###### Abstract  
Compared to the existing noninvasive methods, temporal interference (TI) current stimulation is an emerging noninvasive neuromodulation technique that can improve the ability to focus an electrical field on a target nerve. Induced TI field distribution depends on the anatomical structure of individual neurons, and thus the electrode and current optimization to enhance the field focus must reflect these factors. The current study presents a TI field optimization framework for focusing the stimulation energy on the target tibial nerve through extensive electrical simulations, factoring in individual anatomical differences. We conducted large-scale in-silico experiments using realistic models based on magnetic resonance images of human subjects to evaluate the effectiveness of the proposed methods for tibial nerve stimulation considering overactive bladder (OAB) treatment. The electrode position and current intensity were optimized for each subject using an automated algorithm, and the field-focusing performance was evaluated based on the maximum intensity of the electric fields induced at the target nerve compared with the electric fields in the neighboring tissues. Using the proposed optimization framework, the focusing ability increased by 12% when optimizing the electrode position. When optimizing both the electrode position and current, this capability increased by 11% relative to electrode position optimization alone. These results suggest the significance of optimizing the electrode position and current intensity for focusing TI fields at the target nerve. Our electrical simulation-based TI optimization framework can be extended to enable personalized peripheral nerve stimulation therapy to modulate peripheral nerves. temporal interference stimulation; tibial nerve stimulation; noninvasive neurostimulation; overactive bladder syndrome; simulation based on MR image +
Footnote †: journal: Applied Sciences  
clinical treatments for OAB has received global attention. Conventional therapies based on medications such as antimuscarinic or anticholinergic agents remain the primary treatment options for OAB [3]. However, these methods are known to cause severe side effects such as dry mouth, blurred vision, constipation, and urine retention [4,5]. A few recent studies have reported that pharmacotherapies fail to relieve OAB symptoms in 46.2% of patients, who then decide to discontinue treatment [6,7]. To overcome the current limitations of pharmaceutical approaches, neurostimulation targeting peripheral nerves was suggested as an alternative treatment based on etiological evidence that neurological dysfunction induces OAB [8, 9, 10]. Neurostimulation modalities such as sacral nerve stimulation (SNS) using an implantable neuroprosthetic device [11], and percutaneous tibial nerve stimulation (PTNS) using invasive needle electrodes, have been clinically used for treating refractory OAB in patients experiencing pharmacotherapy side effects [11, 12, 13, 14]. However, due to their invasive nature, they can cause significant discomfort and carry procedural risks such as the spreading of infections [15]. In this regard, transcutaneous electrical nerve stimulation (TENS) has been proposed as a noninvasive modality [16, 17]. While TENS has gained considerable attention owing to the significant advantage of noninvasiveness, it is considered less effective than the invasive modalities due to its low penetration efficiency and reduced coupling of stimulation current into the body [18]. Due to this low penetration efficiency, side effects such as redness, skin burns, and pain associated with electrical stimulation have been reported after increasing the stimulation intensity during TENS [16]. Therefore, the development of a noninvasive modality with a high penetration rate is one of the most important challenges in enhancing the effectiveness of noninvasive neurostimulation methods to treat OAB [19].