Transcranial magnetic stimulation for PSP and CBD

There seems to be increased interest around the world in TMS – transcranial magnetic stimulation.

CurePSP, the new name for the Society for PSP, recently announced that it is funding a small study of TMS in 10 PSPers and ten CBDers at UCLA. Here’s info on the study being funded — first a non-technical summary and then a technical abstract:

http://www.psp.org/doc_library/12283993 … ebsite.pdf –> see pages 13 and 14

CurePSP Magazine
Fall 2008

Cure PSP Awards Two New Grants in Spring 2008

Noninvasive Cortical Stimulation for Motor and Non-motor Features of PSP and CBD
Allan D. Wu, MD — University of California, Los Angeles

Non-Technical Abstract
Drug therapy of atypical parkinsonism is generally considered either ineffective or minimal. Therefore, there is an urgent need to find alternative therapies to treat atypical parkinsonian disorders. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive tool that modulates cortical excitability with minimal discomfort and holds therapeutic promise in treating neurological and psychiatric disorders.

The basal ganglia-thalamocortical circuits that are affected in PSP and CBD are likely structurally and functionally segregated. The ‘motor’ circuit is implicated in classic motor symptoms such as dystonia and parkinsonian slowness and stiffness; a ‘prefrontal’ circuit is implicated in working memory and mood regulation and may be linked with non-motor symptoms such as depression and apathy. In this proposal, we characterize motor and prefrontal network dysfunction in PSP and CBD patients, and propose that high-frequency rTMS directed over separate motor and prefrontal cortical targets of each network may show specific and selective beneficial effective on motor vs. cognitive function in PSP/CBD patients. Quantitative motor outcome measures include the Purdue pegboard, timed walking and timed tapping tasks. Quantitative cognitive outcomes measures comprise a novel 2-back working memory (WM) task and its emotional modulation as assessed with pictures of faces showing differential emotions.

If successful, this pilot study will provide proof of principle data to suggest potential benefits for rTMS in PSP/CBD patients, and provide sufficient data and experience to support future PSP/CBD studies that include the use of rTMS to investigate the pathophysiology of motor and non-motor features of PSP and CBD patients.

Structured Technical Abstract
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 PSP/CBD are associated with a dysfunctional motor network; deficits in WM and its emotional regulation in PSP/CBD are associated with a dysfunctional prefrontal network. We hypothesize that high-frequency rTMS over cortical targets will selectively and specifically improve tasks and symptoms relevant to that target.

Aims: To contrast motor, WM, and emotional regulation between PSP/CBD patients and age-matched controls. To determine selective and specific beneficial rTMS effects over motor (M1) and dorsolateral prefrontal (DLPFC) cortex on motor, WM and its emotional regulation in PSP/CBD.

Design: Ten individuals with PSP, 10 with CBD, and 10 age-matched controls will participate in a within-subject cross-sectional design. Motor outcome measures include the Purdue pegboard, a walking test, and a tapping test. Cognitive outcome measures comprise a 2-back task and its emotional modulation assessed with pictures of affective faces. Subjects will receive at least two 5 Hz rTMS visits that will be randomized to two site conditions (left DLPFC vs. M1) across subjects with two within-session task conditions (motor vs. cognitive).

Relevance: If successful, we will demonstrate a double-dissociation and causal functional significance between rTMS modulation of M1 in motor tasks and DLPFC in WM and its emotional modulation in PSP/CBD vs. controls. Sufficient data and experience for future PSP/CBD intervention studies will help identify candidate TMS parameters that are optimal for given symptoms.

Abbreviations: progressive supranuclear palsy (PSP), corticobasal (ganglionic) degeneration (CBD), repetitive transcranial magnetic stimulation (rTMS), primary motor area (M1), dorsolateral prefrontal cortex (DLPFC), working memory (WM).