Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Apathy in Parkinson's Disease (ReStore)

University of Florida

Status: Completed

Conditions: Parkinson's Disease

Treatments: Device: Sham Repetitive Transcranial Magnetic Stimulation; Device: High-Frequency Repetitive Transcranial Magnetic Stimulation

Study type: Interventional

Funder types: Other

Identifiers

NCT00955032

0004762006

Details and patient eligibility

About

The purpose of this research study is to attempt to treat apathy in Parkinson's disease (PD) using high-frequency repetitive transcranial magnetic stimulation (rTMS) of the brain and to investigate the patterns of brain activation that may be involved in apathy. It is hypothesized that high-frequency rTMS of the left mid-dorsolateral frontal cortex will improve apathy in PD.

Full description

Apathy is a syndrome characterized by a primary lack of motivation and it manifests in three domains: behavioral (lack of effort and productivity, dependence on others for structuring daily activities), cognitive (loss of interest in new experiences, lack of concern for one's problems) and affective (flattened affect and lack of response to positive or negative events). Apathy has been consistently attributed to functional disturbance of neural systems involving mesial frontal and the anterior cingulate cortex (ACC), an area with reciprocal connections with limbic, frontal cortices and the basal ganglia.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive tool used to manipulate activity in specific brain neural circuits through the skull and, in turn, induce short-term (milliseconds) and long-term (minutes to hours) changes in behavior. The duration of effect depends on the stimulation mode. Several studies have now demonstrated that rTMS may facilitate or modulate behavior beyond the actual stimulation. rTMS of the mid-dorsolateral frontal cortex (MDLFC) has been used to treat depression presumably because of its modulatory effect on the fronto-cingulate system (MDLFC and the ACC circuitry). Studies have shown that rTMS of the left MDLFC modulates the blood flow response in the ACC. We therefore hypothesize that high-frequency rTMS of the left MDLFC will also improve apathy in PD.

Enrollment: 24 patients

Sex: All

Ages: 30+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. diagnosis of "probable" PD, defined by the presence of at least 2 out of 3 cardinal motor features of PD (resting tremor, rigidity, and bradykinesia, plus a sustained and significant response to dopaminergic treatment);
2. age 30 or over; and
3. on stable medications for at least 30 days.

Exclusion criteria

1. features suggestive of other causes of parkinsonism/ parkinson-plus syndromes;
2. history of deep brain stimulation or ablation surgery, significant headaches, epilepsy or seizure disorder, mass brain lesions, or major head trauma leading to loss of consciousness of any length;
3. family (1st degree relatives) history of epilepsy;
4. evidence for dementia;
5. presence of contraindications for functional magnetic resonance imaging (fMRI);
6. history of schizophrenia, schizoaffective disorder, other psychosis, rapid-cycling bipolar illness, alcohol/drug abuse within the past year;
7. need for rapid clinical response due to conditions such as initiation, psychosis, or suicidality;
8. unstable medical condition such as diabetes, cardiac disease, hypertension;
9. pregnancy; and
10. colorblindness.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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24 participants in 2 patient groups

High-Frequency Repetitive Transcranial Magentic Stimulation

Experimental group

Description:

High-Frequency repetitive transcranial magnetic stimulation patients randomized to this treatment will receive left prefrontal rTMS, each treatment will consist of 2000 stimuli (50 - 8-second trains of 40 stimuli at 5 Hz). We will administer rTMS trains every 30 seconds for 25 minutes. Stimulus intensity for the first and second trains will be 80 and 90% of Motor Evoked Potential (MEP) threshold, respectively.

Treatment:

Device: High-Frequency Repetitive Transcranial Magnetic Stimulation

Sham Repetitive Transcranial Magentic Stimulation

Sham Comparator group

Description:

Sham repetitive transcranial magnetic stimulation patients randomized to receive the sham rTMS will undergo the same procedure for identifying stimulus location used in patients receiving real rTMS. Simulated rTMS will be administered using Magstim Placebo 70 mm figure-of-8 shaped coils which produce discharge noise and vibration similar to a real 70 mm coil without stimulating the cerebral cortex. However, in addition to obvious coil discharge noise, rTMS also causes electrical stimulation of the scalp. We will simulate this experience by attaching surface electrodes underneath the sham coil and in contact with the scalp.

Treatment:

Device: Sham Repetitive Transcranial Magnetic Stimulation