Repetitive Transcranial Magnetic Stimulation (TMS) for Progressive Supranuclear Palsy and Corticobasal Degeneration

Background: Drug therapy of atypical parkinsonism is generally ineffective or minimal, and
novel therapy approaches for atypical parkinsonian disorders are needed. Repetitive
transcranial magnetic stimulation (rTMS) is a noninvasive tool that modulates cortical
excitability and holds promise in treating neurological/psychiatric disorders. The 'motor'
basal ganglia-cortical circuit is implicated in parkinsonian akinesia and hypokinesia; a
'prefrontal' circuit is implicated in working memory (WM) and mood regulation, possibly
linked to depression and apathy.

Hypothesis: Motor deficits in Progressive Supranuclear Palsy (PSP) and Corticobasal
Ganglionic Degeneration (CBGD) are associated with a dysfunctional motor network; emotional
deficits in PSP/CBGD are associated with a dysfunctional prefrontal network. We hypothesize
that high-frequency and low-frequency rTMS over cortical targets will selectively and
specifically improve tasks and symptoms relevant to that target in PSP and CBGD patients,
respectively.

Aims: To contrast cortical excitability characteristics and motor and emotional function
between PSP and CBGD patients. To determine selective and specific beneficial rTMS effects
over primary motor (M1) and dorsolateral prefrontal (DLPFC) cortex on cortical excitability
characteristics and motor and emotional function in PSP and CBGD patients.

Design: Ten individuals with PSP and ten with CBGD will participate in a within-subject
cross-sectional design. Motor outcome measures include a timed finger tapping task at
comfortable and maximal speed. Quantitative cognitive outcome measures comprise a visual
analogue scale of mood states (VAS). After a first baseline visit, PSP patients will receive
high-frequency 5 Hz rTMS in two separate visits to two site conditions (left DLPFC vs. the
more affected side of M1) across subjects with two within-session task conditions (motor vs.
cognitive). They will also receive sham stimulation in a separate visit. These three
stimulation visits will be randomized. CBGD patients will receive the same treatment with
the only difference that they will receive low-frequency 1 Hz rTMS instead.

Relevance: If successful, we will demonstrate a double-dissociation and causal functional
significance between rTMS modulation of M1 in motor tasks and DLPFC in emotional function in
PSP Vs. CBGD. Exploratory aims will be conducted. Sufficient data and experience for future
PSP/CBGD intervention studies will help identify candidate TMS parameters that are optimal
for given symptoms.

Inclusion Criteria:

If you are an adult with PSP or CBGD:

1. Must be in good physical health.

If you are neurologically healthy volunteers:

1. Must be older than 35 years

Exclusion Criteria:

1. Must have no implanted metal. Dental fillings are acceptable.

2. Must have no personal seizure or 1st degree relative with history of seizures

3. Must not take any medication that lowers seizure threshold.