Fall 2011 - Institute of Medical Science - University of Toronto

SPOTLIGHT
Transcranial magnetic stimulation
An investigational tool and potential therapeutic option in movement disorders
By Nina Bahl
Arguably the most important
organ in the body, the brain is also
the least understood; comprised of
a staggering one hundred billion neurons,
the complexity of the connectivity between
these cells seems nearly incomprehensible.
Accordingly, our understanding of human
neurophysiology has benefited tremendously
from the advent of sophisticated investigational
tools, including transcranial magnetic
stimulation (TMS) – a non-invasive method
of stimulating the brain. For Dr. Robert
Chen, a senior scientist and movement disorders
specialist at Toronto Western Hospital,
the utility of TMS has proven invaluable
to his investigations of motor cortex functionality
and of the pathophysiology and associated
treatments of movement disorders.
Stimulation is produced by generating a
brief, high-current pulse in a magnetic coil
that is placed on the scalp of the subject. This
transient current induces a large and changing
magnetic field, which subsequently produces
an electric current in the underlying
brain 1,2 .
For studies involving the motor cortex, as in
Chen’s lab, TMS pulses are typically administered
to the region of the brain that controls
a specific hand muscle. Here, stimulation
produces a focal twitch in the target muscle,
which is measured with surface electrodes
placed on the hand, and visualized on an
electromyogram. This muscle response to
TMS is termed the motor-evoked potential,
the amplitude of which is thought to reflect
motor cortex excitability 2,3 . Thus, human
cortical excitability can be assessed using a
number of specific TMS measures that are
based on this fundamental principle.
While using TMS techniques during a research
fellowship at the National Institutes of
Health, Chen quickly appreciated the versatility
and uniqueness of TMS as a neurophysiological
probe. “It really is a fascinating way
to study the brain,” he affirms. “By stimulating
neural regions without any sort of invasive
method, you can measure a subject’s re-
sponse in a number of ways and reveal fairly
specific information about their [cortical]
physiology. There aren’t many other methods
that can offer such a direct investigation in
humans, so [TMS] is a very powerful tool.”
Upon establishing his laboratory at the Toronto
Western Research Institute in 1998,
Chen predominantly adopted TMS techniques
for use in his lab, which currently
focuses its studies on patient populations to
elucidate pathological mechanisms in a number
of movement disorders. One of the most
commonly studied pathologies in the lab is
Parkinson’s disease (PD), a neurodegenerative
disorder that causes a variety of debilitating
motor symptoms, including bradykinesia,
rigidity, and tremor. “Our [studies]
have revealed several cortical changes in PD
patients – as one example, we see a reduction
in one form of motor cortical inhibition,” he
notes. By understanding details such as these,
the hope is to be able to piece together how
neuronal degeneration in a disorder like PD
translates into its overt symptoms, which is
currently not well understood.
Chen’s team has also used TMS techniques
to explore deep-brain stimulation (DBS),
which is one of the most remarkable neurosurgical
advances for PD and a handful
of other movement disorders. “When DBS
emerged as a new treatment around 2000,
our lab began investigating it soon after. One
of the challenges is that we still don’t know
how it works.” Chen aims to reveal potential
mechanisms of action of DBS, and specifically,
explore how deep-brain nuclei (where
DBS implants are located) may be modulating
the motor cortex to produce clinical improvements
in patients with disordered motor
control.
Other major TMS investigations in his lab include
studies of normal human motor physiology,
including the examination of how
different neuronal circuits interact with one
another in the motor cortex. As well, his lab
uses genetic techniques as an adjunct to examine
the effects of selected single nucleotide
polymorphisms on brain functionality and
its ability to undergo plasticity and learning.
Undeniably, for Dr. Chen, TMS has proven
Photo by Paulina Rzeczkowska
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