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- All Subjects: Neuromodulation
- All Subjects: Bioengineering
- Creators: Buneo, Christopher
Neuromodulation is an emerging field of research that has a proven therapeutic benefit on a number of neurological disorders, including epilepsy and stroke. It is characterized by using exogenous stimulation to modify neural activity. Prior studies have shown the positive effect of non-invasive trigeminal nerve stimulation (TNS) on motor learning. However, few studies have explored the effect of this specific neuromodulatory method on the underlying physiological processes, including heart rate variability (HRV), facial skin temperatures, skin conductance level, and respiratory rate. Here we present preliminary results of the effects of 3kHz supraorbital TNS on HRV using non-linear (Poincaré plot descriptors) and time-domain (SDNN) measures of analysis. Twenty-one (21) healthy adult subjects were randomly assigned to 2 groups: 3kHz Active stimulation (n=11) and Sham (n=10). Participants’ physiological markers were monitored continuously across three blocks: one ten-minute baseline block, one twenty-minute treatment block, and one ten-minute recovery block. TNS targeting the ophthalmic branches of the trigeminal nerve was delivered during the treatment block for twenty minutes in 30 sec. ON/OFF cycles. The active stimulation group exhibited larger values of all Poincaré descriptors and SDNN during blocks two and three, signifying increased HRV and autonomic nervous system activity.
In this experiment Positive Affect and Negative Affect Schedule (PANAS) scores are recorded daily to monitor mood differences between pre and post treatment (TENS vs Sham). PANAS scores were found to be insignificant between groups. Pittsburgh Sleep Quality Index (PSQI), and Fitbit were chosen to study perceived sleep, and objective sleep. Both PSQI, and Fitbit found insignificant differences between TENS and Sham. Finally, the Beck Depression and Beck Anxiety Inventories were administered weekly to determine if there are immediate changes to depressive and anxiety symptom, after a week of treatment (TENS vs Sham). A significant difference was found between the pre and post of the TENS treatment group. The TENS group was not found to be significantly different from Sham, potentially the result of a placebo effect. These results were found with n=10 participants in the TENS treatment group and n=6 in the sham group.
Recordings from both layers of the flexible μECoG array showed frequency features typical of cortical local field potentials (LFP) and were shown to be stable in amplitude over time. Recordings from both layers also showed consistent, frequency-dependent modulation after induction of general anesthesia, with large increases in beta and gamma band and decreases in theta band observed over three experiments. Recordings from conventional μECoG arrays over human cortex showed robust modulation in a high frequency (250-2000 Hz) band upon production of spoken words. Modulation in this band was used to predict spoken words with over 90% accuracy. Basal Ganglia neuronal AP firing was also shown to significantly correlate with various cortical μECoG recordings in this frequency band. Results indicate that μECoG surface electrodes may detect high frequency neuronal activity potentially associated with AP firing, a source of information previously unutilized by these devices.
The scale at which non-penetrating electrode arrays can interface with cortex is evaluated in the context of extracting useful information. Articulate movements were decoded from surface microelectrode electrodes, and additional spatial analysis revealed unique signal content despite dense electrode spacing. With a basis for data extraction established, the focus shifts towards the information encoding half of neural interfaces. Finite element modeling was used to compare tissue recruitment under surface stimulation across electrode scales. Results indicated charge density-based metrics provide a reasonable approximation for current levels required to evoke a visual sensation and showed tissue recruitment increases exponentially with electrode diameter. Micro-scale electrodes (0.1 – 0.3 mm diameter) could sufficiently activate layers II/III in a model tuned to striate cortex while maintaining focal radii of activated tissue.
In vivo testing proceeded in a nonhuman primate model. Stimulation consistently evoked visual percepts at safe current thresholds. Tracking perception thresholds across one year reflected stable values within minimal fluctuation. Modulating waveform parameters was found useful in reducing charge requirements to evoke perception. Pulse frequency and phase asymmetry were each used to reduce thresholds, improve charge efficiency, lower charge per phase – charge density metrics associated with tissue damage. No impairments to photic perception were observed during the course of the study, suggesting limited tissue damage from array implantation or electrically induced neurotoxicity. The subject consistently identified stimulation on closely spaced electrodes (2 mm center-to-center) as separate percepts, indicating sub-visual degree discrete resolution may be feasible with this platform. Although continued testing is necessary, preliminary results supports epicortical microelectrode arrays as a stable platform for interfacing with neural tissue and a viable option for bi-directional BCI applications.