Review ArticleFundamentals of transcranial electric and magnetic stimulation dose: Definition, selection, and reporting practices
Section snippets
Basic principles of EM stimulation
Though there remain many questions about the mechanisms of neuromodulation by transcranial EM stimulation, fundamentally, stimulation affects neural activity and ultimately behavior through the generation of an electric field and associated electrical currents (current density field) in the head.6, 7 There is evidence that neural activity may also be affected by static magnetic fields.8 Therefore, in our general discussion we refer to an electromagnetic field which subsumes the electric,
Electromagnetic field generation
All transcranial EM stimulation devices consist of two main components: (1) a waveform generator and (2) electrodes or an electromagnet coil positioned on the head. The waveform generator delivers electrical current to the electrodes or coil. In transcranial electric stimulation, scalp surface electrodes inject currents through the head, whereas in magnetic stimulation, currents are induced within the head by the coil. In both cases the result is an electric field (measured in volt/meter or
Biologic effects of EM brain stimulation
The current state of knowledge of the physiologic mechanisms of transcranial EM brain stimulation remains limited. Recent reviews provide valuable summaries of current understanding.38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 We briefly discuss the fundamental aspects of the interaction between electromagnetic fields and neural tissue to establish a rational definition of EM stimulation dose.
At present, it is understood that the main mechanism by which electromagnetic field of the
Dose definition and dose selection
Figure 3 and Table 1 summarize the process of dosing transcranial EM stimulation. The researcher/clinician chooses an EM stimulation device and its settings based on subject-independent knowledge (e.g., scientific hypothesis, mechanisms of action, etiology of disorder, prior research/clinical experience, computational models) and subject-specific data (e.g., age, sex, structural and diffusion MRI, diagnosis, risk factors, treatment history, individual electromagnetic field model, prior EM
Dose parameters
Reporting of EM stimulation dose should be guided by the principle of reproducibility: sufficient information about the stimulation parameters should be provided so that the stimulation dose can be independently replicated or modeled based on this description. No aspect of the EM stimulation device configuration that affects the electromagnetic field should be omitted because the researcher/clinician considers it unimportant for outcome, as subsequent interpretations of the results could
Stimulus waveform generator parameters
The stimulus waveform refers to the current and/or voltage waveform generated by the stimulation source and applied to the stimulating electrodes or coil (see Figure 2 for some examples). The stimulus waveform governs the temporal variation of the electromagnetic field during the stimulation session. For a particular EM stimulation device, some waveform parameters may be fixed, whereas others may be user-adjustable over a given range. The principle of reproducibility dictates that when
Electrode and coil parameters
Another component of the transcranial EM stimulation dose refers to the dimensions, materials, and position of the electrodes or coil. Typically commercial electrodes or coils are used, in which case the manufacturer and part number should be provided in addition to basic information about the electrode/coil physical characteristics. Placement of the electrodes or coil is controlled by the researcher/clinician and should be carefully documented and reported, specifying how the placement was
Measuring/verifying dose
As defined previously, the EM stimulation dose is comprised of the device parameters that affect the electromagnetic field in the brain. Therefore, the EM dose corresponding to particular device configuration and settings can be calibrated and verified independent of the presence of a subject. As stimulation devices remain in use over periods of years and as faults can compromise safety and reproducibility, a basic level of verification and vigilance is warranted. The waveform generator,
Summary metrics
Summary metrics (also known as “composite parameters”4) are defined as quantities that are a function of two or more EM stimulation dose parameters.5 Examples include average electrode current density (defined as electrode current divided by electrode area), which is sometimes used in tDCS and tACS,92 charge per pulse phase that is used to define safety limits,103, 104 and charge rate and total stimulus charge or energy that are used in ECT.12, 105 Summary metrics reduce the information content
Dose selection
Dose selection includes all steps that inform the choice of transcranial EM stimulation dose to be delivered.
Individual anatomic and physiologic data
All relevant, available subject/patient data should be considered in determining the EM dose. These include any biologic factors that affect the stimulation outcome including subject anatomical data (affecting the electromagnetic field distribution; refer to “Electromagnetic field generation”) and physiology (affecting responses to the electromagnetic field; refer to “Biologic effects of EM brain stimulation”). Relevant patient data may include disease cause and information on additional
Dosing relative to individual measures
Transcranial EM stimulation dose is often individualized based on physiologic, cognitive, or behavioral measures. For example, the EM dose may be adjusted relative to evoked physiologic responses and/or a clinical outcome. The motivation for the use of relative dosing is that the absolute EM dose does not fully determine outcome because of variability across individuals. Indeed, a functional measure may be perceived as more accurate than absolute measures because it reflects the net sum of
EM field models
Because the effects of transcranial EM stimulation are thought to result chiefly from the electric and current density fields generated in the head, knowledge of the electric/current density field characteristics can help to select the dose for and/or to interpret a study or a treatment using EM stimulation, and can be useful in optimizing stimulation techniques. There are presently no established techniques for noninvasively measuring in vivo the electric/current density field distribution in
Safety considerations in EM dose determination
Risk/benefit considerations override other aspects of dose selection, and are in the realm of clinical decision making beyond the scope of this paper. After consideration of subject specific risk factors, controlling the EM dose is the primary method to address safety concerns. Conversely, without controlling and documenting the EM dose, it is impossible to ensure subject safety and to accumulate safety data that can inform the development of safety guidelines.
The ability to draw safety
Device artifacts and environmental factors
As discussed in the section on biologic effects of EM brain stimulation, besides effects on neural activity resulting from the intracerebral electromagnetic field, transcranial EM stimulation paradigms may affect brain function via direct extracranial nerve and muscle stimulation and nonelectromagnetic interactions such as sound and scalp pressure. Direct activation of extracranial nerves and muscles is inherently encompassed by the EM dose description, since the EM dose parameters determine
Conclusion
In 2011, there remains no standard for reporting transcranial EM brain stimulation protocols, and adequate information for study reproduction is often omitted. That is a surprising state given that this concept is not new to the literature. In 1988, Weiner and colleagues4 reported that in ECT literature, dose “frequently is not adequately presented to allow the reader to understand the nature and intensity of stimulation delivered” and cited Ulett who, in 1952, complained that from the
Acknowledgments
We thank Mr. Won Hee Lee for creating Figure 1.
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Cited by (0)
Dr. Peterchev is inventor on Columbia University patents and patent applications on TMS and MST technology licensed to Rogue Research; he has received a research grant from Rogue Research and equipment donations from Magstim, MagVenture, and ANS/St. Jude Medical; he is also supported by NIH grant R01MH091083 and Wallace H. Coulter Foundation Translational Partners grant. Dr. Wagner is the Chief Science Officer of Highland Instruments, a medical device company; he has multiple patents pending related to imaging, brain stimulation, and wound healing. Dr. Miranda is inventor on patents and patent applications on TMS. Dr. Nitsche reported no biomedical financial interests or conflicts of interest. Dr. Paulus is member of the Medical and Scientific advisory board of EBS technologies, and has received equipment support from NeuroConn, Magstim, and MagVenture. Dr. Lisanby has served as Principal Investogator on industry-sponsored research grants to Columbia/RFMH or Duke (Neuronetics [past], Brainsway, ANS/St. Jude Medical, Cyberonics [past]); equipment loans to Columbia or Duke (Magstim, MagVenture); is coinventor on a patent application on TMS technology; is supported by grants from National Institutes of Health (R01MH091083-01, 5U01MH084241-02, 5R01MH060884-09), Stanley Medical Research Institute, and National Alliance for Research on Schizophrenia and Depression; and has no consultancies, speakers bureau memberships, board affiliations, or equity holdings in related industries. Dr. Pascual-Leone serves on the scientific advisory board of Starlab, Neuronix, Nexstim, and Neosync, and holds intellectual property on the integration of TMS with EEG and MRI; he was supported by grants from the National Center for Research Resources: Harvard-Thorndike General Clinical Research Center at BIDMC (NCRR MO1 RR01032) and Harvard Clinical and Translational Science Center (UL1 RR025758), NIH grant K24 RR018875 and grants from the R. J. Goldberg Foundation, Nancy Lurie Marks Family Foundation, and Michael J. Fox Foundation. Dr. Bikson is inventor on multiple patents on brain stimulation technology (CUNY) and is co-founder of Soterix Medical Inc.; and is supported by grant from the Wallace H. Coulter Foundation and NIH (NIGMS 41341-03-30, NIMH 41771-00-01).