Conventional spinal cord stimulation (SCS) delivers a fixed-input of energy into the dorsal column. A new SCS approach exists in controlling stimulation dose by measuring the recruitment of fibers in the dorsal column and by using the amplitude of the evoked compound action potentials (eCAPs) to maintain stimulation within an individualized therapeutic range. As a reminder, eCAP represents a synchronized response generated by a group of electrically activated nerve fibers to stimuli.
A key challenge in the measurement of evoked compound action potentials (eCAP) is the signal amplitude being very low. Spinal cord potential can be in the range of ten micro volts and a high precision (about one microvolt) measurement technique will be required to extract the eCAP. Further, if the initial stimulation potential is in volts, then stimulus artifacts would likely impact the evoked response unless the stimuli and measurement electrodes are spatially separated to minimize this artifact contamination.
Despite physical separation of stimuli from evoked signal measurement points, electrical circuit design techniques have critical impact on the measurement accuracy. Ideally a very high dynamic range circuit is desired to detect a very low signal from a high-amplitude stimulus but this is not practical.
Fortunately, there are several techniques in ultra-low noise amplifier design.
One may prefer to use an operational amplifier (Op Amp) or an instrumentation amplifier based design for simplicity, but a transistor-based discrete amplifier can have much lower noise, with a similar power consumption. Whether Op Amp or transistor based, noise of an amplifier can be reduced by paralleling amplifiers. This would lower noise by the square root of the number of parallel stages. A transistor-based design helps further, especially if JFET parts are used, since this would increase the input impedance.
It should be emphasized here that the resistor value selection is critical in low noise amplifier design, since a resistor contributes to circuit noise by about 4nV/rt Hz (nano volt per root hertz) for each 1 k ohms. In addition to its own noise contribution, resistor values also affect noise due to input noise current of amplifiers.
Each noise value Including the contribution of amplifier input noise voltage (multiplied by amplifier gain), amplifier output noise voltage, total circuit noise will add up as 'root of sums of squares of each contributor' and these can easily add up to hundreds of micro volts rms (root mean square) when calculated for the operating bandwidth of the circuit.
A low noise circuit designer should also be aware of the Gaussian distribution of random noise with the probability of +/- 3 sigma (6 sigma distribution). This implies 99.7% of total noise (in either plus and minus amplitude direction). This peak-to-peak noise will reach 6 times the rms value and can significantly shadow the low level evoked nerve signals being measured.
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The results of a multicenter, double-blind, crossover, randomized controlled trial (RCT) that investigated the effects of rate of stimulation on analgesia in kilohertz frequency (1–10 kHz) spinal cord stimulation (SCS) suggests that patients experienced EQUIVALENT PAIN RELIEF as measured by (e-diary numeric rating scale) ED-NRS (p ≤ 0.002). For details, please see the source.
Patients were implanted with SCS systems and underwent an eight-week search to identify the best location (“sweet spot”) of stimulation at 10 kHz within the searched region (T8–T11). Patients who responded to 10 kHz per ED-NRS pain scores proceeded to double-blind rate randomization. Patients received 1, 4, 7, and 10 kHz SCS at the same sweet spot found for 10 kHz in randomized order (four weeks at each frequency). For each frequency, pulse width and amplitude were titrated to optimize therapy.
All frequencies provided equivalent pain relief, while 1 kHz requiring 60–70% less charge than higher frequencies (p ≤ 0.0002).
One important question is about the sensitivity of analgesia to frequencies outside the range of 1–10 kHz., both below and above.
Benefit of lower frequency would be even lesser charge for higher battery longevity and equivalent pain relief without paresthesia. Lower frequencies for SCS may be effective in the sub-perception modality (although, whether the mechanisms of action underlying burst SCS and kilohertz frequency SCS are the same is an open question). Other questions include whether the mechanisms of action for these two broad modalities of SCS (paresthesia and sub-perception) overlap in frequency range, and whether they can be engaged simultaneously to potentially yield an additive effect that further improves therapy.
The bottom line is: As fundamental understanding of mechanisms of action increases, continued optimization is likely and awaiting researchers.
A full-featured, fully programmable, pulse-generator platform such as Lone Star Neuro's 'indication agnostic platform' may be an ideal tool to empower institutions immediately to further medical research, since the platform can be set to deliver constant current or constant voltage pulses with programmable amplitude and pulse-width, at any frequency from 1 Hz to well above 40 (forty) kHz with simple C-code programming.
The heterogeneous and conductive nature of biological tissue render near-field inductive coupling ineffective in powering devices if implanted deeply. Similar to Lone Star Neuro's pulse-generator platform, SCMR (Strongly Coupled Magnetic Resonance) could overcome this limitation. If further device miniaturization is required, such as a device with dual electrodes and no batteries, mid-field power transfer can now be an option:
Power transfer in the mid-field region can (around a wavelength away from the source) transfer enough power to a millimeter scale implant deep inside a tissue. Further, mid-field region allows power flow lines to be manipulated with an interference pattern for focusing them in a specific spot, and well within the SAR (Specific Absorption Rate) safety limits.
Ho et al explain the theory behind mid-field power transfer, which is straightforward. Design and implementation of a mid-field power transmitter and a miniaturized receiver is also well within the capabilities of today's semiconductor components and manufacturing technologies, promising new millimeter-scale medical implants for a variety of therapy modalities which have not been feasible until recently.