Transcranial Direct Current Stimulation (tDCS) in Chronic Stroke Recovery

We have tested the effectiveness of each stimulation condition: 1) anodal over the lesional
motor cortex 2) anodal PMD (positive electrode at the dorsal premotor cortex (PMD) of the
lesional hemisphere (first phase) or dual motor cortex stimulation (second phase), 3)
cathodal over the contralesional motor cortex, and 4) sham in a double blind crossover
design in chronic cortical and subcortical strokes.

Persons in the chronic stage of recovery from stroke (>3 months) will receive each type of
tDCS stimulation for 20 minutes concurrent with physical therapy treatments (90 minutes )
utilizing the Armeo ®, a gravity neutral arm exercise support system for the most involved
upper extremity which provides for task practice in a virtual reality environment, followed
by a therapist supervised targeted hand exercise. The experimental protocol will not alter
standard of care, will be performed after standard rehabilitation is completed. The
experimental therapy is not part of standard care and will not be charged or reimbursed by
the patients' insurance. Participation will be free of charge for subjects.

We were planning to perform the study in two phases. In the first exploratory phase, we will
conduct a short pilot study with 15 subjects to optimize and if possible simplify the
treatment parameters for the second longer phase of the experiment. In this first phase we
will perform one of the four different tDCS stimulation conditions concurrently with the
physical therapy protocol on each therapy day, so that all subjects will receive all
stimulation types in a randomized counterbalanced order. There will be a 1 day rest period
in between sessions, making 9 days (10 days if initial evaluation is done on the day before
the 1st treatment) the total commitment time for the first phase of study.

The outcome measures were collected before and after each session. The outcome measures
collected after the 1 day rest provide the baseline for the next session will be also used
as to validate the stability of the treatment effect. Subjects participating in the first
part of the study will be offered the option to participate in the second longer phase of
the study. (please see table under study procedures)

In the second phase of the experiment we will perform only the promising stimulation
paradigms plus sham from the first part of the experiment in a random, counterbalanced order
on up to 30 chronic stroke subjects. If in the initial phase there are no differences found
between stimulation types in the cortical vs subcortical patient groups then all 3
stimulation paradigms will be performed in the second phase.

Based on our preliminary data, we will perform the following paradigms in the second phase:
1) sham 2) dual stimulation 3) optimized tDCS in a randomized counterbalanced order. The
optimized tDCS will be determined during a test session prior to the first treatment where
the tDCS montage producing the best behavioral response will be used during therapy.
Subjects will perform this under IRB approved study # STU 102013-085.

The patient time commitment in the second phase is 18 weeks, where subjects will have 3 x 1
weeks long treatment (5 weekdays) sessions with 5 week inter-treatment "rest period". The
blinded tester will perform a final outcome evaluation 5 weeks after the end of the last
session. (please see table under study procedures)

Total number of potential enrolled subjects for both phases will be approximately 45 [Phase
1 (15) + Phase 2 (30)].

The stepwise design will enable us to optimize study time commitment and expenses for both
patients and researchers while maximizing clinical/scientific gain.

Inclusion Criteria:

- single symptomatic stroke more than 3 months ago with hand/arm weakness

- able to perform required tests and provide consent

- Age 18-80

- Modified Ashworth scale <3

- range of motion functional at shoulder elbow wrist and hand

Exclusion Criteria:

- more than one symptomatic stroke in middle cerebral artery territory or bilateral
involvement

- severe medical or psychiatric conditions, drug abuse, seizure disorder

- pregnancy/breast feeding

- subarachnoid hemorrhage, lobar hemorrhage

- patients who can not have tDCS (prior head surgery, pacemakers, metallic implants in
the head etc)

- patients taking antiadrenergic medications