Concurrent Stimulation Research Articles

Organic Synaptic Transistors and Printed Circuit Board Defect Inspection with Photonic Stimulation: A Novel Approach Using Oblique Angle Deposition.

This study introduces a photonic stimulation-based synaptic transistor utilizing oblique angle deposition (OAD) of dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]thiophene (DNTT). While OAD enables advanced nanostructures, its application to organic materials remains largely unexplored. Here, the electrical characteristics and photoinduced trap behavior of obliquely deposited DNTT transistors are systematically investigated, successfully replicating key synaptic functions. OAD-controlled grain size and spacing in the DNTT channel yield distinct performance metrics compared to conventional devices. The introduced trap regions enable stable synaptic behavior across diverse gate voltage (VG) conditions. By adjusting presynaptic photonic pulse intensity, duration, and repetition, a robust transition is achieved to long-term memory (LTM). The device further demonstrates reliable optoelectronic synaptic operation over 52 durability cycles. Concurrent photonic stimulation enables parallel potentiation-depression dynamics, enhancing processing speed and performance, highlighting its promise for next-generation neuromorphic computing. Its application is also showed in printed circuit board (PCB) defect inspection, successfully mimicking biological synapses under simultaneous photonic stimulation.

Multi-coil TMS for preclinical applications in ultra-high-field MRI

Abstract Monitoring cortical responses to neuromodulation on preclinical models can elucidate fundamental mechanisms of brain function. Concurrent brain stimulation and imaging is challenging, usually compromising spatiotemporal resolution, accuracy, and versatility. Here, we report on a non-invasive brain stimulation system with electronic control of neuromodulation parameters in a 9.4-T magnetic resonance imaging (MRI) environment. In the imaging scanner, multi-coil transcranial magnetic stimulation (mTMS) is delivered with a 2-coil array, and the MRI signal is measured with a radiofrequency coil. The mTMS can change the stimulus orientation with 1° resolution in a millisecond. Without physically rotating the coils, we evoked orientation-specific muscle responses after cortical stimulation on an anesthetized rat. The mTMS system was successfully implemented and tested with the small-animal MRI, showing minimal interference with B0 and B1+ fields and uncompromised image quality. A delay of 40 ms between the stimulation pulse and fMRI acquisition—similar or even shorter than those previously described in humans—led to artifact-free images. Concurrent electronically targeted brain stimulation and neuroimaging provides a valuable tool for exploring whole-brain network functions, endorsing more efficient treatment protocols.

Electrical stimulation of the dorsolateral prefrontal cortex inhibits vestibular signalling in humans: A BOLD fMRI study.

Electrical stimulation of the dorsolateral prefrontal cortex inhibits vestibular signalling in humans: A BOLD fMRI study.

Age-specific neural responses to SMA and M1 stimulation during implicit motor sequence learning: Insights from a concurrent tDCS-fNIRS approach.

Age-specific neural responses to SMA and M1 stimulation during implicit motor sequence learning: Insights from a concurrent tDCS-fNIRS approach.

Assessing Neuromodulation Effects of Theta Burst Stimulation to the Prefrontal Cortex Using Transcranial Magnetic Stimulation Electroencephalography (TMS-EEG).

Theta burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (TMS), is capable of non-invasively modulating cortical excitability. TBS is gaining popularity as a therapeutic tool for psychiatric disorders such as depression, in which the dorsolateral prefrontal cortex (DLPFC) is the main therapeutic target. However, the neuromodulatory effects of TBS on prefrontal regions remain unclear. Concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) can assess neuromodulation in non-motor regions using TMS-evoked potentials (TEPs) and event-related synchronisation/desynchronisation (ERS/D). We assessed 24 healthy participants (13 males, mean age 25.2 ± 9.9 years) in a single-blinded crossover study design, following intermittent TBS, continuous TBS and sham applied to the left DLPFC. TEPs and ERS/D were obtained at baseline and 2-, 15- and 30-min post-stimulation. Four TEP components (N40, P60, N100 and P200) and two frequency bands (theta and gamma) were analysed using mixed effects repeated measures models (MRMM). Results indicated no significant effects for any assessed components or frequency bands. Relative to sham, the largest TEP effect size was obtained for the N100 component at 15 min post-iTBS (d = -0.50), and the largest frequency effect was obtained for gamma ERS at 15 min post-cTBS (d = 0.53). These results were in the same direction but smaller than found in previous studies, suggesting that effect sizes of the neuromodulatory effects of TBS may be lower than previously reported.

Concurrent Non-Invasive Brain Stimulation and Behavioral Activation Psychotherapy Increases Goal-Directed Behavior in MDD: A Double-Blind Placebo-Controlled Randomized Pilot Clinical Trial

Concurrent Non-Invasive Brain Stimulation and Behavioral Activation Psychotherapy Increases Goal-Directed Behavior in MDD: A Double-Blind Placebo-Controlled Randomized Pilot Clinical Trial

Repeated tDCS at clinically-relevant field intensity can boost concurrent motor learning in rats.

Electric fields used in clinical trials with transcranial direct current stimulation (tDCS) are small, with magnitudes that have yet to demonstrate measurable effects in preclinical animal models. We hypothesized that weak stimulation will nevertheless produce sizable effects, provided that it is applied concurrently with behavioral training, and repeated over multiple sessions. We tested this here in a rodent model of dexterous motor-skill learning. We developed a preparation that allows concurrent stimulation during the performance of a pellet-reaching task in freely behaving rats. The task was automated to minimize experimenter bias. We measured field magnitudes intracranially to calibrate the stimulation current. In this study, only male rats were used. Animals were trained for 20 min with concurrent epicranial tDCS over 10 daily sessions. Behavior was recorded with high-speed video to quantify reaching dynamics. We also measured motor-evoked potentials (MEPs) bilaterally with epidural microstimulation. The new electrode montage enabled stable stimulation over 10 sessions with a field intensity of 2V/m at the motor cortex. The number of successful reaches improved across days of training, and the rate of learning was higher in the anodal group as compared to sham-control animals (F(1)=7.12, p=0.008, N=24). MEPs were not systematically affected by tDCS. Post hoc analysis suggests that tDCS modulated motor learning only for right-pawed animals, improving success of reaching, but limiting stereotypy in these animals. Repeated and concurrent anodal tDCS can boost motor-skill learning at clinically-relevant field intensities. In this animal model the effect interacted with paw preference and was not associated with corticospinal excitability.Significance Statement The effects of tDCS have been explored in numerous human clinical trials, but the mechanisms of action of weak electric fields remain unclear. In vitro studies show that constant electric fields at 2.5 V/m can enhance the efficacy of synapses undergoing plasticity. This study demonstrates in a rodent model that tDCS of only 2 Vm when applied concurrently to behavioral training can improve motor skill learning, and reduce stereotypy of reaching behavior. These effects accumulated over 10 days of training. Motor evoked potentials (MEP), which are often used to demonstrate plastic effects in humans on a time scale of hours, were not measurably affected by tDCS on this longer time scale.

The Supplementary Motor Area as a Flexible Hub Mediating Behavioral and Neuroplastic Changes in Motor Sequence Learning: A TMS and TMS-EEG Study.

Attempts have been made to modulate motor sequence learning (MSL) through repetitive transcranial magnetic stimulation, targeting different sites within the sensorimotor network. However, the target with the optimum modulatory effect on neural plasticity associated with MSL remains unclarified. This study was therefore designed to compare the role of the left primary motor cortex and the left supplementary motor area proper (SMAp) in modulating MSL across different complexity levels and for both hands, as well as the associated neuroplasticity by applying intermittent theta burst stimulation together with the electroencephalogram and concurrent transcranial magnetic stimulation. Our data demonstrated the role of SMAp stimulation in modulating neural communication to support MSL, which is achieved by facilitating regional activation and orchestrating neural coupling across distributed brain regions, particularly in interhemispheric connections. These findings may have important clinical implications, particularly for motor rehabilitation in populations such as post-stroke patients.

Catalytic Degradation of Organic Dyes Indicates Anti-Proliferative Effects of Magnetoelectric Nanoparticles

Abstract Over the past decade, magnetoelectric nanoparticles (MENPs) have proven effective in generating local electric fields in response to stimulation with a magnetic field. The applications of such nanoparticles are many and varied, with examples of prior research including use for on-demand drug release, wireless modulation and recording of neural activity, and organic dye degradation. This study investigates the potential for organic dye degradation to be used as a rapid and efficient screening tool to detect the magnetoelectric effect of MENPs, and how the results of such a test mirror the antiproliferative effect of said nanoparticles. Trypan blue was selected as an azo dye to test for dye degradation. Vials of the dye were treated with CoFe2O4@BaTiO3 core-shell MENPs of varying characteristics, both with and without concurrent 1-kHz 250-Oe magnetic stimulation. Dye degradation was measured using ultraviolet (UV)-vis spectroscopy. Dye degradation efficacy varied with varying nanoparticle synthesis parameters. As controls, nanoparticles of the same composition, but with an insignificant magnetoelectric effect, were used. SKOV-3 ovarian cancer cells were then treated with the same nanoparticles, and viability was measured with an adenosine triphosphate (ATP) assay. These measurements show a decrease in cell viability up to 60.3% of control (p = 0.0052), which mirrored the efficacy of dye degradation of up to 69.8% (p = 0.0037) in each of the particle variants, demonstrating the value of azo dye degradation as a simple screening test for MENPs, and showing the potential of MENPs used as wirelessly controlled nanodevices to allow targeted electric field-based treatments.

SEX DIFFERENCES IN BRAIN EXCITABILITY REVEALED BY CONCURRENT ITBS/FNIRS

Abstract Background Repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (lDLPFC) is a demonstrably efficacious therapy for various symptoms of psychiatric disorders (Kan et al., 2023b). Recent evidence indicates sex differences is an imperative factor in optimizing pharmacotherapeutic antidepressant treatments (Wilson et al., 2023). However, sex differences in rTMS over lDLPFC and the underlying neural mechanisms remain unclear. Aims & Objectives Here, we investigated whether the real-time neural response to intermittent theta- burst stimulation (iTBS) differs between men and women, and which mechanisms may mediate these differences. Methods In a series of experiments, we investigated potential sex differences in healthy, right-handed participants. We measured prefrontal hemoglobin concentrations during rest, during cognitive tasks (N- back and verbal fluency), as well as during concurrent brain stimulation with iTBS using functional near- infrared spectroscopy (fNIRS). We capitalized on a concurrent iTBS/fNIRS setup developed in our lab that allows measuring the instantaneous neuronal response of iTBS over lDLPFC (Kan et al., 2023a). A figure- of-eight shaped cooling coil (Cool-B65) and the MagPro magnetic stimulator (MagVenture) were used for stimulation Results We found (1) a biological sex difference in absolute hemoglobin concentrations in the left DLPFC (p<0.001, n=66, 38 females); (2) that this sex difference is amplified by iTBS (p=0.001, n=56, 23 females) but not by cognitive tasks (both p>=0.05, n=71, 46 females); and (3) that the sex difference amplified by iTBS is modulated by stimulation intensity (p=0.004, n=24, 12 females, see Figure 1). Discussion & Conclusion Our results indicate that sex-specific effects of stimulation-induced prefrontal excitability are an important aspect to consider in the advancement of brain stimulation protocols towards precision psychiatry (Mauvais-Jarvis et al., 2020). References KAN, R. L. D., LIN, T. T. Z., ZHANG, B. B. B., GIRON, C. G., JIN, M., QIN, P. P. I., XIA, A. W. L., CHAN, S. K. W., CHAU, B. K. H. &KRANZ, G. S. 2023a. Moderators of stimulation-induced neural excitability in the left DLPFC: A concurrent iTBS/fNIRS case study. Brain Stimul. KAN, R. L. D., PADBERG, F., GIRON, C. G., LIN, T. T. Z., ZHANG, B. B. B., BRUNONI, A. R. &KRANZ, G. S. 2023b. Effects of repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex on symptom domains in neuropsychiatric disorders: a systematic review and cross-diagnostic meta- analysis. Lancet Psychiatry, 10, 252-259. MAUVAIS-JARVIS, F., BAIREY MERZ, N., BARNES, P. J., BRINTON, R. D., CARRERO, J. J., DEMEO, D. L., DE VRIES, G. J., EPPERSON, C. N., GOVINDAN, R., KLEIN, S. L., LONARDO, A., MAKI, P. M., MCCULLOUGH, L. D., REGITZ-ZAGROSEK, V., REGENSTEINER, J. G., RUBIN, J. B., SANDBERG, K. &SUZUKI, A. 2020. Sex and gender: modifiers of health, disease, and medicine. Lancet, 396, 565-582. WILSON, J. D., GERLACH, A. R., KARIM, H. T., AIZENSTEIN, H. J. &ANDREESCU, C. 2023. Sex matters: acute functional connectivity changes as markers of remission in late-life depression differ by sex. Mol Psychiatry.

Enhancing prefrontal modulation by phase-locking intermittent theta burst stimulation to a concurrent transcranial alternating current stimulation

Abstract Theta burst stimulation (TBS) modulates cortical excitability by applying bursts of transcranial magnetic stimulation (TMS) in theta rhythms. Individual responses to TBS vary however greatly due to various factors, such as anatomical differences or the phase of the ongoing oscillatory activity in which TBS pulses are applied. To combat this variability, we exploit the ability of transcranial alternating current stimulation (tACS) to shape the state of cortical excitability in a phase-dependent manner. While cortical excitability is increased at crests of the tACS-induced current, applying the TBS triplet pulses at these crests has the potential to produce larger neuronal responses and thus increase the likelihood of long-term potentiation (LTP). In our randomized sham-controlled study, we focused on enhancing prefrontal cortex excitability by phase-locking intermittent TBS (iTBS) to the crests of an induced 5 Hz tACS current. Twenty-seven healthy participants received two iTBS sessions, once paired with sham-tACS and once with active tACS in a cross-over design. We evaluated effects of our stimulation protocol on cortical excitability by comparing TMS-induced activity and resting-state Microstates in the EEG before and after the stimulation as well as between the two sessions. We found significant effects of iTBS on channel-wise, global, and oscillatory TMS-induced activity, as well as changes in Microstates. The concurrent, phase-locked tACS-iTBS protocol notably decreased the N100 amplitude of the Global Mean Field Power. We also found that baseline TMS-induced oscillatory activity was a key predictor of changes in TMS-related oscillatory activity. In the case of TMS-related gamma oscillations, a significant interaction between our stimulation protocols and baseline activity was observed, indicating that the relationship between baseline and post-iTBS oscillations was strengthened by the concurrent phase-locked tACS-iTBS stimulation protocol. These findings highlight the potential of phase-locked tACS to enhance the effects of iTBS on prefrontal cortical excitability.

Stochastic Signal Processing Based Stimulation Artifact Cancellation in ΔΣ Neural Frontend.

This paper presents a neural recorder frontend featuring electrical stimulation artifact cancellation by employing an adaptive LMS filter in the stochastic domain. The recording system comprises of a low-noise analog frontend and a 1st-order ΔΣ modulator. A power-efficient stochastic signal processor, occupying an area of 0.12 mm2, processes the ΔΣ modulator output bitstream to learn and compensate for artifacts induced by concurrent electrical stimulation. The proposed approach, validated on a prototype ASIC fabricated in 180 nm CMOS technology, has a total power consumption of 6.83 μW, with the stochastic signal processor consuming only 0.51 μW. Experimental results demonstrate that the system effectively suppresses peak-to-peak stimulation artifacts of 200 mV by approximately 33 dB over a 10 kHz bandwidth, establishing it as a novel state-of-the-art real-time artifact cancellation system. Furthermore, in-vitro validation for both biphasic and monophasic stimulation confirms its efficacy, with 74.3 mVpp artifacts from biphasic stimulation being attenuated by 25 dB.

An Active Microchannel Neural Interface for Implantable Electrical Stimulation and Recording.

A mm-sized, implantable neural interface for bidirectional control of the peripheral nerves with microchannel electrodes is presented in this paper. The application-specific integrated circuit (ASIC) developed in a 0.18 μm CMOS technology is designed to achieve highly selective, concurrent control of 300-μm-wide groups of small nerve sections. It has in-situ, high-voltage-compliant (45 V) electrical stimulation and low-voltage (1.8 V) neural recording in each channel. Biphasic stimulus current pulses up to 124 μA with a 2 μA resolution are generated between 7.4 Hz and 20 kHz frequencies to stimulate and block neural activity. Action potentials are measured across a 10 kHz bandwidth with a variable gain response that ranges up to 72 dB. The neural recording front-end implements a low-power and low-noise biopotential amplifier with an input-referred noise (IRN) of 2.74 μVrms across the full measurement bandwidth. Automatic detection and reduction of stimulus artifacts is realised using a pole-shifting mechanism with a 1-ms amplifier recovery time. Versatile control of concurrently-operating channels is achieved in a two-channel, 2.31 mm2 interface ASIC using local control that allows up to seven devices to operate in parallel. Invitro validation of the active interface shows feasibility for closed-loop peripheral nerve control, while ex-vivo analyses of concurrent stimulation and recording demonstrates the measured neural response to electrical stimuli.

The BCM1-EGY1 module balances chlorophyll biosynthesis and breakdown to confer chlorophyll homeostasis in land plants

The BCM1-EGY1 module balances chlorophyll biosynthesis and breakdown to confer chlorophyll homeostasis in land plants

Acceptability, Feasibility, and Effectiveness of Concurrent High-Definition Transcranial Direct Current Stimulation and Cue Exposure in Cannabis Use Disorder

Acceptability, Feasibility, and Effectiveness of Concurrent High-Definition Transcranial Direct Current Stimulation and Cue Exposure in Cannabis Use Disorder

Assessment of harm reduction receipt and infectious diseases outcomes in United States Veterans with opioid use disorder and history of injection drug use

BackgroundInjection drug use (IDU) may lead to negative health outcomes and increased healthcare utilization. In US Veterans (USV) with opioid use disorder (OUD), there is sparse information about healthcare utilization, harm reduction prescription, and outcomes associated with IDU, including severe injection-related infections (SIRI). We assessed psychosocial factors, clinical outcomes, and harm reduction receipt in a cohort of USV with OUD, specifically focusing on persons who inject drugs (PWID).MethodsA retrospective cohort study was performed of USV aged ≥ 18 years with a diagnosis of OUD who presented to the Northport Veterans Affairs Medical Center (Long Island, NY) between 2012 and 2022. Demographics, psychosocial factors, history of human immunodeficiency virus (HIV), hepatitis C virus (HCV) infection, and healthcare utilization were compared by IDU status. Prescription of medications for opioid use disorder, naloxone and pre-exposure prophylaxis (PrEP) for HIV were also compared by IDU status. SIRI episodes and associated sequelae were characterized in USV with IDU.ResultsA total of 502 USV with OUD were included and 216 (43%) were PWID. Mean age was 52.6 years. PWID were more likely to use multiple stimulants (14.4% PWID vs. 7.3% non-PWID, p < 0.011), be hospitalized with an infection (26.4% PWID vs. 12.2% non-PWID, p < 0.001) and had more frequent inpatient admissions (n = 5.5 PWID vs. n = 3.51 non-PWID, p = 0.003). Among PWID, 134 (62%) had a history of HCV infection, 9 (4.2%) had HIV, and 35 (16.2%) had at least one SIRI episode. PWID had a higher frequency of current (51.9% PWID vs. 38.5% non-PWID, p = 0.003) or previous MOUD use (45.8% PWID vs. 31.1% non-PWID, p < 0.001). Overall PrEP receipt in our cohort (0.46% PWID vs. 1.4% non-PWID, p = 0.4) was low.ConclusionsUSV with OUD and a history of IDU had a high prevalence of concurrent stimulant use, HCV, SIRI episodes, and were more likely to be hospitalized than USV with OUD and no history of IDU. Harm reduction strategies such as MOUD or PrEP, can help decrease the risk of infectious diseases, yet PrEP was underutilized in our population regardless of IDU status. USV with OUD would benefit from improved integration of OUD treatment, infectious diseases clinical care and harm reduction interventions.

Multifunctional Neural Probes Enable Bidirectional Electrical, Optical, and Chemical Recording and Stimulation In Vivo.

Recording and modulation of neuronal activity enables the study of brain function in health and disease. While translational neuroscience relies on electrical recording and modulation techniques, mechanistic studies in rodent models leverage genetic precision of optical methods, such as optogenetics and fluorescent indicator imaging. In addition to electrical signal transduction, neurons produce and receive diverse chemical signals which motivate tools to probe and modulate neurochemistry. Although the past decade has delivered a wealth of technologies for electrophysiology, optogenetics, chemical sensing, and optical recording, combining these modalities within a single platform remains challenging. This work leverages materials selection and convergence fiber drawing to permit neural recording, electrical stimulation, optogenetics, fiber photometry, drug and gene delivery, and voltammetric recording of neurotransmitters within individual fibers. Composed of polymers and non-magnetic carbon-based conductors, these fibers are compatible with magnetic resonance imaging, enabling concurrent stimulation and whole-brain monitoring. Their utility is demonstrated in studies of the mesolimbic reward pathway by interfacing with the ventral tegmental area and nucleus accumbens in mice and characterizing the neurophysiological effects of a stimulant drug. This study highlights the potential of these fibers to probe electrical, optical, and chemical signaling across multiple brain regions in both mechanistic and translational studies.

Impact of baseline methamphetamine/amphetamine use on discontinuation of methadone and buprenorphine/naloxone among people with prescription-type opioid use disorder in Canada.

Although concurrent stimulant use is common among people with opioid use disorder (OUD), there is little evidence on its impacts on opioid agonist therapy (OAT) outcomes. This study sought to determine the impact of baseline methamphetamine/amphetamine use on discontinuation of OAT among individuals with prescription-type OUD (POUD) initiating methadone or buprenorphine/naloxone as part of a pragmatic randomized trial in Canada. Secondary analysis of a pan-Canadian pragmatic trial conducted between 2017 and 2020 comparing supervised methadone versus flexible take-home dosing buprenorphine/naloxone models of care. Cox proportional hazard models were used to evaluate the effect of baseline methamphetamine/amphetamine use (measured by urine drug test [UDT]) on two discontinuation outcomes (i.e., assigned OAT discontinuation, any OAT discontinuation). Two hundred nine (n = 209) participants initiated OAT, of which 96 (45.9%) had positive baseline methamphetamine/amphetamine UDT. Baseline methamphetamine/amphetamine use was associated with shorter median times in assigned OAT (21 vs. 168 days, hazard ratio [aHR] = 2.45, 95% confidence interval [CI] = 1.60-3.76) and any OAT (25 days vs. 168 days, aHR = 2.06, CI = 1.32-3.24). No interaction between methamphetamine/amphetamine and assigned OAT was observed for either outcome (p > .05). This study offers novel insights on the impact of methamphetamine/amphetamine use on OAT outcomes among people with POUD. Methamphetamine/amphetamine use was common and was associated with increased risk of OAT discontinuation. Supplementary interventions, including treatment for stimulant use, are needed to improve retention in OAT and optimize treatment outcomes in this population.

Effective connectivity of the human cortical face network through concurrent intracerebral electrical stimulation and frequency-tagged visual presentation

Effective connectivity of the human cortical face network through concurrent intracerebral electrical stimulation and frequency-tagged visual presentation

Interactive effect between transcranial focused ultrasound and transcranial magnetic stimulation on human motor cortex

Interactive effect between transcranial focused ultrasound and transcranial magnetic stimulation on human motor cortex