Objectives

Electric stimulation is used to treat a number of neurologic disorders such as epilepsy and depression. However, delivering the required current to far-field neural targets is often ineffective because of current spread through low-impedance pathways. Here, the specific aims are to develop an empirical measure for current passing through the human head and to optimize stimulation strategies for targeting deeper structures, including the auditory nerve, by utilizing the cochlear implant (CI).

Materials and methods

Outward input/output (I/O) functions were obtained by CI stimulation and recording scalp potentials in five CI subjects. Conversely, inward I/O functions were obtained by noninvasive transcranial electric stimulation (tES) and recording intracochlear potentials using the onboard recording capability of the CI.

Results

I/O measures indicate substantial current spread, with a maximum of 2.2% gain recorded at the inner ear target during tES (mastoid-to-mastoid electrode configuration). Similarly, CI stimulation produced a maximum of 1.1% gain at the scalp electrode nearest the CI return electrode. Gain varied with electrode montage according to a point source model that accounted for distances between the stimulating and recording electrodes. Within the same electrode montages, current gain patterns varied across subjects suggesting the importance of tissue properties, geometry, and electrode positioning.

Conclusion

These results provide a novel objective measure of electric stimulation in the human head, which can help to optimize stimulation parameters that improve neural excitation of deep structures by reducing the influence of current spread.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Noninvasive transcranial or minimally invasive transtympanic electric stimulation may offer a desirable treatment option for tinnitus because it can activate the deafferented auditory nerve fibers while posing little to no risk to hearing. Here, we built a flexible research interface to generate and control accurately charge-balanced current stimulation as well as a head-mounted instrument capable of holding a transtympanic electrode steady for hours. We then investigated the short-term effect of a limited set of electric stimulation parameters on tinnitus in 10 adults with chronic tinnitus. The preliminary results showed that 63% of conditions of electric stimulation produced some degree of tinnitus reduction, with total disappearance of tinnitus in six subjects in response to at least one condition. The present study also found significant side effects such as visual, tactile, and even pain sensations during electric stimulation. In addition to masking and residual inhibition, neuroplasticity is likely involved in the observed tinnitus reduction. To translate the present electric stimulation into a safe and effective tinnitus treatment option, we need to optimize stimulation parameters that activate the deafferented auditory nerve fibers and reliably suppress tinnitus, with minimal side effects and tolerable sensations. Noninvasive or minimally invasive electric stimulation can be integrated with sound therapy, invasive cochlear implants, or other forms of coordinated stimulation to provide a systematic strategy for tinnitus treatment or even a cure.

Noninvasive transcranial electric stimulation is increasingly being used as an advantageous therapy alternative that may activate deep tissues while avoiding drug side-effects. However, not only is there limited evidence for activation of deep tissues by transcranial electric stimulation, its evoked human sensation is understudied and often dismissed as a placebo or secondary effect. By systematically characterizing the human sensation evoked by transcranial alternating-current stimulation, we observed not only stimulus frequency and electrode position dependencies specific for auditory and visual sensation but also a broader presence of somatic sensation ranging from touch and vibration to pain and pressure. We found generally monotonic input-output functions at suprathreshold levels, and often multiple types of sensation occurring simultaneously in response to the same electric stimulation. We further used a recording circuit embedded in a cochlear implant to directly and objectively measure the amount of transcranial electric stimulation reaching the auditory nerve, a deep intercranial target located in the densest bone of the skull. We found an optimal configuration using an ear canal electrode and low-frequency (<300 Hz) sinusoids that delivered maximally ~1% of the transcranial current to the auditory nerve, which was sufficient to produce sound sensation even in deafened ears. Our results suggest that frequency resonance due to neuronal intrinsic electric properties need to be explored for targeted deep brain stimulation and novel brain-computer interfaces.

While noninvasive brain stimulation is convenient and cost effective, its utility is limited by the substantial distance between scalp electrodes and their intended neural targets in the head. The tympanic membrane, or eardrum, is a thin flap of skin deep in an orifice of the head that may serve as a port for improved efficiency of noninvasive stimulation. Here we chose the cochlea as a target because it resides in the densest bone of the skull and is adjacent to many deep-brain-stimulation structures. We also tested the hypothesis that noninvasive electric stimulation of the cochlea may restore neural activities that are missing in acoustic stimulation. We placed an electrode in the ear canal or on the tympanic membrane in 25 human adults (10 females) and compared their stimulation efficiency by characterizing the electrically-evoked auditory sensation. Relative to ear canal stimulation, tympanic membrane stimulation was four times more likely to produce an auditory percept, required eight times lower electric current to reach the threshold and produced two-to-four times more linear suprathreshold responses. We further measured tinnitus suppression in 14 of the 25 subjects who had chronic tinnitus. Compared with ear canal stimulation, tympanic membrane stimulation doubled both the probability (22% vs. 55%) and the amount (-15% vs. -34%) of tinnitus suppression. These findings extended previous work comparing evoked perception and tinnitus suppression between electrodes placed in the ear canal and on the scalp. Together, the previous and present results suggest that the efficiency of conventional scalp-based noninvasive electric stimulation can be improved by at least one order of magnitude via tympanic membrane stimulation. This increased efficiency is most likely due to the shortened distance between the electrode placed on the tympanic membrane and the targeted cochlea. The present findings have implications for the management of tinnitus by offering a potential alternative to interventions using invasive electrical stimulation such as cochlear implantation, or other non-invasive transcranial electrical stimulation methods.

Although, green tea has numerous health benefits, adverse effects with excessive consumption have been reported. Using Drosophila melanogaster, a decrease in male fertility with green tea was evidenced. Here, the extent of green tea toxicity on development and reproduction was investigated. Drosophila melanogaster embryos and larvae were exposed to various doses of green tea polyphenols (GTP). Larvae exposed to 10 mg/mL GTP were slower to develop, emerged smaller, and exhibited a dramatic decline in the number of emerged offspring. GTP protected flies against desiccation but sensitized them to starvation and heat stress. Female offspring exhibited a decline in reproductive output and decreased survival while males were unaffected. GTP had a negative impact on reproductive organs in both males and females (e.g., atrophic testes in males, absence of mature eggs in females). Collectively, the data show that high doses of GTP adversely affect development and reproduction of Drosophila melanogaster.

Although, green tea has numerous health benefits, adverse effects with excessive consumption have been reported. Using Drosophila melanogaster, a decrease in male fertility with green tea was evidenced. Here, the extent of green tea toxicity on development and reproduction was investigated. Drosophila melanogaster embryos and larvae were exposed to various doses of green tea polyphenols (GTP). Larvae exposed to 10 mg/mL GTP were slower to develop, emerged smaller, and exhibited a dramatic decline in the number of emerged offspring. GTP protected flies against desiccation but sensitized them to starvation and heat stress. Female offspring exhibited a decline in reproductive output and decreased survival while males were unaffected. GTP had a negative impact on reproductive organs in both males and females (e.g., atrophic testes in males, absence of mature eggs in females). Collectively, the data show that high doses of GTP adversely affect development and reproduction of Drosophila melanogaster.