Long- Term Transcranial Direct Current Stimulation in Parkinson's Disease
Long- Term Transcranial Direct Current Stimulation in Parkinson's Disease
The goal of the proposed research is to determine the influence of transcranial direct
 current stimulation (tDCS) on long-term motor learning, transfer of motor learning, and
 cortical function in Parkinson's disease (PD). The project comprises a 2 week training study
 that will involve tDCS applied during two practice motor tasks with behavioral, clinical, and
 physiological evaluations at baseline as well as 1, 14 and 28 days following the 2 week
 training and stimulation period. The findings of the proposed studies should have significant
 clinical significance and applications to comprehensive intervention therapy development in
 the treatment of PD.
Parkinson's disease (PD) is the second most common neurodegenerative disorder and affects
 approximately 1 million people in the United States with total annual costs approaching 11
 billion dollars. Current medical and surgical treatment approaches for PD are either only
 mildly effective, expensive, or associated with a variety of side effects. Therefore, the
 development of practical and effective therapeutic adjuncts to current treatment approaches
 would have significant benefits.

 Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique
 that can modulate cortical excitability and improve motor function in healthy subjects, older
 adults, and in stroke. However, there are several crucial issues that currently prevents the
 determination of the viability of tDCS as an adjunct intervention in PD. For example, the
 magnitude to which tDCS may be able to improve long-term motor learning beyond what can be
 achieved by practice alone in PD is unknown. It is also unclear if short-term improvements in
 motor function induced by tDCS and measured in the OFF state in PD can be attained over the
 long-term in the ON state, which is necessary for real world application. In addition, it is
 uncertain if the effects of tDCS generalize to non-practiced tasks and to the ipsilateral,
 non-tDCS stimulated hand. Finally, the physiological mechanisms underlying any of these
 issues have not been identified because no long-term motor learning tDCS studies in PD to
 date have concurrently quantified behavioral, clinical, and physiological measures.

 The project will be a single-center, double-blind, randomized, sham-controlled, experimental
 design. PD patients will practice 2 motor tasks (practice tasks) with their right (primarily
 affected) hand in 9 practice sessions over a 2 week period in association with either tDCS or
 SHAM stimulation of the left (contralateral) motor cortex. In addition, 4 testing sessions
 will be performed and will include a Baseline test, an end of training test (EOT), a follow
 up test 2 weeks after the end of training (EOT+14), and a follow up test 4 weeks after the
 end of training (EOT+28). The primary outcome variables will be the force error in the first
 practice task (precision grip task; PGT) and the stroke amplitude, stroke variability, and
 writing speed in the second practice task (handwriting task; HWT). The secondary outcome
 variables the Unified Parkinson's Disease Rating Scale (UPDRS) Part 3, the Purdue Pegboard
 Test (PT), and the Jebsen Taylor Hand Function Test (JTT).
Inclusion Criteria:

 1. Able to provide informed consent.

 2. A clinical diagnosis of idiopathic PD.

 3. A stable and optimal medical regimen of anti-parkinsonian drug therapy for the
 duration of the study.

 4. Modified Hoehn and Yahr stage between 1.0 and 3.0 in the OFF state.

 5. Right-hand dominant and primarily right-side affected to prevent confounds due to
 handedness and affected side.

 Exclusion Criteria:

 1. An uncontrolled medical condition (i.e. hypertension, diabetes, etc).

 2. Evidence of secondary or atypical parkinsonism as suggested by:

 1. History of CVA's, exposure to toxins, neuroleptics or encephalitis.

 2. Neurologic signs of upper motor neuron or cerebellar involvement, supranuclear
 gaze palsy or significant orthostatic hypertension.

 3. Metal in the skull or the eye, such as a cardiac pacemaker, brain stimulator,
 shrapnel, surgical metal, clips in the brain, cochlear implants, and metal fragments
 in the eye, as these may make TMS and tDCS unsafe.

 4. An uncertainty about the presence of metal objects in a subject's body exists.

 5. Hearing loss, have had a brain tumor, a stroke, head trauma, epilepsy or a history of
 seizures, have another neurological disorder other than a movement disorder, or have a
 head injury where they passed out for more than a few seconds.

 6. Pregnant or thought to be pregnant.

 7. Irrepressible dyskinesia or tremor to prevent the confound of excessive EMG during TMS
 testing at rest.

 8. Any other neurological disorders.

 9. Meeting of any of the TMS exclusion criteria given in international guidelines.