |
|
Status |
Active, not recruiting |
Phase |
N/A
|
First received |
|
Last updated |
|
Start date |
July 1, 2022 |
Est. completion date |
August 30, 2025 |
Study information
Verified date |
August 2023 |
Source |
Albert Einstein Healthcare Network |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
This study will determine (1) whether baseline inhibitory activity in the primary motor
cortex can predict motor learning ability in individuals with cerebellar degeneration, and
(2) whether modulating primary motor cortex activity with non-invasive brain stimulation
alters motor learning ability in this population.
Description:
Cerebellar damage causes the disabling movement disorder ataxia, which is characterized by
impaired movement coordination affecting all body movements. In the arms, ataxia causes
reaching movements with irregular, oscillating, and prolonged trajectory paths. People with
cerebellar ataxia (PWCA) are also impaired in an important form of motor learning, called
adaptation, which normally keeps movement well calibrated. In prior research, the principal
investigator showed that PWCA can learn to correct their reaching movements if they instead
employ reinforcement learning (RL). Although many PWCA learned optimally in RL conditions,
this prior work found variability across individuals: some learned more than others. While
adaptation critically relies on cerebellar integrity, RL depends more heavily on dopaminergic
circuitry in the midbrain and excitatory plasticity in M1. Cerebellar damage has been shown
to increase intracortical inhibition in M1, which may hamper the plasticity needed for RL.
The repetitive TMS protocols of continuous theta burst stimulation (cTBS) and intermittent
theta burst stimulation (iTBS) have further been shown to modulate intracortical inhibition:
cTBS decreases it, while iTBS increases it. Here, the investigators will systematically test
whether increased intracortical inhibition in M1 predicts RL capacity (Aim 1) and whether
modulating inhibition in M1 can alter RL capacity in PWCA (Aim 2). 12 PWCA from a
degenerative condition will complete 4 experimental sessions over a 6-month period. In
session 1, TMS will be used to assess baseline recruitment curves for corticomotor
excitability and short-interval intracortical inhibition, and the cortical silent period.
PWCA will then complete a standardized clinical rating of their ataxia severity and an
established behavioral task that requires learning a reaching skill using the RL paradigm. In
sessions 2-4, PWCA will complete 3 additional sessions of the RL task. In each session, PWCA
will receive cTBS, iTBS, or sham stimulation to modulate intracortical inhibition in M1 prior
to performing the RL task. For Aim 1, the investigators will use multi-level regression to
quantify relationships between TMS measures of M1 state and the magnitude and speed of
learning in the RL task. For Aim 2, the investigators will use multi-level modeling to
quantify differences in the magnitude and speed of learning across stimulation conditions.
The investigators hypothesize that increased baseline inhibition in M1 will show a positive
association with a lower magnitude and speed of learning in the RL task (Aim 1), and cTBS
will improve the magnitude of learning, the speed of learning, or both, in the RL task
relative to iTBS or sham stimulation (Aim 2).