## 4 Electroceticals--Intelligent Environments
### Vagus Nerve Stimulation  
The vagus nerve consists of a heterogeneous group of neural fibers innervating numerous organs. Vagus nerve stimulator (VNS) broadly stimulates the connected heterogeneous fibers. It is a neuromodulation system that can be implantable and consists of a pulse generator implanted under the skin near the chest [120]. It runs lead wires up to an electrode cuff wrapped around the cervical bundle of the left vagus nerve [120]. [PERSON] first introduced it in 1980 and experimentally proved antiepileptic effects [121]. Globally, many patients had a vagus nerve stimulator system implanted in their bodies [121] for treating epilepsy, depression, and migraines [122; 123; 124; 125]. It is under investigation for treating pathological conditions such as motor impairment after heart stroke and tinnitus [126]. The VNS system's first controlled clinical trials were conducted in 1990 to treat refractory epilepsy. Though a significant proportion of patients did not display symptomatic improvement, clinical observational studies of the device showed a substantial reduction in seizure frequency [127; 128]. Following the number of further clinical trials, observational studies and subsequent analysis led to the approval of VNS by the FDA in 2005 to treat pharmaco-resistant depression [129; 130]. More recently, VNS has been evaluated and suggested as an alternative for treating a diverse array of disorders, including sepsis [131; 132], heart failure [121; 133], bowel disease [134], chronic pain [135], and rheumatoid arthritis inflammatory [136]. ElectroCore (Rockaway, NJ, USA) introduced GammaCore (nVNS), a noninvasive VNS, also referred to as the transcutaneous VNS (taVNS), is the most widely available device [137]. This handheld device could deliver alternating sinusoidal current with a broadband amplitude modulated frequency spectrum. In 2017 in USA., this device received FDA approval for treating acute cluster headache, and in 2018 the device received support for treating adjunctive cluster headache and acute migraine treatment [137]. Furthermore, NEMOS transcutaneous auricular vagus nerve stimulator (taVNS) is another one developed by Cerbomed GmbH, Erlangen, Germany. It is the most widely used commercially available taVNS device that could deliver current in rhythmic square pulses [138]. In 2010, this device received European certification for treating epilepsy and depression, in 2012 for chronic pain, and in 2019 for anxiety [138]. VNS devices developed companies are listed in Table 1.  
Although the peripheral and central nervous systems via electrical stimulation have attracted much attention due to their potential advantages on neuropsychiatric diseases, its non-cell type-specific activation characteristics could hinder its wide clinical applications. Therefore, optogenetic approaches have attracted more recently and been applied as a cell-specific approach to the vagus nerve for precise modulation of neural functions [139]. The commonly used optical waveguides are silica optical fibers that could help stimulate the vagus nerve optogenetically. [PERSON] et al. successfully developed a simplified method for fabricating flexible and stretchable polymer optical fibers as optical waveguides [PERSON] et al. (2018). Significant advantages of these fabricated polymer optical fibers are low young modulus, high stretchability, improved biocompatibility, and long-term stability. These important response characteristics suggest the optical fiber's capability to implement in vivo optogenetic applications. To determine whether these polymer optical fibers could deliver enough light to modulate optogenetically in vivo, an adeno-associated virus was injected into the mouse hippocampus of mice. Subsequently, a custom-made opto-electrode array consisting of polymer optical fibers and two tetrodes was used to stimulate and record electrophysiological activities.