Contribution of the Cerebellum In Sensory-motor Adaptation Via Gamma Oscillations: the Case of Dystonia (GAMMA)

• ClinicalTrials.gov Identifier: NCT02073630
• Recruitment Status: Completed
• First Posted: February 27, 2014
• Last Update Posted: November 6, 2017
• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Information provided by (Responsible Party): Institut National de la Santé Et de la Recherche Médicale, France

Study Description

Brief Summary:

Dystonia, a disabling disease with uncontrolled movement disorders was considered to be a manifestation of basal ganglia dysfunction, yet there is accumulating evidence from animal and human experiments that the cerebellum plays a prominent role in the pathophysiology of dystonia. Our recent results suggest a deficient cerebellar sensory encoding in dystonia, resulting in a decoupling of the motor component from the afferent information flow resulting from changes in the environment. An overall loss of gabaergic-mediated inhibition is at the forefront in dynamic changes in neural circuitry described in dystonia. In the mature brain gabaergic control the generation of temporal synchronies and oscillations in the glutamatergic neurons. Taken these all together with the results of a pilot experiment, the investigators hypothesize that deficient synchronies in the fast gamma range are one of the key mechanisms leading to abnormal communication inside the cerebello-cortical network in dystonia. The investigators aim first to demonstrate it by means of MEG (Magneto encepholography) recordings allowing to reconstruct the spatio-temporal dynamics of gamma oscillations in the nodes of the cerebello-cortical network. The investigators then aim to re-establish (if lost) or boost (if decreased) the defective synchronies by applying to the cerebellum at high gamma frequency a non invasive transcranial alternative current stimulation.

Condition or disease	Intervention/treatment	Phase
Primary Dystonia	Other: active cerebellar stimulation; Other: sham cerebellar stimulation	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 63 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Basic Science
• Official Title: Contribution du Cervelet Dans l'Adaptation Sensori-motrice Via Les Oscillations Gamma : le Cas de la Dystonie
• Study Start Date: February 2014
• Actual Primary Completion Date: February 2016
• Actual Study Completion Date: August 2016

Arms and Interventions

Arm	Intervention/treatment
Healthy subjects; healthy subjects will receive either sham or active cerebellar stimulation	Other: active cerebellar stimulation; Other: sham cerebellar stimulation
Dystonia; dystonic patients will receive either sham or active cerebellar stimulation	Other: active cerebellar stimulation; Other: sham cerebellar stimulation

Outcome Measures

Primary Outcome Measures :

1. change in gamma oscillations power in the cerebellum during a sensorimotor adaptation task [ Time Frame: measures will be done at each of 3 visits: visit1, visit2 at expected average 7 days after visit1 and visit3 at expected average 14 days after visit1 ]

   MEG recording will be performed using a whole-head 306-channels MEG system (Elekta Neuromag® TriuxTM System) comprising 204 planar gradiometers and 102 magnetometers regularly distributed at 102 locations over the scalp. MEG data will be coregistered with the structural MRI of each subject using BrainStorm (http://neuroimage.usc.edu/brainstorm).

   The localization of the source will be constrained with the individual anatomy obtained with MRI.

Secondary Outcome Measures :

1. synchrony in the gamma band between the cerebellum and the sensorimotor cortex [ Time Frame: measures will be done at each of 3 visits: visit1, visit2 at expected average 7 days after visit1 and visit3 at expected average 14 days after visit1 ]
   We will also conduct a functional connectivity analysis to assess the neuronal interactions between the cerebellum and the thalamus, the thalamus and the motor cortex by quantifying correlations between power envelopes. We will compute Pearson's linear correlation between the power envelopes from two different locations (between couples of magnetometers and couples of nodes at the source level).

Other Outcome Measures:

1. behavioral performances at a sensorimotor adaptation task [ Time Frame: measures will be done at each of 3 visits: visit1, visit2 at expected average 7 days after visit1 and visit3 at expected average 14 days after visit1 ]
   Subjects will have to reach six different targets positioned on a half-circle and appearing in a predictable order on a computer screen by moving a amagnetic joystick with their right hand. During the direct condition, there will be a direct coupling between the joystick and the cursor position. During the indirect conditions, 4 different rotations between the joystick and the cursor positions will be introduced. During one session the shifts will be 10°, 30°, -20°, -40° and in the other session -10°, -30°, 20°, 40° in order to reduce possible skill transfer from the baseline session to the stimulation session. Indirect and direct trials will be randomized to avoid habituation and learning within a session. There will be 2 blocks of 160 trials. In each block, there will be 20 trials for each rotation and 80 trials of the direct condition

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• primary upper limb dystonia
• normal physical and neurological examination except for dystonia
• no treatment with botulinum toxin during the three months preceding the study

Exclusion Criteria:

• Writing tremor
• current neurological or psychiatric illness other than dystonia
• uncontrollable medical problems not related to dystonia
• pregnancy, breast feeding women and women who are of childbearing age and not practicing adequate birth control

Contacts and Locations

Locations

France

ICM GH Pitié Salpetrière

Paris, France, 75651

Sponsors and Collaborators

Institut National de la Santé Et de la Recherche Médicale, France

Investigators

• Principal Investigator: sabine meunier, MD, PhD; Institut National de la Santé Et de la Recherche Médicale, France

More Information

• Responsible Party: Institut National de la Santé Et de la Recherche Médicale, France
• ClinicalTrials.gov Identifier: NCT02073630
• Other Study ID Numbers: C13-45
• First Posted: February 27, 2014
• Last Update Posted: November 6, 2017
• Last Verified: August 2016

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Institut National de la Santé Et de la Recherche Médicale, France:

magnetoencephalography; non invasive brain stimulation; cerebellum; gamma rhythms

Additional relevant MeSH terms:

Dystonia; Dystonic Disorders; Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Movement Disorders; Central Nervous System Diseases