Assessment of tDCS-Induced Neuronal Responses in Multiple Sclerosis (MS) With Advanced MRI

Study Overview
=================
Brief Summary
-----------------
The objective of this trial is to measure the changes in neural activities during tDCS session using Magnetic Resonance Imaging (MRI). Participants (N=60) (20 Healthy Controls and 40 participants with neurological disorders, ie. multiple sclerosis) will be recruited to complete self-report measures and a brief cognitive assessment and then undergo an hour long stand-alone MRI scan while simultaneously undergoing tDCS stimulation. Methodology for this study is the administration of 15-minutes of of active tDCS during MRI acquisition compared to time without active tDCS.

Official Title
-----------------
Assessment of tDCS-Induced Neuronal Responses in Multiple Sclerosis (MS) With Advanced MRI

Conditions
-----------------
Multiple Sclerosis

Intervention / Treatment
-----------------
* Other: Active tDCS
* Other: Sham (placebo) stimulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Standardized SDMT Z-scores ≥3 standard deviations below mean Able to understand all study instructions and supply written consent Exclusion Criteria: Extreme claustrophobia History of mental retardation, pervasive developmental disorder or other neurological condition associated with cognitive impairment Primary psychiatric disorder that would influence ability to participate History of seizures or seizure disorder History of head trauma in the past year (e.g., head injury, brain surgery) or medical device implanted in the head (such as Deep Brain Stimulator) or in the neck (such as a Vagus Nerve Stimulator) Any skin disorder/sensitive skin (e.g., eczema, severe rashes), blisters, open wounds, burn including sunburns, cuts or irritation, or other skin defects which compromise the integrity of the skin at or near stimulation locations (where electrodes are placed) Treatment for a communicable skin disorder currently or over the past 12 months History of uncontrolled or labile hypertension. Have any irremovable piercings, implantations or metallic-based tattoos History of clinically significant abnormalities on electrocardiogram (EKG) Pregnant or breastfeeding Current substance abuse disorder

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Participants (N=60) (20 Healthy Controls and 40 participants with neurological disorders, ie. multiple sclerosis) will be recruited to complete self-report measures and a brief cognitive assessment and then undergo an hour long stand-alone MRI scan while simultaneously undergoing tDCS stimulation.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Healthy Controls<br>20 Healthy Controls | Other: Active tDCS<br>* The simultaneous tDCS will be performed at up to 2 mA dose intensity to determine CMRO2 changes from when the tDCS is on when the tDCS is off. The stimulation (left anodal at DLPFC regions) consists of 15-min up to 4 mA tDCS using 5x5 cm electrode sponge with  30s ramp-up and ramp-down periods.<br>Other: Sham (placebo) stimulation<br>* MRI-compatible tDCS off (immediately before and after tDCS)<br>|
| Experimental: MS Patients<br>40 individuals diagnosed with MS recruited from the MS Center/ Neurology Department at NYULMC | Other: Active tDCS<br>* The simultaneous tDCS will be performed at up to 2 mA dose intensity to determine CMRO2 changes from when the tDCS is on when the tDCS is off. The stimulation (left anodal at DLPFC regions) consists of 15-min up to 4 mA tDCS using 5x5 cm electrode sponge with  30s ramp-up and ramp-down periods.<br>Other: Sham (placebo) stimulation<br>* MRI-compatible tDCS off (immediately before and after tDCS)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cerebral metabolic rate of oxygen (CMRO2): | The vastly energetic brain has high cerebral O2 consumption, which is critical for neuronal functions and is proportional to neuronal and synaptic activity changes. | 15 Minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuronal Reactivity (NR) | NR represents tDCS-induced global neural reactivity measured by CMRO2 levels in cells available to respond to neural stimuli. | 15 Minutes | 
| Functional connectivity (FC) | Functional networks of DLPFC will be extracted from pre-processed RS-fMRI data prepared within C-PAC toolbox. | 15 Minutes | 
| Fractional Amplitude of Low Frequency Fluctuations (fALFF) | fALFF [36] is a RS-fMRI measure that quantifies the baseline neural activity by low frequency oscillations at rest. | 15 Minutes | 
| Voxel-mirrored homotopic connectivity (VMHC) | VMHC characterizes synchrony in patterns of spontaneous activity between symmetric homotopic (geometrically corresponding) cortical regions (e.g., DLPFC) in each hemisphere. | 15 Minutes | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Anodal transcranial stimulation (tDCS)