5
Using Non-Invasive Neuromodulation for Diagnosis and Research
Highlights
- The assessment of brain responses to non-invasive neurostimulation may be useful in the diagnosis of upper motor neuron involvement in neuromuscular disorders, spinal cord lesions, multiple sclerosis, PD, and Alzheimer’s disease. (Chen)
- These techniques may also be useful to assess disease progression, predict response to therapy, presurgically map eloquent areas of the brain that should be protected during surgery, and employ as a research tool to better understand the neurobiologic processes underlying normal and abnormal brain performance. (Chen)
- Neurostimulation coupled with electrophysiologic recording techniques may provide biomarkers for disease states that could be modulated by non-invasive neuromodulation, or even stand-alone biomarkers. (Rotenberg)
NOTE: The points in this list were made by the individual speakers identified above; they are not intended to reflect a consensus among workshop participants.
The effects of non-invasive neuromodulation provide not only potential therapeutic benefits, but also a window into the workings of the human brain. Thus, non-therapeutic uses of neuromodulation are being developed in parallel with therapeutic devices as research tools and for diagnosis and presurgical mapping to protect eloquent brain areas from damage during surgery.
Unlike therapeutic modalities of TMS, which use repetitive stimulation, diagnostic applications of TMS typically involve single-, paired-, or multiple-pulse techniques that enable the measurement of motor evoked potential (MEP) amplitude, central motor conduction time (CMCT), and cortical inhibition and excitation. As summarized by Robert Chen, professor of medicine at the University of Toronto, CMCT is used to detect myelopathy, upper motor neuron involvement in ALS, and the location of spinal cord lesions, and to document lesions in multiple sclerosis. In ALS, multiple TMS measures may be used to better characterize the disease. For example, in patients with ALS, motor cortex excitability may be increased while CMCT is typically delayed. These measures can thus be used to distinguish ALS from mimic disorders such as Kennedy’s disease or spinal muscular atrophy, or other neuromuscular disorders (Vucic et al., 2011). In addition, cortical hyperexcitability appears to be an early feature of ALS; thus it may be useful as a diagnostic biomarker (Vucic et al., 2011). TMS techniques may also enable the assessment of disease progression and treatment effectiveness in drug trials (Vucic et al., 2013).
Assessment of cortical inhibition with TMS may also be useful to predict response to acetylcholinesterase inhibitors in patients with Alzheimer’s disease (AD) (Di Lazzaro et al., 2005) and as a possible biomarker of mild cognitive impairment in patients with PD (Yarnall et al., 2013).
During surgery for brain tumors, arteriovenous malformation, epilepsy, or other brain conditions, surgeons often rely on mapping of the motor cortex to identify eloquent areas of the brain such as the speech area so they can avoid damage to those areas. TES has been used for this purpose, although it can only be done intraoperatively. However, Chen described recent studies using TMS presurgically to map the motor cortex; those studies indicate that this approach reliably predicts TES responses (Galloway et al., 2013; Krieg et al., 2013; Picht et al., 2013).
NEUROMODULATION AS A RESEARCH TOOL
Chen also described how TMS and tDCS are being widely used in both human and animal studies to gain a better understanding of the neurobiologic processes underlying normal and abnormal brain performance. For example, Vesia et al. (2010) used TMS to disrupt cortical activity in normal human volunteers, thus creating “virtual lesions” that identified the specific areas responsible for performing saccade (eye movement) and reach tasks, and Chen’s group has used TMS to study the physiologic underpinnings of levodopa-induced dyskinesias in individuals with PD (Morgante et al., 2006). These studies suggest that cortical plasticity is deficient in PD patients, particularly in dyskinetic patients. Chen’s group has also shown that plasticity can be restored with subthalamic nucleus deep brain stimulation (Kim et al., in press; Udupa and Chen, 2013).
Alexander Rotenberg noted that because stimulating a part of the brain can evoke a measurable response, neurostimulation coupled with electrophysiologic recording techniques may provide biomarkers for disease states that could be modulated neurostimulation, or even serve as stand-alone biomarkers.
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