Clinical NeuroscienceEffect of individual anatomy on resting motor threshold – Computed electric field as a measure of cortical excitability
Highlights
► The motor threshold (MT) in transcranial magnetic stimulation (TMS) exhibits large variation between subjects possibly due to anatomical differences. ► Individual coil-to-cortex distance was measured and the TMS-induced electric field modelled at the cortex. ► Individual anatomy did not affect the MT in healthy subjects. ► Cortical electric field can be used as measure of motor excitability.
Introduction
Transcranial magnetic stimulation (TMS) is a non-invasive method for studying the function of cortical neurons and corticospinal pathways (Barker et al., 1985). In TMS, a rapidly modulated electric current is directed in a stimulation coil, which induces a magnetic field that penetrates the skull and the soft tissues of the head in a painless manner. Concurrently, an electric field is induced in the cortical neurons which, when sufficient in strength, results in the generation of an action potential. When the stimulus is targeted to the primary motor cortex (M1), it produces a motor evoked potential (MEP) in the peripheral muscle corresponding to the stimulated cortical representation area (Fatemi-Ardekani, 2008, Terao and Ugawa, 2002). TMS can be used for studying various aspects of corticospinal excitability, with motor excitability being the most widely used, since MEPs are suitable for objective monitoring by electromyography (EMG) (Caramia et al., 1989, Rossini et al., 1991). The level of individual corticospinal excitability is commonly determined by the motor threshold (MT). In a relaxed muscle, the MT is often defined as the lowest stimulation intensity that produces MEPs over 50 μV in amplitude in 50% of trials (Rossini et al., 1994). The determination of the individual MT is a fundamental procedure in most TMS-studies, since it provides a baseline parameter of excitability, to which other TMS measurements are proportioned. As the MT is traditionally reported as a percentage of maximum stimulator output (%-MSO), it is dependent on the applied instrumentation, which complicates direct comparison with results obtained with different stimulator types. Furthermore, the MT displays extensive variability, both between and within subjects (Danner et al., 2008, Kimiskidis et al., 2004, Koski et al., 2005, Mills and Nithi, 1997, Säisänen et al., 2008, Wassermann, 2002). However, it has not been extensively characterized to which extent the variation of the MT derives from methodological and anatomical factors as opposed to physiological variation of cortical excitability.
As the strength of the TMS-generated magnetic field decreases in proportion to the distance from the stimulation coil, the electric field induced in the cortex depends on the distance between the coil and the cortex (Ruohonen and Ilmoniemi, 1999) (Fig. 1). Therefore, the individual scalp-to-cortex distance can be considered as an important anatomical determinant of the clinical effect of TMS. Since scalp-to-cortex distance is the major contributor to the distance between the stimulation coil and the eloquent cortex, it will partially define the stimulus intensity required for the generation of MEPs, and consequently be reflected in the MT estimates (Herbsman et al., 2009, Kozel et al., 2000, McConnell et al., 2001, Stokes et al., 2005, Stokes et al., 2007). Accordingly, the between-subject variation of the MT has been reported to be greater than the within-subject variation (Danner et al., 2008, Kimiskidis et al., 2004, Koski et al., 2005, Mills and Nithi, 1997, Säisänen et al., 2008, Wassermann, 2002). In addition to the anatomical variation, inaccurate positioning of the stimulation coil may affect the properties of the induced electric field in the brain, since changes in the location, orientation or tilting of the coil on the scalp may be responsible for significant changes in the distance between the coil and the targeted cortical area (Conforto et al., 2004, Knecht et al., 2005, Maccabee et al., 1993, Mills et al., 1992).
It is crucially important to be aware of and account for the methodological and anatomical factors contributing to the variation of the MT in order to reliably evaluate the physiological variation of cortical excitability. Therefore the present study was designed to minimize the variation caused by coil positioning by using navigated TMS which can be utilized to stabilize the coil position, orientation and tilting throughout the stimulation procedure (Hannula et al., 2005, Julkunen et al., 2009). The TMS-induced electric field in the brain can be estimated computationally by using a navigation system. The location of the maximum electric field strength is assumed to be at the centre of the area where cortical motor neurons are activated and thus regarded as the target of the stimulation (Ruohonen and Karhu, 2010). We aimed to reduce the between-subject variation of the MT by utilizing an electric field estimate in the motor cortex computed at stimulation intensity corresponding to the MT. Hypothetically, the electric field estimate should be independent of subject anatomy and the instrumentation used, and consequently, it should reduce the anatomical and methodological variation in cortical excitability measurements.
Section snippets
Subjects
Fifty-five volunteers participated in the study. The data was gathered from our previous study conducted with a population with a wider age-range (Säisänen et al., 2008). Five subjects were excluded from the 55 subjects, as sufficiently high stimulation intensity for MT determination could not be achieved with monophasic stimulation. Thus, the final study population consisted of fifty subjects (24 male and 26 female, age 44 ± 14 years, range 22–69 years). The subjects had no neurological
Results
All parameters of corticospinal excitability (MT, EF25 mm and EFcortex) correlated significantly with each other (p < 0.001). There was a significant correlation between the hemispheres (p < 0.001) with no interhemispheric differences being observed. All the parameters exhibited also similar variations, with coefficients of variation ranging from 18% to 22% (Table 1). In the 5 subjects who were excluded from the analyses due to indeterminable MT with monophasic stimulation on either or both
Discussion
The maximum computational electric field on the cortex is a purposeful measure of motor excitability, as it is a direct estimate of the stimulation intensity required to produce activation in cortical neurons. Ideally, it should be independent of individual anatomy and would permit a comparison of results from different studies conducted with different stimulation systems. In the current study, EFcortex exhibited remarkable concordance with the traditional, instrumentation-dependent MT as well
Financial disclosures
Petro Julkunen and Laura Säisänen have received consulting fees, unrelated to this study, from Nexstim Ltd., manufacturer of navigated TMS systems.
Acknowledgements
Nils Danner has received funding for the study from The Cultural Foundation of Northern Savo, The Epilepsy Research Foundation, The Emil Aaltonen Foundation and The Finnish Medical Society Duodecim.
References (43)
TMS and threshold hunting
Suppl Clin Neurophysiol
(2003)- et al.
Non-invasive magnetic stimulation of human motor cortex
Lancet
(1985) - et al.
Electric vs magnetic trans-cranial stimulation of the brain in healthy humans: a comparative study of central motor tracts ‘conductivity’ and ‘excitability’
Brain Res
(1989) - et al.
Impact of coil position and electrophysiological monitoring on determination of motor thresholds to transcranial magnetic stimulation
Clin Neurophysiol
(2004) - et al.
Navigated transcranial magnetic stimulation and computed electric field strength reduce stimulator-dependent differences in the motor threshold
J Neurosci Methods
(2008) - et al.
Human brain connectivity during single and paired pulse transcranial magnetic stimulation
Neuroimage
(2011) - et al.
Threshold curves for transcranial magnetic stimulation to improve reliability of motor pathway status assessment
Clin Neurophysiol
(2011) - et al.
Comparison of navigated and non-navigated transcranial magnetic stimulation for motor cortex mapping, motor threshold and motor evoked potentials
Neuroimage
(2009) - et al.
The repeatability of corticomotor threshold measurements
Neurophysiol Clin
(2004) - et al.
Scalp position and efficacy of transcranial magnetic stimulation
Clin Neurophysiol
(2005)
Normative data on changes in transcranial magnetic stimulation measures over a ten hour period
Clin Neurophysiol
The transcranial magnetic stimulation motor threshold depends on the distance from coil to underlying cortex: a replication in healthy adults comparing two methods of assessing the distance to cortex
Biol Psychiatry
Magnetic brain stimulation with a double coil: the importance of coil orientation
Electroencephalogr Clin Neurophysiol
Effects of aging on motor cortex excitability
Neurosci Res
Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application. Report of an IFCN committee
Electroencephalogr Clin Neurophysiol
Brain excitability and electroencephalographic activation: non-invasive evaluation in healthy humans via transcranial magnetic stimulation
Brain Res
Navigated transcranial magnetic stimulation
Neurophysiol Clin
Elucidating the mechanisms and loci of neuronal excitation by transcranial magnetic stimulation using a finite element model of a cortical sulcus
Clin Neurophysiol
Distance-adjusted motor threshold for transcranial magnetic stimulation
Clin Neurophysiol
Variation in the response to transcranial magnetic brain stimulation in the general population
Clin Neurophysiol
Characterisation of paired-pulse transcranial magnetic stimulation conditions yielding intracortical inhibition or I-wave facilitation using a threshold-hunting paradigm
Exp Brain Res
Cited by (30)
Higher motor cortical excitability linked to greater cognitive dysfunction in Alzheimer's disease: results from two independent cohorts
2021, Neurobiology of AgingCitation Excerpt :For the multiple regression models, we assessed factors that might affect the association between ADAS-Cog and RMT. Age, SCD, gender, handedness, and ROI-based left motor cortex thickness were included since they are known to be associated with cognition and/or TMS measurements of cortical excitability (Danner et al., 2012; Sollmann et al., 2017). APOE polymorphisms were included since having one or more ε4 alleles increases the risk of developing AD (Petersen et al., 1996).
Simultaneously applying cathodal tDCS with low frequency rTMS at the motor cortex boosts inhibitory aftereffects
2019, Journal of Neuroscience MethodsFunctional and structural cortical characteristics after restricted focal motor cortical infarction evaluated at chronic stage - Indications from a preliminary study
2016, Clinical NeurophysiologyCitation Excerpt :Alternatively, the observed changes in SICI in the AH could be due to changes in the composition of the corticospinal volley evoked by TMS after stroke. Measures of motor cortical excitability (e.g. MT) are influenced also by anatomical factors, such as the coil-to-cortex distance affected by distance of scalp from the stimulated cortex (Danner et al., 2012; Julkunen et al., 2012a). In addition, the anatomical neuronal organization and macrostructure may affect the measures of excitability (Janssen et al., 2013, 2014; Kallioniemi et al., 2015b).