Abstract
In neurology, as in all branches of medicine, symptoms of disease and the resulting burden of illness and disability are not simply the consequence of the injury, inflammation or dysfunction of a given organ; they also reflect the consequences of the nervous system's attempt to adapt to the insult. This plastic response includes compensatory changes that prove adaptive for the individual, as well as changes that contribute to functional disability and are, therefore, maladaptive. In this context, brain stimulation techniques tailored to modulate individual plastic changes associated with neurological diseases might enhance clinical benefits and minimize adverse effects. In this Review, we discuss the use of two noninvasive brain stimulation techniques—repetitive transcranial magnetic stimulation and transcranial direct current stimulation—to modulate activity in the targeted cortex or in a dysfunctional network, to restore an adaptive equilibrium in a disrupted network for best behavioral outcome, and to suppress plastic changes for functional advantage. We review randomized controlled studies, in focal epilepsy, Parkinson's disease, recovery from stroke, and chronic pain, to illustrate these principles, and we present evidence for the clinical effects of these two techniques.
Key points
The clinical consequences of brain insults include compensatory plastic changes that can be either adaptive or maladaptive
An ideal therapy should be tailored to the individual, promote compensatory plastic changes, inhibit maladaptive plastic changes, be associated with minimal or no adverse effects, be highly effective, and be financially and practically feasible
An advantage of brain stimulation is that it can be focal and targeted to the underlying pathophysiology of the patient
Two techniques of noninvasive brain stimulation—repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS)—are powerful tools for brain modulation
A growing number of proof-of-principle and pilot studies have revealed that rTMS and tDCS are associated with mild adverse effects and can induce clinical benefits; however, the evidence for efficacy is currently insufficient
Initial studies have shown that noninvasive brain stimulation can be used to modulate activity in the targeted cortex (focal epilepsy); modulate activity in a dysfunctional corticosubcortical network (Parkinson's disease); restore adaptive equilibrium in a disrupted network (stroke); or suppress plastic changes for functional advantage (pain)
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Acknowledgements
This work was partially supported by grants from the NIH (K24 RR018875, RO1-DC05672, RO1-NS 47754, RO1-NS 20068, R01-EB 005047, RO1-NS47754, RO3-DK071851).
Author information
Affiliations
F Fregni is an Instructor in Neurology at Harvard Medical School and the Beth Israel Deaconess Medical Center, and Director of the Clinical Trials Network at the Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Boston, MA, USA.
- Felipe Fregni
A Pascual-Leone is the Director of the Berenson-Allen Center for Noninvasive Brain Stimulation and Professor of Neurology at Harvard Medical School and the Beth Israel Deaconess Medical Center; he is also the Associate Director of the Harvard-Thorndike General Clinical Research Center, Boston, MA, USA.
- Alvaro Pascual-Leone
Authors
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Competing interests
A Pascual-Leone holds the patent for the TMS–EEG combination (US Patent 6571123), and has received research grants from Northstar Neuroscience for cortical stimulation work. F Fregni declared he has no competing interests.
Corresponding author
Correspondence to Alvaro Pascual-Leone.
Supplementary information
Word documents
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Supplementary Table 1
Noninvasive brain stimulation and chronic pain
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Supplementary Table 2
Noninvasive brain stimulation and stroke
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Supplementary Table 3
Noninvasive brain stimulation and Parkinson's disease
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Supplementary Table 4
Noninvasive brain stimulation and epilepsy
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