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Calcium activation of cortical neurons by continuous electrical stimulation: Frequency dependence, temporal fidelity, and activation density.

ABSTRACT: Electrical stimulation of the brain has become a mainstay of fundamental neuroscience research and an increasingly prevalent clinical therapy. Despite decades of use in basic neuroscience research and the growing prevalence of neuromodulation therapies, gaps in knowledge regarding activation or inactivation of neural elements over time have limited its ability to adequately interpret evoked downstream responses or fine-tune stimulation parameters to focus on desired responses. In this work, in vivo two-photon microscopy was used to image neuronal calcium activity in layer 2/3 neurons of somatosensory cortex (S1) in male C57BL/6J-Tg(Thy1-GCaMP6s)GP4.3Dkim/J mice during 30 s of continuous electrical stimulation at varying frequencies. We show frequency-dependent differences in spatial and temporal somatic responses during continuous stimulation. Our results elucidate conflicting results from prior studies reporting either dense spherical activation of somas biased toward those near the electrode, or sparse activation of somas at a distance via axons near the electrode. These findings indicate that the neural element specific temporal response local to the stimulating electrode changes as a function of applied charge density and frequency. These temporal responses need to be considered to properly interpret downstream circuit responses or determining mechanisms of action in basic science experiments or clinical therapeutic applications.

SUBMITTER: Michelson NJ

PROVIDER: S-EPMC6469875 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Calcium activation of cortical neurons by continuous electrical stimulation: Frequency dependence, temporal fidelity, and activation density.

Michelson Nicholas J NJ Eles James R JR Vazquez Alberto L AL Ludwig Kip A KA Kozai Takashi D Y TDY

Journal of neuroscience research 20181226 5

Electrical stimulation of the brain has become a mainstay of fundamental neuroscience research and an increasingly prevalent clinical therapy. Despite decades of use in basic neuroscience research and the growing prevalence of neuromodulation therapies, gaps in knowledge regarding activation or inactivation of neural elements over time have limited its ability to adequately interpret evoked downstream responses or fine-tune stimulation parameters to focus on desired responses. In this work, in v ...[more]

PMID: 30585651

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Project description:BackgroundThe mirror neuron system (MNS) plays a key role in the neural mechanism underlying motor learning and neural plasticity. Action observation (AO), action execution (AE), and a combination of both, known as action imitation (AI), are the most commonly used rehabilitation strategies based on MNS. It is possible to enhance the cortical activation area and amplitude by combining traditional neuromuscular electrical stimulation (NMES) with other top-down and active rehabilitation strategies based on the MNS theory.ObjectiveThis study aimed to explore the cortical activation patterns induced by NMES synchronized with rehabilitation strategies based on MNS, namely NMES+AO, NMES+AE, and NMES+AI. In addition, the study aimed to assess the feasibility of these three novel rehabilitative treatments in order to provide insights and evidence for the design, implementation, and application of brain-computer interfaces.MethodsA total of 70 healthy adults were recruited from July 2022 to February 2023, and 66 of them were finally included in the analysis. The cortical activation patterns during NMES+AO, NMES+AE, and NMES+AI were detected using the functional Near-Infrared Spectroscopy (fNIRS) technique. The action to be observed, executed, or imitated was right wrist and hand extension, and two square-shaped NMES electrodes were placed on the right extensor digitorum communis. A block design was adopted to evaluate the activation intensity of the left MNS brain regions.ResultsGeneral linear model results showed that compared with the control condition, the number of channels significantly activated (PFDR < 0.05) in the NMES+AO, NMES+AE, and NMES+AI conditions were 3, 9, and 9, respectively. Region of interest (ROI) analysis showed that 2 ROIs were significantly activated (PFDR < 0.05) in the NMES+AO condition, including BA6 and BA44; 5 ROIs were significantly activated in the NMES+AE condition, including BA6, BA40, BA44, BA45, and BA46; and 6 ROIs were significantly activated in the NMES+AI condition, including BA6, BA7, BA40, BA44, BA45, and BA46.ConclusionThe MNS was activated during neuromuscular electrical stimulation combined with an AO, AE, and AI intervention. The synchronous application of NMES and mirror neuron rehabilitation strategies is feasible in clinical rehabilitation. The fNIRS signal patterns observed in this study could be used to develop brain-computer interface and neurofeedback therapy rehabilitation devices.

Project description:BackgroundMethods for the electrical inhibition of cardiac excitation have long been sought to control excitability and conduction, but to date remain largely impractical. High-amplitude alternating current (AC) stimulation has been known to extend cardiac action potentials (APs), and has been recently exploited to terminate reentrant arrhythmias by producing reversible conduction blocks. Yet, low-amplitude currents at similar frequencies have been shown to entrain cardiac tissues by generation of repetitive APs, leading in some cases to ventricular fibrillation and hemodynamic collapse in vivo. Therefore, an inhibition method that does not lead to entrainment - irrespective of the stimulation amplitude (bound to fluctuate in an in vivo setting) - is highly desirable.Methodology/principal findingsWe investigated the effects of broader amplitude and frequency ranges on the inhibitory effects of extracellular AC stimulation on HL-1 cardiomyocytes cultured on microelectrode arrays, using both sinusoidal and square waveforms. Our results indicate that, at sufficiently high frequencies, cardiac tissue exhibits a binary response to stimulus amplitude with either prolonged APs or no effect, thereby effectively avoiding the risks of entrainment by repetitive firing observed at lower frequencies. We further demonstrate the ability to precisely define reversible local conduction blocks in beating cultures without influencing the propagation activity in non-blocked areas. The conduction blocks were spatiotemporally controlled by electrode geometry and stimuli duration, respectively, and sustainable for long durations (300 s).Conclusion/significanceInhibition of cardiac excitation induced by high-frequency AC stimulation exhibits a binary response to amplitude above a threshold frequency, enabling the generation of reversible conduction blocks without the risks of entrainment. This inhibition method could yield novel approaches for arrhythmia modeling in vitro, as well as safer and more efficacious tools for in vivo cardiac mapping and radio-frequency ablation guidance applications.

Dataset Information

Calcium activation of cortical neurons by continuous electrical stimulation: Frequency dependence, temporal fidelity, and activation density.

Publications

Calcium activation of cortical neurons by continuous electrical stimulation: Frequency dependence, temporal fidelity, and activation density.

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