EMG-Free Monitorization of the Acoustic Startle Reflex with a Mobile Phone: Implications of Sound Parameters with Posture Related Responses.

(1) Background: Acute acoustic (sound) stimulus prompts a state of defensive motivation in which unconscious muscle responses are markedly enhanced in humans. The orbicularis oculi (OO) of the eye is an easily accessed muscle common for acoustic startle reaction/response/reflex (ASR) investigations and is the muscle of interest in this study. Although the ASR can provide insights about numerous clinical conditions, existing methodologies (Electromyogram, EMG) limit the usability of the method in real clinical conditions. (2) Objective: With EMG-free muscle recording in mind, our primary aim was to identify and investigate potential correlations in the responses of individual and cooperative OO muscles to various acoustic stimuli using a mobile and wire-free system. Our secondary aim was to investigate potential altered responses to high and also relatively low intensity acoustics at different frequencies in both sitting and standing positions through the use of biaural sound induction and video diagnostic techniques and software. (3) Methods: This study used a mobile-phone acoustic startle response monitoring system application to collect blink amplitude and velocity data on healthy males, aged 18-28 community cohorts during (n = 30) in both sitting and standing postures. The iPhone X application delivers specific sound parameters and detects blinking responses to acoustic stimulus (in millisecond resolution) to study the responses of the blinking reflex to acoustic sounds in standing and sitting positions by using multiple acoustic test sets of different frequencies and amplitudes introduced as acute sound stimuli (<0.5 s). The single acoustic battery of 15 pure-square wave sounds consisted of frequencies and amplitudes between 500, 1000, 2000, 3000, and 4000 Hz scales using 65, 90, and 105 dB (e.g., 3000 Hz_90 dB). (4) Results: Results show that there was a synchronization of amplitude and velocity between both eyes to all acoustic startles. Significant differences (p = 0.01) in blinking reaction time between sitting vs. standing at the high intensity (105 dB) 500 Hz acoustic test set was discovered. Interestingly, a highly significant difference (p < 0.001) in response times between test sets 500 Hz_105 dB and 4000 Hz_105 dB was identified. (5) Conclusions: To our knowledge, this is the first mobile phone-based acoustic battery used to detect and report significant ASR responses to specific frequencies and amplitudes of sound stimulus with corresponding sitting and standing conditions. The results from this experiment indicate the potential significance of using the specific frequency, amplitude, and postural conditions (as never before identified) which can open new horizons for ASR to be used for diagnosis and monitoring in numerous clinical and remote or isolated conditions.

Intrinsic Auricular Muscle Zone Stimulation Improves Walking Parameters of Parkinson's Patients Faster Than Levodopa in the Motion Capture Analysis: A Pilot Study.

It has been demonstrated that intrinsic auricular muscles zone stimulation (IAMZS) can improve the motor symptoms of Parkinson's disease (PD) patients who are examined with the Unified Parkinson's Disease Rating Scale (UPDRS) motor scores. In the present pilot study, using motion capture technology, we aimed to investigate the efficacy of IAMZS compared to medication alone or in combination with medication. Ten PD patients (mean age: 54.8 ± 10.1 years) were enrolled. Each participant participated in three different sessions: sole medication, sole stimulation-20 min of IAMZS, and combined IAMZS (20 min) and medication. Each session was performed on different days but at the same time to be aligned with patients' drug intake. Motion capture recording sessions took place at baseline, 20, 40, and 60 min. Statistical analysis was conducted using one-way repeated measures ANOVA. Bonferroni correction was implemented for pairwise comparisons. The sole medication was ineffective to improve gait-related parameters of stride length, stride velocity, stance, swing, and turning speed. In the sole-stimulation group, pace-related gait parameters were significantly increased at 20 and 40 min. These improvements were observed in stride length at 20 (p = 0.0498) and 40 (p = 0.03) min, and also in the normalized stride velocity at 40 min (p-value = 0.02). Stride velocity also tended to be significant at 20 min (p = 0.06) in the sole-stimulation group. Combined IAMZS and medication demonstrated significant improvements in all the time segments for pace-related gait parameters [stride length: 20 min (p = 0.04), 40 min (p = 0.01), and 60 min (p < 0.01); stride velocity: 20 min (p < 0.01), 40 min (p = 0.01), and 60 min (p < 0.01)]. These findings demonstrated the fast action of the IAMZS on PD motor symptoms. Moreover, following the termination of IAMZS, a prolonged improvement in symptoms was observed at 40 min. The combined use of IAMZS with medication showed the most profound improvements. The IAMZS may be particularly useful during medication off periods and may also postpone the long-term side effects of high-dose levodopa. A large scale multicentric trial is required to validate the results obtained from this pilot study. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03907007.

Improvement of Olfactory Function With High Frequency Non-invasive Auricular Electrostimulation in Healthy Humans.

In past literature on animal models, invasive vagal nerve stimulation using high frequencies has shown to be effective at modulating the activity of the olfactory bulb (OB). Recent advances in invasive vagal nerve stimulation in humans, despite previous findings in animal models, used low frequency stimulation and found no effect on the olfactory functioning. The present article aimed to test potential effects of non-invasive, high and low frequency vagal nerve stimulation in humans, with supplementary exploration of the orbitofrontal cortex using near-infrared spectroscopy (NIRS). Healthy, male adult participants (n = 18) performed two olfactory tests [odor threshold test (OTT) and supra-threshold test (STT)] before and after receiving high-, low frequency vagal nerve stimulation and placebo (no stimulation). Participant's olfactory functioning was monitored using NIRS, and assessed with two behavioral olfactory tests. NIRS data of separate stimulation parameters were statistically analyzed using repeated-measures ANOVA across different stages. Data from olfactory tests were analyzed using paired parametric and non-parametric statistical tests. Only high frequency, non-invasive vagal nerve stimulation was able to positively modulate the performance of the healthy participants in the STT (p = 0.021, Wilcoxon sign-ranked test), with significant differences in NIRS (p = 0.014, post-hoc with Bonferroni correction) recordings of the right hemispheric, orbitofrontal cortex. The results from the current article implore further exploration of the neurocircuitry involved under vagal nerve stimulation and the effects of non-invasive, high frequency, vagal nerve stimulation toward olfactory dysfunction which showcase in Parkinson's and Alzheimer's Diseases. Despite the sufficient effect size (moderate effect, correlation coefficient (r): 0.39 for the STT) of the current study, future research should replicate the current findings with a larger cohort.

Non-invasive High Frequency Median Nerve Stimulation Effectively Suppresses Olfactory Intensity Perception in Healthy Males.

Median nerve stimulation (MNS) had been performed in the existing literature to alleviate symptoms of nausea and vomiting. The observed facilitative effects are thought to be mediated by the vagal pathways, particularly the vagus nerve (VN) brainstem nuclei of the dorsal motor nucleus of vagus and nucleus tractus solitarius (DMV-NTS). Sense of smell is one of the major sensory modalities for inducing vomiting and nausea as a primary defense against potentially harmful intake of material. This study aimed to test effects of non-invasive, high and low frequency MNS on human olfactory functioning, with supplementary exploration of the orbitofrontal cortex (OFC) using near-infrared spectroscopy (NIRS). Twenty healthy, male, adults performed supra-threshold odor intensity tests (labeled magnitude scale, LMS) for four food-related odorant samples (presented in three different concentrations) before and after receiving high-, low frequency MNS and placebo (no stimulation), while cortical activities in the OFC was monitored by the NIRS. Data of the NIRS and LMS test of separate stimulation parameters were statistically analyzed using mixed-model analysis of variance (ANOVA). Only the high frequency MNS showed effects for suppressing the intensity perception of the moderate concentration of Amyl Acetate (p:0.042) and strong concentration of Isovaleric Acid (p:0.004) and 1-Octen-3-ol (p:0.006). These behavioral changes were coupled with significant changes in the NIRS recordings of the left (p:0.000) and right (p:0.003) hemispheric orbitofrontal cortices. This is the first study that applied non-invasive, high frequency MNS to suppress the supra-threshold odor ratings of specific concentrations of odors. The vagal networks are potential relays of MNS to influence OFC. Results from the current article implore further research into non-invasive, high frequency MNS in the investigation of its modulatory effects on olfactory function, given its potential to be used for ameliorating nausea and malnutrition associated with various health conditions.

Rapid Alleviation of Parkinson's Disease Symptoms via Electrostimulation of Intrinsic Auricular Muscle Zones.

Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) and the pedunculopontine nucleus (PPN) significantly improve cardinal motor symptoms and postural instability and gait difficulty, respectively, in Parkinson's disease (PD). Objective and Hypothesis: Intrinsic auricular muscle zones (IAMZs) allow the potential to simultaneously stimulate the C2 spinal nerve, the trigeminal nerve, the facial nerve, and sympathetic and parasympathetic nerves in addition to providing muscle feedback and control areas including the STN, the PPN and mesencephalic locomotor regions. Our aim was to observe the clinical responses to IAMZ stimulation in PD patients. Method: Unilateral stimulation of an IAMZ, which includes muscle fibers for proprioception, the facial nerve, and C2, trigeminal and autonomic nerve fibers, at 130 Hz was performed in a placebo- and sham-controlled, double-blinded, within design, two-armed study of 24 PD patients. Results: The results of the first arm (10 patients) of the present study demonstrated a substantial improvement in Unified Parkinson's Disease Ratings Scale (UPDRS) motor scores due to 10 min of IAMZ electrostimulation (p = 0.0003, power: 0.99) compared to the placebo control (p = 0.130). A moderate to large clinical difference in the improvement in UPDRS motor scores was observed in the IAMZ electrostimulation group. The results of the second arm (14 patients) demonstrated significant improvements with dry needling (p = 0.011) and electrostimulation of the IAMZ (p < 0.001) but not with sham electrostimulation (p = 0.748). In addition, there was a significantly greater improvement in UPDRS motor scores in the IAMZ electrostimulation group compared to the IAMZ dry needling group (p < 0.001) and the sham electrostimulation (p < 0.001) groups. The improvement in UPDRS motor scores of the IAMZ electrostimulation group (ΔUPDRS = 5.29) reached moderate to high clinical significance, which was not the case for the dry needling group (ΔUPDRS = 1.54). In addition, both arms of the study demonstrated bilateral improvements in motor symptoms in response to unilateral IAMZ electrostimulation. Conclusion: The present study is the first demonstration of a potential role of IAMZ electrical stimulation in improving the clinical motor symptoms of PD patients in the short term.