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Objective. Transcranial magnetic stimulation (TMS) is a clinically effective therapeutic instrument used to modulate neural activity. Despite three decades of research, two challenging issues remain, the possibility of changing the (a) stimulated spot and (b) stimulation type (real or sham) without physically moving the coil. In this study, a second-generation programmable TMS device with advanced stimulus shaping is introduced that uses a five-level cascaded H-bridge inverter and phase-shifted pulse-width modulation. The principal idea of this research is to obtain real, sham, and multi-locus stimulation using the same TMS system. Approach. We propose a two-channel modulation-based magnetic pulse generator and a novel coil arrangement, consisting of two circular coils with a physical distance of 20 mm between the coils and a control method for modifying the effective stimulus intensity, which leads to the live steerability of the target and type of stimulation. Main results. Based on the measured system performance, the stimulation profile can be steered ±20 mm along a line from the centroid of the coil locations by modifying the modulation index. Significance. The proposed system supports electronic control of the stimulation spot without physical coil movement, resulting in tunable modulation of targets, which is a crucial step towards automated TMS machines.

Quadri-pulse stimulation (QPS), a type of repetitive transcranial magnetic stimulation (rTMS), can induce a considerable aftereffect on cortical synapses. Human experiments have shown that the type of effect on synaptic efficiency (in terms of potentiation or depression) depends on the time interval between pulses. The maturation of biophysically-based models, which describe the physiological properties of plasticity mathematically, offers a beneficial framework to explore induced plasticity for new stimulation protocols. To model the QPS paradigm, a phenomenological model based on the knowledge of spike timing-dependent plasticity (STDP) mechanisms of synaptic plasticity was utilized where the cortex builds upon the platform of neuronal population modeling. Induced cortical plasticity was modeled for both conventional monophasic pulses and unidirectional pulses generated by the cTMS device, in a total of 117 different scenarios. For the conventional monophasic stimuli, the results of the predictive model broadly follow what is typically seen in human experiments. Unidirectional pulses can produce a similar range of plasticity. Additionally, changing the pulse width had a considerable effect on the plasticity (approximately 20% increase). As the width of the positive phase increases, the size of the potentiation will also increase. The proposed model can generate predictions to guide future plasticity experiments. Estimating the plasticity and optimizing the rTMS protocols might effectively improve the safety implications of TMS experiments by reducing the number of delivered pulses to participants. Finding the optimal stimulation protocol with the maximum potentiation/depression can lead to the design of a new TMS pulse generator device with targeted hardware and control algorithms.

BackgroundBrain sensing devices are approved today for Parkinson’s, essential tremor, and epilepsy therapies. Clinical decisions for implants are often influenced by the premise that patients will benefit from using sensing technology. However, artifacts, such as ECG contamination, can render such treatments unreliable. Therefore, clinicians need to understand how surgical decisions may affect artifact probability.ObjectivesInvestigate neural signal contamination with ECG activity in sensing enabled neurostimulation systems, and in particular clinical choices such as implant location that impact signal fidelity.MethodsElectric field modelling and empirical signals from 85 patients were used to investigate the relationship between implant location and ECG contamination.aResultsThe impact on neural recordings depends on the difference between ECG signal and noise floor of the electrophysiological recording. Empirically, we demonstrate that severe ECG contamination was more than 3.2x higher in left-sided subclavicular implants (48.3%), when compared to right-sided implants (15.3%). Cranial implants did not show ECG contamination.ConclusionsGiven the relative frequency of corrupted neural signals, we conclude that implant location will impact the ability of brain sensing devices to be used for “closed-loop” algorithms. Clinical adjustments such as implant location can significantly affect signal integrity and need consideration.HighlightsChronic embedded brain sensing promises algorithm-based neurostimulationAlgorithms for closed-loop stimulation can be impaired by artifactsThe relationship of implant location to cardiac dipole has relevant impact on neural signal fidelity; simple models can provide guidance on the sensitivityECG artifacts are present in up to 50% of neural signals from left subclavicular DBS systemsImplanting DBS in a right subclavicular location significantly reduces frequency of ECG artifactsCranial-mounted implants are relatively immune to artifacts

Background Brain sensing devices are approved today for Parkinson's, essential tremor, and epilepsy therapies. Clinical decisions for implants are often influenced by the premise that patients will benefit from using sensing technology. However, artifacts, such as ECG contamination, can render such treatments unreliable. Therefore, clinicians need to understand how surgical decisions may affect artifact probability. Objectives Investigate neural signal contamination with ECG activity in sensing enabled neurostimulation systems, and in particular clinical choices such as implant location that impact signal fidelity. Methods Electric field modeling and empirical signals from 85 patients were used to investigate the relationship between implant location and ECG contamination. Results The impact on neural recordings depends on the difference between ECG signal and noise floor of the electrophysiological recording. Empirically, we demonstrate that severe ECG contamination was more than 3.2x higher in left-sided subclavicular implants (48.3%), when compared to right-sided implants (15.3%). Cranial implants did not show ECG contamination. Conclusions Given the relative frequency of corrupted neural signals, we conclude that implant location will impact the ability of brain sensing devices to be used for “closed-loop” algorithms. Clinical adjustments such as implant location can significantly affect signal integrity and need consideration., Highlights • Chronic embedded brain sensing promises algorithm-based neurostimulation, but algorithms can be impaired by artifacts. • Implant location can have relevant impact on neural signal fidelity; simple models can provide guidance on the sensitivity. • ECG artifacts are present in up to 50% of neural signals from left subclavicular DBS systems. • Implanting DBS in a right subclavicular location significantly reduces frequency of ECG artifacts. • Cranial-mounted implants are relatively immune to artifacts.

OBJECTIVE: A transcranial magnetic stimulation system with programmable stimulus pulses and patterns is presented. The stimulus pulses of the implemented system expand beyond conventional damped cosine or near-rectangular pulses and approach an arbitrary waveform. METHODS: The desired stimulus waveform shape is defined as a reference signal. This signal controls the semiconductor switches of an H-bridge inverter to generate a high-power imitation of the reference. The design uses a new paradigm for TMS, applying pulse-width modulation with a non-resonant, high-frequency switching architecture to synthesize waveforms that leverages the low-pass filtering properties of neuronal cells. The modulation technique enables control of the waveform, frequency, pattern, and intensity of the stimulus. RESULTS: A system prototype was developed to demonstrate the technique. The experimental measurements demonstrate that the system is capable of generating stimuli up to 4 kHz with peak voltage and current values of ±1000 V and ±3600 A, respectively. The maximum transferred energy measured in the experimental validation was 100.4 Joules. To characterize repetitive TMS modalities, the efficiency of generating consecutive pulse triplets and quadruplets with interstimulus intervals of 1 ms was tested and verified. CONCLUSION: The implemented TMS device can generate consecutive rectangular pulses with a predetermined time interval, widths and polarities, enables the synthesis of a wide range of magnetic stimuli. SIGNIFICANCE: New waveforms promise functional advantages over the waveforms generated by current-generation TMS systems for clinical neuroscience research.

BackgroundThe nervous system functions of an animal are predominantly reflected in the behaviour and the movement, therefore the movement-related data and measuring behavior quantitatively are crucial for behavioural analyses. The animal movement is traditionally recorded, and human observers follow the animal behaviours; if they recognize a certain behaviour pattern, they will note it manually, which may suffer from observer fatigue or drift.ObjectiveAutomating behavioural observations with computer-vision algorithms are becoming essential equipment to the brain function characterization in neuroscience trials. In this study, the proposed tracking module is eligible to measure the locomotor behaviour (such as speed, distance, turning) over longer time periods that the operator is unable to precisely evaluate. For this aim, a novel animal cage is designed and implemented to track the animal movement. The frames received from the camera are analyzed by the 2D bior 3.7 Wavelet transform and SURF feature points.ResultsImplemented video tracking device can report the location, duration, speed, frequency and latency of each behavior of an animal. Validation tests were conducted on the auditory stimulation trial and the magnetic stimulation treatment of hemi-Parkinsonian rats.Conclusion/ SignificanceThe proposed toolkit can provide qualitative and quantitative data on animal behaviour in an automated fashion, and precisely summarize an animal’s movement at an arbitrary time and allows operators to analyse movement patterns without requiring to check full records for every experiment.

Background: Non-invasive magnetic stimulation therapies have become a widespread neuromodulation method utilized in the treatment of mood disorders. Although these methods have shown efficacy in the treatment of psychiatric disorders such as bipolar affective disorder and depression, a few studies have been done on Parkinson's disease (PD). Objective: This study was executed to demonstrate the effectiveness of focused transcranial magnetic stimulation (fTMS) for the treatment of PD. For this aim, a new stimulation coil design with the semi-hexagonal core was used to concentrate magnetic flux in the particular innervation nucleus. Several TMS protocols were tested to stimulate the STN region of 6-OHDA lesioned rats to determine the most effective treatment. Results: The progress of treatment was investigated by recording and analyzing the neurophysiological activity of the primary motor cortex and locomotor behaviors. After 6-OHDA injection, sharp increases in the energy and power spectral density of beta and low- gamma band were caused. Also, the motor activities of rats reduced, and the degree of catalepsy increased significantly. By completing the proposed 1Hz r-TMS treatment, the amount of energy and power density in these bands diminished and came close to the baseline. Furthermore, debilitating motor fluctuations were reverted considerably. Conclusion: Experimental results reveal that after 40 days of the non-invasive procedure, both oscillatory activity and the locomotor behavior produce remarkable changes. The 1Hz r-TMS showed acceptable performance in a reduction of symptoms in the PD. The outcomes of the animal trials have raised some hopes to employ the findings of this study in human clinical research.

Background: Growing wireless communication market is forcing the engineers to design portable and cheaper devices. This could be completed by reducing power consumption and saving battery life. Objective: In this study, a bandpass filter with a central frequency of 80 MHz with the ability to digitally tune the central frequency was designed and simulated. OTA-C blocks (gm-C) were utilized to implement the filter. For this purpose, instead of using a fixed capacitor, we use an array of voltage-variable capacitors that are placed in the form of a capacitor bank. Results: The proposed filter was implemented at the transistor level with 180 nm CMOS technology and simulated with the RF H-spice software. In the proposed filter, the bandwidth of 20 MHz was digitally tuned by 1 MHz increments. The average power consumption at the center frequency of 80 MHz was equal to 24.23 mW. Conclusion: The practical analysis of the digitally tuning filter technique and the simulation results are explained. A comparison of the performance parameters of the simulated filter with state-of-the-art filters indicates that the proposed filter can change its bandwidth over a wide range with the lower power consumption and the lower noise.

This research is executed to measure the transcranial magnetic stimulation (TMS) systems resolution. For the first time in this study, voxel resolution is proposed and exploited to evaluate TMS systems accuracy. To reach this goal novel procedure in four steps is presented. First, a small recording electrode is implanted in the targeted point of the brain, and then stimulation session is started. Induced potential in micro coil is measured and digitalized. Then the transcranial stimulation coil and test object are moved by micromanipulator and next measuring stage starts. The manipulator will sweep the 512 μl by step of 400 µm in 3-D spaces. Ultimately the measured resolution for particular stimulation coil/core is calculated. The prototype of suggested process is fabricated and tasted by in vitro and in vivo experiments. The experimental outcomes and finite element analysis results proved that the offered procedure is a powerful investigational device to measure TMS systems resolution.

In this paper, we propose a noise reduction method for a Vernier Time-to-Digital Converter (VTDC) using a first-order noise shaping structure and a gated ring oscillator (GRO). An 11bit VTDC with 4 p s effective resolution was designed and developed for a high performance All Digital Frequency Synthesizer (ADFS). The VTDC realized in 180nm CMOS, its power consumption depending on the time difference between input edges; 1 to 11mA from a 1.5 V supply.

The objective of this paper is novel circuit design and simulation for Vernier Time-to-Digital Converter (VTDC), that is using two multi-path Gated Ring Oscillator (GRO). An 11bit VTDC with 4ps effective resolution was designed and developed for a high performance All Digital Frequency Synthesizer (ADFS). The VTDC architecture combines digital standard cells accurate and arbiter circuits to make the time interval measurement, thus the VTDC is portable and scalable to other process technologies. The VTDC realized in 180nm CMOS and power consumes depending on the time difference between input edges; 1 to 11 mA from a 1.5 V supply.