# Electric Field Distribution Induced by TMS: Differences Due to Anatomical Variation
## 1 Introduction  
### TMS Principles, Parameters and Applications  
Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation (NIBS) technique that is widely used as a research, diagnostic, and therapeutic tool in health and disease [1]. As first demonstrated by [PERSON] and [PERSON] [2], almost 40 years ago, TMS stimulates the human brain by inducing intracranial eddy currents, based on the phenomenon of electromagnetic induction [3]. Since then, the technique has evolved to a valuable brain mapping tool [4; 5] as well as a useful therapeutic option in a wide range of neurological and psychiatric disorders [6], including depression [7], obsessive compulsive disorder (OCD) [8], addictions [9], dementia [10], epilepsy [11], [PERSON]'s and Parkinson's diseases, and brain impairment caused by stroke or tumors [12].  
TMS is painless and relatively easy to use in the clinical environment. In short, an electromagnetic coil, placed over the scalp and connected to a magnetic stimulator, generates a rapidly altering magnetic field, thereby inducing an electric field (EF) inbrain tissue. The technique is applied either as a single pulse or as a train of multiple pulses (rTMS--repetitive transcranial magnetic stimulation) that, depending on the exact paradigm, can either stimulate or inhibit cortical neurons and modulate accordingly their excitability [12]. The brain's response to TMS can be detected in various ways but principally through electromyographic (TMS-EMG) or electroencephalographic (TMS-EEG) recordings [13].  
The efficacy of TMS interventions is based on multiple parameters that fall into three main categories, i.e., they are related to the coil, the stimulus, and the brain. The physical properties of the electromagnetic coil, i.e., its shape and dimensions [14], define the depth of stimulation and the volume of the stimulated area [3]. Generally, larger coils are used in order to cover more extensive targets [15], while smaller ones achieve higher locality [16]. The coil's exact position over the scalp is particularly relevant for the outcome of stimulation [17], as the orientation of the coil relative to the underlying sulcus affects the induced EF distribution [18], with the vertical relative position being the optimal one, as it is reported that typical targets, such as the motor cortex, are most sensitive to vertically oriented electric fields. The stimulus characteristics, i.e., its magnitude, density, and duration, as well as the waveform of the magnetic pulse, also constitute critical parameters for the method's efficiency [19], which is additionally affected by the geometry and electrical properties of the brain tissue [20]. However, due to the complexity of neurobiological phenomena and the diversity in human brain anatomy, the exact details of how TMS works remain vague [18]. One complementary approach that may provide valuable information about the mechanisms underlying TMS effects on the human brain is computational EF modeling [21; 22]. Thus, it is increasingly used to enhance the method's diagnostic potential and increase its therapeutic efficiency [23].