Constant Current Stimulation Research Articles

Is Intraoperative Muscle Motor Evoked Potential Variability due to Fluctuating Lower Motor Neuron Background Excitability?

This pilot study tests the contribution of fluctuating lower motor neuron excitability to motor evoked potential (MEP) variability. In six pediatric patients with idiopathic scoliosis and normal neurologic examination, cascades of 30 intraoperative H-reflexes (HRs) and MEPs were evoked in the soleus muscle using constant-current stimulators and recorded through surface electrodes with a 20-second interstimulus interval. First, HRs were obtained with an intensity capable of evoking the maximum response. Subsequently, MEPs were obtained with double trains and an intensity of 700 to 900 mA. Coefficients of variation (CVs) of amplitude and area under the curve from HRs and MEPs were compared using a paired two-tailed Student t test. Coefficients of correlation between the mean CVs of HR and MEP parameters were also assessed. Pooling the results from the six patients, the mean CV of amplitude from the MEP (24.6 ± 3) was significantly higher than that from the HR (3.5 ± 4.4) (P = 0.000091). The mean CV of the MEP area under the curve (21.8 ± 4.8) was also statistically significantly higher than that from the HR area under the curve (3.4 ± 4.5) (P = 0.00091). The coefficients of correlation of the mean CV of the HR amplitude and area under the curve compared with the corresponding values of the MEP were low (r = 0.29) and very low (r = 0.03), respectively. Our results suggest that fluctuations in lower motor neuron excitability may be less important than previously thought to explain the magnitude of MEP variability. The efficacy of corticospinal volleys to recruit a larger and more stable lower motor neuron population would be critical to obtain reproducible MEPs.

Effect of different electrical stimulation systems on beef quality and palatability: Constant current compared to constant voltage

This study examined the effects of constant current electrical stimulation (CCES) compared to constant voltage electrical stimulation (CVES), when applied within the same beef carcass (n = 79), on longissimus thoracis et lumborum (LTL) quality and palatability. There was a stimulation method × time interaction for pH, with CCES reducing the 3 h post-mortem pH, but increasing the 72 h post-mortem pH compared to CVES (P < 0.001). The CCES decreased the meat subjective Japanese Meat Grading Agency (JMGA) colour scores (P < 0.05) and increased the objective L⁎ (P < 0.01), a⁎ (P < 0.05) and b⁎ (P < 0.05) colour values at 3 d post-mortem and L⁎ and b⁎ values (P < 0.05) during retail display compared to CVES, although the objective values from both stimulation methods were above established consumer acceptability thresholds. Additionally, CCES reduced the purge (P < 0.05) and drip (P < 0.01) losses, and tended to reduce shear force values (P = 0.089) compared to CVES, although these did not translate into differences in juiciness or tenderness evaluated by trained panelists (P > 0.1). Regarding flavour, the CCES meat had greater bloody/serumy flavour (P < 0.05) and corn aroma (P < 0.05), less unidentified aroma (P < 0.05), and tended to have greater corn flavour (P = 0.077) and less barnyard aroma (P = 0.079) than CVES meat. There were also increased concentrations of flavour-related volatile compounds including 2-methyl-butanal, 3-methyl-butanal and 2–5-dimethyl pyrazine levels (P < 0.05) with CCES. Overall, the CCES system slightly improved meat quality and flavour compared to CVES when applied to the same beef carcasses. Further consumer studies would be warranted to determine whether these differences translate into more acceptable meat.

Design of CMOS Analog Front-End Local-Field Potential Chopper Amplifier With Stimulation Artifact Tolerance for Real-Time Closed-Loop Deep Brain Stimulation SoC Applications.

A CMOS analog front-end (AFE) local-field potential (LFP) chopper amplifier with stimulation artifact tolerance, improved right-leg driven (RLD) circuit, and improved auxiliary path is proposed. In the proposed CMOS AFE LFP chopper amplifier, common-mode artifact voltage (CMAV) and differential-mode artifact voltage (DMAV) removal using the analog template removal method are proposed to achieve good signal linearity during stimulation. An improved auxiliary path is employed to boost the input impedance and allow the negative stimulation artifact voltage passing through. The common-mode noise is suppressed by the improved RLD circuit. The chip is implemented in 0.18- μm CMOS technology and the total chip area is 5.46-mm2. With the improved auxiliary path, the measured input impedance is larger than 133 M[Formula: see text] in the signal bandwidth and reaches 8.2 G[Formula: see text] at DC. With the improved RLD circuit, the measured CMRR is 131 - 144 dB in the signal bandwidth. Under 60-μs pulse width and 130-Hz constant current stimulation (CCS) with ±1-V CMAV and ±50-mV DMAV, the measured THD at the SC Amp output of fabricated AFE LFP chopper amplifier is 1.28%. The measurement results of In vitro agar tests have shown that with ±1.6-mA CCS pulses injecting to agar, the measured THD is 1.69%. Experimental results of both electrical and agar tests have verified that the proposed AFE LFP chopper amplifier has good stimulation artifact tolerance. The proposed CMOS AFE LFP chopper amplifier with analog template removal method is suitable for real-time closed-loop deep drain stimulation (DBS) SoC applications.

The role of lateral hypothalamic nucleus in mediating locomotive behaviors in pigeons (Columba livia)

The lateral hypothalamic nucleus (LHy) is located in the dorsolateral hypothalamus of birds, and it is essential to many life processes. However, limited information is available about the role of LHy in mediating locomotive behaviors. In this work, we investigated the structure and function of LHy in pigeons (Columba livia) by Nissl staining, immunohistochemical (IHC) staining, insituhybridization (ISH) staining and constant current stimulation methods. The results showed that LHy appears crescent in shape, and three-dimensional coordinate value range of LHy is: A: 5.0–8.0 mm, L: 0.7–1.2 mm, D: 9.5–10.3 mm. The dopaminergic neurons in LHy were distributed in small amount and concentrated manner, while the glutamatergic neurons were distributed in a large number and uniform manner. The distribution of the above two neurons at each coronal level showed a significant positive correlation (R2 = 0.7516, P < 0.001). Our work demonstrated that LHy mainly mediates forward movement (P < 0.01) and ipsilateral lateral movement (P < 0.001), and these movements were significantly effected by electrical stimulation intensity. Our results showed that LHy can mediate the generation of directional behavior and this will provide technical support for the study of locomotor behavior regulation in birds.

Research on Tremor Suppression Strategies Under a Constant Current Peripheral Electrical Stimulation Device for Parkinson's Disease.

Tremor, a prevalent symptom in Parkinson's patients, is conventionally treated with medications and craniotomy. However, the associated side effects and high surgical costs pose challenges for some individuals. In this study, a lightweight constant current electrical stimulator was developed, which is driven by the FPGA to control the underlying logic and has multiple programmable stimulation parameters. Clinical experiments involving patients with Parkinson's-related resting tremor symptoms were conducted to assess the efficacy of peripheral electrical stimulation. Two Co-contraction Avoidance Stimulation (CAS) strategies targeting nerves and muscles were proposed to reduce tremors. Four Parkinson's disease (PD) patients were recruited to verify the effectiveness of these strategies. Kinematic data recorded by inertial sensors showed that the radial nerve and muscle intervention strategies reduced the average angular velocity amplitude of finger joints during resting tremor by 75.92% and 82.41%, respectively. Notably, under low-frequency pulse stimulation (100 Hz) focused on muscle interference, a low-intensity current of no more than 8 mA maintained a tremor suppression rate of 59.91% even 5 minutes post-stimulation. Based on the experimental results, it is concluded that the constant current electrical stimulator developed in this study can effectively suppress tremor under specific stimulation strategies. These findings have significant implications for the development of lightweight, wearable tremor suppression devices. The stimulator's adaptability, coupled with its precise control parameters, demonstrates promise for advancing non-invasive and cost-effective tremor management in Parkinson's patients.

Postural Changes in Spinal Cord Stimulation Thresholds: Current and Voltage Sources

ObjectiveSpinal cord stimulation (SCS) thresholds are known to change with body position; however, these changes have not been fully characterized for both “constant-voltage” and “constant-current” pulse generators. This study aimed to evaluate and quantify changes in psychophysical thresholds resulting from postural changes that may affect both conventional paresthesia-based SCS and novel paresthesia-free SCS technologies. Materials and MethodsWe measured perceptual, usage, and discomfort thresholds in four body positions (prone, supine, sitting, standing) in 149 consecutive patients, with temporary lower thoracic percutaneous epidural electrodes placed for treating persistent low back and leg pain. We trialed 119 patients with constant-voltage stimulators and 30 patients with constant-current stimulators. ResultsMoving from supine to the sitting, standing, or prone positions caused all three thresholds (perceptual, usage, and discomfort) to increase by 22% to 34% for constant-voltage stimulators and by 44% to 82% for constant-current stimulators. Changing from a seated to a supine position caused stimulation to exceed discomfort threshold significantly more often for constant-current (87%) than for constant-voltage (63%) stimulators (p = 0.01). ConclusionsPosture-induced changes in SCS thresholds occurred consistently as patients moved from lying (supine or prone) to upright (standing or sitting) positions. These changes were more pronounced for constant-current than for constant-voltage pulse generators and more often led to stimulation-evoked discomfort. These observations are consistent with postural changes in spinal cord position measured in imaging studies, and with computer model predictions of neural recruitment for these different spinal cord positions. These observations have implications for the design, implantation, and clinical application of spinal cord stimulators, not only for conventional paresthesia-based SCS but also for paresthesia-free SCS.

Optimizing Movement Performance with Altered Sensation: An Examination of Multisensory Inputs.

Two experiments were conducted to assess the impact of induced paresthesia on movement parameters of goal-directed aiming movements to determine how visual and auditory feedback may enhance performance when somatosensory feedback is disrupted. In both experiments, neurotypical adults performed the goal-directed aiming task in four conditions: (i) paresthesia-full vision; (ii) paresthesia-no vision; (iii) no paresthesia-full vision; (iv) no paresthesia-no vision. Targets appeared on a computer screen, vision was obscured using visual occlusion spectacles, and paresthesia was induced with a constant current stimulator. The first and last 20% of trials (early and late performance) were compared to assess adaptability to altered somatosensory input. Experiment 2 added an auditory tone that confirmed successful target acquisitions. When compared to early performance in the no-paresthesia and no-vision conditions, induced paresthesia and no vision led to significantly larger endpoint error toward the body midline in both early and late performance. This finding reveals the importance of proprioceptive input for movement accuracy in the absence of visual feedback. The kinematic results indicated that vision could not fully compensate for the disrupted proprioceptive input when participants experienced induced paresthesia. However, when auditory feedback confirmed successful aiming movements in Experiment 2, participants were able to improve their endpoint variability when experiencing induced paresthesia through changes in movement preparation.

Impact of a constant current electrical stimulation (CCES) system and hormonal growth-promoting (HGP) implants on meat quality and palatability of finished steers

This study evaluated the effects of a constant current electrical stimulation (CCES) system and hormonal growth-promoting (HGP) implants on the quality and palatability of the longissimus thoracis et lumborum (LTL) from yearling-finished steers. The experiment used a total of 46 Angus cross steers, which were either non-implanted (n = 20) or implanted with trenbolone acetate and estradiol benzoate (n = 26). The CCES was applied to one side of each carcass during the slaughter process, whereas the other side remained unstimulated. Regardless of the application of HGP implants, the CCES reduced pH at 3 and 72 h post-mortem and shear force at all ageing times (P < 0.05), improved colour at 72 h post-mortem and during the retail display (P < 0.05), increased initial and overall tenderness (P < 0.01), and decreased the amount of perceived connective tissue and the proportion of trained panelists detecting spongy texture (P < 0.05) compared to meat from unstimulated carcass sides. Although CCES increased meat purge losses and reduced moisture content (P < 0.05), this did not affect meat juiciness (P > 0.10). CCES interacted with HGP to prevent increase in drip loss (P > 0.10), increase frequency of panelists detecting bloody/serumy flavour and typical texture, and reduce the proportion of panelists detecting rubbery texture in meat (P < 0.05). Regardless of stimulation treatment, meat from implanted animals had a more pronounced pH decline at 72 h post-mortem (P < 0.05) and a higher proportion of panelists finding no off-flavours (P < 0.05) or bloody/serumy flavour (P < 0.01) than non-implanted cattle. The CCES system tested in this study improved LTL quality and palatability of heavier beef carcasses.

The Exponential Attractor for Partially Dissipative Lattice System of Infinite Dimension

With the wide application of fractional differential equations, the study of dynamic systems of fractional differential equations has become one of the hotspots in the past decade. The attractor theory is one of the research directions of infinite dimensional lattice dynamical system. In paper, Eden et al. Systematically introduced the exponential attractor of deterministic autonomous dynamical system, which is a compact positive invariant set with finite fractal dimension and attracting orbits at exponential rate. The exponential attractor has a finite fractal dimension. Because of the exponential attractiveness, the exponential attractor is more stable under perturbation than the global attractor. Fitzhugh Nagumo equation is a nonlinear partial equation that describes the periodic oscillation of neuronal action potential under constant current stimulation above the threshold. For Fitzhugh Nagumo system, there are many reports on attractors, but few reports on exponential attractors. In this paper, the infinite dimensional lattice Fitzhugh Nagumo system [4] is studied. The specific contents are as follows: In part 1, the background, development and research status of FitzHugh Nagumo lattice system and the main work of this paper are introduced. In part 2, the basic concepts, inequalities and lemmas required in the research of FitzHugh Nagumo lattice system are introduced. In part 3, the initial value problem of FitzHugh Nagumo lattice system is studied. For any initial value ϕ(0), there exists a unique solution ϕ(t) of system (9) and family of mapping S(t) can generate continuous operator semigroup {S(t)} t≥0 on ,. Through lemma 3.2,3.3,3.4, it can be proved that the continuous operator semigroup {S(t)} t≥0 satisfies uniform continuity and is asymptotically compact, thus proving the existence of the exponential attractor of the system.

Advanced electrochemical potential monitoring for improved understanding of electrical neurostimulation protocols

Objective. Current-controlled neurostimulation is increasingly used in the clinical treatment of neurological disorders and widely applied in neural prostheses such as cochlear implants. Despite its importance, time-dependent potential traces of electrodes during microsecond-scale current pulses, especially with respect to a reference electrode (RE), are not precisely understood. However, this knowledge is critical to predict contributions of chemical reactions at the electrodes, and ultimately electrode stability, biocompatibility, and stimulation safety and efficacy. Approach. We assessed the electrochemistry of neurostimulation protocols in vitro with Pt microelectrodes from millisecond (classical electroanalysis) to microsecond (neurostimulation) timescales. We developed a dual-channel instrumentation amplifier to include a RE in neurostimulation setups. Uniquely, we combined potential measurements with potentiostatic prepolarization to control and investigate the surface status, which is not possible in typical stimulation setups. Main results. We thoroughly validated the instrumentation and highlighted the importance of monitoring individual electrochemical electrode potentials in different configurations of neurostimulation. We investigated electrode processes such as oxide formation and oxygen reduction by chronopotentiometry, bridging the gap between milli- and microsecond timescales. Our results demonstrate how much impact on potential traces the electrode’s initial surface state and electrochemical surface processes have, even on a microsecond scale. Significance. Our unique use of preconditioning in combination with stimulation reveals that interpreting potential traces with respect to electrode processes is misleading without rigorous control of the electrode’s surface state. Especially in vivo, where the microenvironment is unknown, simply measuring the voltage between two electrodes cannot accurately reflect the electrode’s state and processes. Potential boundaries determine charge transfer, corrosion, and alterations of the electrode/tissue interface such as pH and oxygenation, particularly in long-term in vivo use. Our findings are relevant for all use-cases of constant-current stimulation, strongly advocating for electrochemical in situ investigations in many applications like the development of new electrode materials and stimulation methods.

Sustained and potent analgesia with negligible side effects enabled by adaptive individualized granular stimulation in rat brainstem

Objectives. To clarify if an adaptive current stimulation protocol, in which current amplitude is modulated during continuous stimulation, provides better efficacy than constant current stimulation protocol with respect to analgesia caused by individualized stimulation in rat periaqueductal gray matter (PAG) /dorsal raphe nuclei (DRN). Approach. Ultrathin microelectrodes adapted for recording (n = 6) and stimulation (n = 16) were implanted in rat primary somatosensory cortex and PAG/DRN, respectively. In each animal included (n = 12), a subset of PAG/DRN microelectrodes (n = 1–3 per animal) was selected that on simultaneous stimulation blocked nociceptive withdrawal reflexes in awake unrestrained animals without noticeable side effects. Analgesic effects were subsequently assessed from both nociceptive withdrawal reflexes and intracortical pain-related responses on CO2 laser hind paw stimulation. The analgesic effects of adaptive current PAG/DRN stimulation comprising incremental increases of 5 μA/microelectrode (initial median current 30 μA/microelectrode) when effects declined were compared to the effects of constant current stimulation. Behavioral effects and brain state related changes were analyzed using quantitative movement analysis and electrocorticography (recorded on top of the dura mater), respectively. Tissue reactions and probe placement in PAG/DRN were assessed with immunohistochemistry. Main results. Powerful and sustained (4 h) analgesia was achieved with the adaptive current protocol within a rather wide area of PAG/DRN. Analgesic after-effects were seen for up to 30 min. Behavioral and brain state related side effects were minimal. Moreover, 6 weeks after implantation, there were no traces of bleedings, only small glial reactions and small but not statistically significant loss of neurons nearby indicating that the microelectrode stimulation employed is biocompatible. Significance. The results indicate that sustained and powerful analgesia with minimal side effects can be achieved by granular and individualized stimulation in PAG/DRN using an adaptive current stimulation protocol. This microelectrode technology and stimulation paradigm thus has the potential of providing a highly efficient and safe pain therapy.

Charge Injection Enhancement Comparisons of Iridium Oxide Microelectrodes In Vitro and In Vivo Using a Portable Neurostimulator.

Microelectrodes are desired to deliver more charges to neural tissues while under electrochemical safety limits. Applying anodic bias potential during neurostimulation is a known technique for charge enhancement. Here, we investigated the levels of charge enhancement with anodic bias potential in vitro and in vivo using a custom-designed portable neurostimulator. We immersed our custom microelectrode probe in saline and measured voltage transients in response to constant current stimulation with and without a 500 mV anodic bias potential. We then inserted the same microelectrode probe into the primary motor cortex of the rat brain and measured voltage transients with the same electronics. Results showed that the charge injection capacity of the activated iridium oxide microelectrode site (with 2000 μm2 geometric surface areas (GSAs)) increased by the use of the anodic bias potentials in both in vitro and in vivo: from 10 nC/phase to 32 nC/phase for 200 μs pulse widths, and from 2 nC/phase to 8 nC/phase, respectively. Thus, the order of charge injection capacities of the four cases tested in this study is as follows (from the lowest to the highest): in vivo without anodic bias, in vivo with anodic bias, in vitro without anodic bias, and in vitro with anodic bias. This work also validated in vivo use of our new portable neurostimulator which received stimulation waveforms wirelessly.

Human pain ratings to electrical sinusoids increase with cooling through a cold-induced increase in C-fibre excitability.

Low-frequency sinusoidal current applied to human skin evokes local axon reflex flare and burning pain, indicative of C-fibre activation. Because topical cooling works well as a local analgesic, we examined the effect of cooling on human pain ratings to sinusoidal and rectangular profiles of constant current stimulation. Unexpectedly, pain ratings increased upon cooling the skin from 32 to 18°C. To explore this paradoxical observation, the effects of cooling on C-fibre responses to stimulation with sinusoidal and rectangular current profiles were determined in ex vivo segments of mouse sural and pig saphenous nerve. As expected by thermodynamics, the absolute value of electrical charge required to activate C-fibre axons increased with cooling from 32°C to 20°C, irrespective of the stimulus profile used. However, for sinusoidal stimulus profiles, cooling enabled a more effective integration of low-intensity currents over tens of milliseconds resulting in a delayed initiation of action potentials. Our findings indicate that the paradoxical cooling-induced enhancement of electrically evoked pain in people can be explained by an enhancement of C-fibre responsiveness to slow depolarization at lower temperatures. This property may contribute to symptoms of enhanced cold sensitivity, especially cold allodynia, associated with many forms of neuropathic pain.

Paced breathing and respiratory movement responses evoked by bidirectional constant current stimulation in anesthetized rabbits.

Objective: Diaphragm pacing (DP) is a long-term and effective respiratory assist therapy for patients with central alveolar hypoventilation and high cervical spinal cord injury. The existing DP system has some limitations, especially high price, inconvenience preoperative evaluation methods and diaphragm fatigue easily. Our objective was to develop a DP system and evaluated reliability through hardware testing and animal experiments. Methods: A DP system with bidirectional constant current was designed, manufactured and tested. Effects of a wide range of stimulus amplitudes (range: .5-2.5mA) and frequencies (range: 10-250Hz) on airflow and corresponding inspired volume were investigated during DP. Differences in airflow characteristics under various stimulation parameters were evaluated using power function. ECG interference in diaphragm electromyography (EMGdi) was filtered out using stationary wavelet transform to obtain pure EMGdi (EMGdip). 80-min period with a tendency for diaphragm fatigue by root mean square (RMS) and centroid frequency (f c ) of EMGdip was studied. Results: The increase of stimulus frequency and amplitude in animals resulted in different degrees of increase in envoked volume. Significant difference in Airflow Index (b) between anesthesia and DP provided a simple, non-invasive and feasible solution for phrenic nerve conduction function test. Increased stimulation duration with the developed DP system caused less diaphragm fatigue. Conclusion: A modular, inexpensive and reliable DP was successfully developed. Its effectiveness was confirmed in animal experiments. Significance: This study is useful for design of future implantable diaphragmatic pacemakers for improving diaphragm fatigue and convenient assessment of respiratory activity in experiments.

Clinical Practice Guidelines for the Use of Transcranial Direct Current Stimulation in Psychiatry.

Clinical Practice Guidelines for the Use of Transcranial Direct Current Stimulation in Psychiatry.

Constant current or constant voltage deep brain stimulation: short answers to a long story.

Recently, the feature of generating constant current output has been added to the implantable pulse generators (IPGs). The efficacy of the conventionally used constant voltage (CV) stimulation has been proved in different movement and psychiatric disorders. In this systematic review, we aimed to discuss the effect of constant current (CC) and constant voltage stimulation on patients with Parkinson's disease (PD) who had subthalamic nucleus deep brain stimulation implantation; we also compared these methods of stimulation with each other. Using the words "Deep brain stimulation", "constant current" and "constant voltage", we developed a broad search strategy and a systematic search was conducted in PubMed, Scopus, Web of Science and Cochrane electronic bibliographic databases. Studies on the Parkinson's disease patients with subthalamic deep brain stimulation, which mentioned constant current or/and constant voltage setting stimulation were included. After screening of 284 articles, 10 reports were found eligible for this study. The score of unified Parkinson's disease rating scale part 3 was improved compared to the baseline, whether the stimulation was CV at baseline or CC. No significant change in non-motor outcomes was found. Although CC stimulation has shown a significant improvement in both motor and non-motor symptoms of PD, switching from CV to CC did not result in a significant change in the score of these items based on UPDRS. To sum up, implantation of constant current devices is safe and significantly improves motor function; it also maintains an acceptable safety profile in patients with PD.

Physically constrained neural networks for inferring physiological system models.

Systems biology and systems neurophysiology in particular have recently emerged as powerful tools for a number of key applications in the biomedical sciences. Nevertheless, such models are often based on complex combinations of multiscale (and possibly multiphysics) strategies that require ad hoc computational strategies and pose extremely high computational demands. Recent developments in the field of deep neural networks have demonstrated the possibility of formulating nonlinear, universal approximators to estimate solutions to highly nonlinear and complex problems with significant speed and accuracy advantages in comparison with traditional models. After synthetic data validation, we use so-called physically constrained neural networks (PINN) to simultaneously solve the biologically plausible Hodgkin-Huxley model and infer its parameters and hidden time-courses from real data under both variable and constant current stimulation, demonstrating extremely low variability across spikes and faithful signal reconstruction. The parameter ranges we obtain are also compatible with prior knowledge. We demonstrate that detailed biological knowledge can be provided to a neural network, making it able to fit complex dynamics over both simulated and real data.

A Highly Miniaturized, Chronically Implanted ASIC for Electrical Nerve Stimulation.

We present a wireless, fully implantable device for electrical stimulation of peripheral nerves consisting of a powering coil, a tuning network, a Zener diode, selectable stimulation parameters, and a stimulator IC, all encapsulated in biocompatible silicone. A wireless RF signal at 13.56 MHz powers the implant through the on-chip rectifier. The ASIC, designed in TSMC's 180 nm MS RF G process, occupies an area of less than 1.2 mm2. The IC enables externally selectable current-controlled stimulation through an on-chip read-only memory with a wide range of 32 stimulation parameters (90-750 µA amplitude, 100 µs or 1 ms pulse width, 15 or 50 Hz frequency). The IC generates the constant current waveform using an 8-bit binary weighted DAC and an H-Bridge. At the most power-hungry stimulation parameter, the average power consumption during a stimulus pulse is 2.6 mW with a power transfer efficiency of ∼5.2%. In addition to benchtop and acute testing, we chronically implanted two versions of the device (a design with leads and a leadless design) on two rats' sciatic nerves to verify the long-term efficacy of the IC and the full system. The leadless device had the following dimensions: height of 0.45 cm, major axis of 1.85 cm, and minor axis of 1.34 cm, with similar dimensions for the device with leads. Both devices were implanted and worked for experiments lasting from 21-90 days. To the best of our knowledge, the fabricated IC is the smallest constant-current stimulator that has been tested chronically.

The role of posterior pallial amygdala in mediating motor behaviors in pigeons

The posterior pallial amygdala (PoA) is located on the basolateral caudal telencephalon, including the basal division of PoA (PoAb) and the compact division of PoA (PoAc). PoA plays a vital role in emotion regulation and is considered a part of the amygdala in birds. However, the regulatory functions responsible for motor behaviors and emotions between PoAb and PoAc are poorly understood. Therefore, we studied the structure and function of PoA by tract-tracing methods, constant current electrical stimulation, and different dopamine receptor drug injections in pigeons (Columba livia domestica). PoAb connects reciprocally with two nuclear groups in the cerebrum: 1) a continuum comprising the temporo–parieto–occipitalis, corticoidea dorsolateralis, hippocampus, and parahippocampalis areas and 2) rostral areas of the hemisphere, including the nucleus septalis lateralis and nucleus taeniae amygdalae. Extratelencephalic projections of PoAb terminate in the lateral hypothalamic nucleus and are scattered in many limbic midbrain regions. PoAb and PoAc mainly mediated the turning movement. In the ‘open-field’ test, D1 agonist and D2 antagonist could significantly reduce the latency period for entering into the central area and increase the residence time in the central area, whereas D1 antagonist and D2 agonist had the opposite effect. PoAb and PoAc are important brain areas that mediate turning behavior.

Design and Ex Vivo Experimental Validations of the CMOS 256-Pixel Photovoltaic-Powered Subretinal Prosthetic Chip With Auto-Adaptive Pixels for a Wide Image Illuminance Range.

To design and verify a CMOS 256-pixel photovoltaic-powered subretinal prosthetic chip with key advances over the state-of-the-art. The three key advances are: 1) automatic adaptation to changing background illuminance levels; 2) increase of injection charges with reduced crosstalk leakage charges, enhanced charge balance, and low process variations; 3) stable stimulation voltage to keep the safety of water window. The novel auto-adaptive pixel circuit is designed to realize the Michealis - Menten equation (MME) so that the automatic adaptation to changing background illuminance can be achieved. Both improved biphasic constant current stimulator (CCS) via bi-directional shared electrodes (BDSEs) with optimized stimulation pattern and improved constant current generator/ring oscillator are designed to achieve the above second advance on injection charges. The closed-loop charge pump is designed to achieve the third advance. The measured dynamic range of image illuminance is increased to 54.7 dB. The maximum stimulation charge is 8.89nC. The measured stimulation current mismatch is 1.7% and the measured residual charge is 0.150 nC. The measured variations of stimulation frequencies are from 26 Hz to 29.7 Hz. The results of ex vivo tests have shown that the proposed subretinal chip can evoke spiking responses of RGCs. The function of adaptation process to background illuminance has also been verified. Through both electrical measurement and ex vivo tests, the functions of designed subretinal chip have been validated successfully. It is shown that the proposed subretinal chip is a promising solution for subretinal prostheses.