Zhi-De Deng

Analysis of First-Derivative Based QRS Detection Algorithms

Accurate QRS detection is an important first step for the analysis of heart rate variability. Algorithms based on the differentiated ECG are computationally efficient and hence ideal for real-time analysis of large datasets. Here, we analyze traditional first-derivative based squaring function (Hamilton-Tompkins) and Hilbert transform-based methods for QRS detection and their modifications with improved detection thresholds. On a standard ECG dataset, the Hamilton-Tompkins algorithm had the highest detection accuracy (99.68% sensitivity, 99.63% positive predictivity) but also the largest time error. The modified Hamilton-Tompkins algorithm as well as the Hilbert transform-based algorithms had comparable, though slightly lower, accuracy; yet these automated algorithms present an advantage for real-time applications by avoiding human intervention in threshold determination. The high accuracy of the Hilbert transform-based method compared to detection with the second derivative of the ECG is ascribable to its inherently uniform magnitude spectrum. For all algorithms, detection errors occurred mainly in beats with decreased signal slope, such as wide arrhythmic beats or attenuated beats. For best performance, a combination of the squaring function and Hilbert transform-based algorithms can be applied such that differences in detection will point to abnormalities in the signal that can be further analyzed.

Electroconvulsive therapy stimulus parameters: rethinking dosage.

In this article, we review the parameters that define the electroconvulsive therapy (ECT) electrical stimulus and discuss their biophysical roles. We also present the summary metrics of charge and energy that are conventionally used to describe the dose of ECT and the rules commonly deployed to individualize the dose for each patient. We then highlight the limitations of these summary metrics and dosing rules in that they do not adequately capture the roles of the distinct stimulus parameters. Specifically, there is strong theoretical and empirical evidence that stimulus parameters (pulse amplitude, shape, and width, and train frequency, directionality, polarity, and duration) exert unique neurobiological effects that are important for understanding ECT outcomes. Consideration of the distinct stimulus parameters, in conjunction with electrode placement, is central to further optimization of ECT dosing paradigms to improve the risk-benefit ratio. Indeed, manipulation of specific parameters, such as reduction of pulse width and increase in number of pulses, has already resulted in dramatic reduction of adverse effects, while maintaining efficacy. Furthermore, the manipulation of other parameters, such as current amplitude, which are commonly held at fixed, high values, might be productively examined as additional means of targeting and individualizing the stimulus, potentially reducing adverse effects. We recommend that ECT dose be defined using all stimulus parameters rather than a summary metric. All stimulus parameters should be noted in treatment records and published reports. To enable research on optimization of dosing paradigms, we suggest that ECT devices provide capabilities to adjust and display all stimulus parameters.

Electric field strength and focality in electroconvulsive therapy and magnetic seizure therapy: a finite element simulation study

We present the first computational study comparing the electric field induced by various electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) paradigms. Four ECT electrode configurations (bilateral, bifrontal, right unilateral, and focal electrically administered seizure therapy) and three MST coil configurations (circular, cap, and double cone) were modeled. The model incorporated a modality-specific neural activation threshold. ECT (0.3 ms pulse width) and MST induced the maximum electric field of 2.1-2.5 V cm⁻¹ and 1.1-2.2 V cm⁻¹ in the brain, corresponding to 6.2-7.2 times and 1.2-2.3 times the neural activation threshold, respectively. The MST electric field is more confined to the superficial cortex compared to ECT. The brain volume stimulated was much larger with ECT (up to 100%) than with MST (up to 8.2%). MST with the double-cone coil was the most focal, and bilateral ECT was the least focal. Our results suggest a possible biophysical explanation of the reduced side effects of MST compared to ECT. Our results also indicate that the conventional ECT pulse amplitude (800-900 mA) is much higher than necessary for seizure induction. Reducing the ECT pulse amplitude should be explored as a potential means of diminishing side effects.

Coil design considerations for deep transcranial magnetic stimulation

OBJECTIVES To explore the field characteristics and design tradeoffs of coils for deep transcranial magnetic stimulation (dTMS). METHODS We simulated parametrically two dTMS coil designs on a spherical head model using the finite element method, and compare them with five commercial TMS coils, including two that are FDA approved for the treatment of depression (ferromagnetic-core figure-8 and H1 coil). RESULTS Smaller coils have a focality advantage over larger coils; however, this advantage diminishes with increasing target depth. Smaller coils have the disadvantage of producing stronger field in the superficial cortex and requiring more energy. When the coil dimensions are large relative to the head size, the electric field decay in depth becomes linear, indicating that, at best, the electric field attenuation is directly proportional to the depth of the target. Ferromagnetic cores improve electrical efficiency for targeting superficial brain areas; however magnetic saturation reduces the effectiveness of the core for deeper targets, especially for highly focal coils. Distancing winding segments from the head, as in the H1 coil, increases the required stimulation energy. CONCLUSIONS Among standard commercial coils, the double cone coil offers high energy efficiency and balance between stimulated volume and superficial field strength. Direct TMS of targets at depths of ~4 cm or more results in superficial stimulation strength that exceeds the upper limit in current rTMS safety guidelines. Approaching depths of ~6 cm is almost certainly unsafe considering the excessive superficial stimulation strength and activated brain volume. SIGNIFICANCE Coil design limitations and tradeoffs are important for rational and safe exploration of dTMS.

Regional electric field induced by electroconvulsive therapy in a realistic finite element head model: Influence of white matter anisotropic conductivity

We present the first computational study investigating the electric field (E-field) strength generated by various electroconvulsive therapy (ECT) electrode configurations in specific brain regions of interest (ROIs) that have putative roles in the therapeutic action and/or adverse side effects of ECT. This study also characterizes the impact of the white matter (WM) conductivity anisotropy on the E-field distribution. A finite element head model incorporating tissue heterogeneity and WM anisotropic conductivity was constructed based on structural magnetic resonance imaging (MRI) and diffusion tensor MRI data. We computed the spatial E-field distributions generated by three standard ECT electrode placements including bilateral (BL), bifrontal (BF), and right unilateral (RUL) and an investigational electrode configuration for focal electrically administered seizure therapy (FEAST). The key results are that (1) the median E-field strength over the whole brain is 3.9, 1.5, 2.3, and 2.6 V/cm for the BL, BF, RUL, and FEAST electrode configurations, respectively, which coupled with the broad spread of the BL E-field suggests a biophysical basis for observations of superior efficacy of BL ECT compared to BF and RUL ECT; (2) in the hippocampi, BL ECT produces a median E-field of 4.8 V/cm that is 1.5-2.8 times stronger than that for the other electrode configurations, consistent with the more pronounced amnestic effects of BL ECT; and (3) neglecting the WM conductivity anisotropy results in E-field strength error up to 18% overall and up to 39% in specific ROIs, motivating the inclusion of the WM conductivity anisotropy in accurate head models. This computational study demonstrates how the realistic finite element head model incorporating tissue conductivity anisotropy provides quantitative insight into the biophysics of ECT, which may shed light on the differential clinical outcomes seen with various forms of ECT, and may guide the development of novel stimulation paradigms with improved risk/benefit ratio.

Simultaneous transcranial magnetic stimulation and single-neuron recording in alert non-human primates

Transcranial magnetic stimulation (TMS) is a widely used, noninvasive method for stimulating nervous tissue, yet its mechanisms of effect are poorly understood. Here we report new methods for studying the influence of TMS on single neurons in the brain of alert non-human primates. We designed a TMS coil that focuses its effect near the tip of a recording electrode and recording electronics that enable direct acquisition of neuronal signals at the site of peak stimulus strength minimally perturbed by stimulation artifact in awake monkeys (Macaca mulatta). We recorded action potentials within ∼1 ms after 0.4-ms TMS pulses and observed changes in activity that differed significantly for active stimulation as compared with sham stimulation. This methodology is compatible with standard equipment in primate laboratories, allowing easy implementation. Application of these tools will facilitate the refinement of next generation TMS devices, experiments and treatment protocols.

Coil design considerations for deep-brain transcranial magnetic stimulation (dTMS)

Deep-brain transcranial magnetic stimulation (dTMS) could provide new, non-invasive therapeutic options for various psychiatric and neurological disorders. Figures of merit (FoMs) are proposed to evaluate and compare dTMS coil designs. These FoMs characterize the depth of electric field penetration, scalp stimulation, focality, and energy. Two coil configurations potentially suitable for dTMS are analyzed: circular crown coil and C-core coil. These coils have significantly less attenuation of the electric field strength in depth, compared to conventional TMS coils. In the limiting case as the coil dimensions become large relative to the head, the electric field decay in depth becomes linear, which indicates that, at best, the electric field attenuation is directly proportional to the depth of the target. The charge density and heating induced in the brain are at safe levels, but the risk of unintended neuromodulation and seizures with dTMS has to be evaluated further. Preliminary simulation results suggest that the crown coil has the best overall performance for dTMS. Finally, synchronous firing of all TMS coil elements appears more effective at stimulating deep neurons than is sequential firing.

Effect of anatomical variability on neural stimulation strength and focality in electroconvulsive therapy (ECT) and magnetic seizure therapy (MST)

We present a quantitative comparison of two metrics-neural stimulation strength and focality-in electrocon-vulsive therapy (ECT) and magnetic seizure therapy (MST) using finite-element method (FEM) simulation in a spherical head model. Five stimulation modalities were modeled, including bilateral ECT, unilateral ECT, focal electrically administered seizure therapy (FEAST), and MST with circular and double-cone coils, with stimulation parameters identical to those applied in clinical practice. We further examine the effect on the stimulation metrics of individual-, sex- and age-related variability in tissue layer thickness and conductivity. Neural stimulation by MST is shown to be more focal and superficial than ECT. This result suggests that it may be advantageous to reduce the current used in ECT. The stimulation strength in MST is also less sensitive to variations in head geometry and tissue conductivity than in ECT. Individualization of pulse amplitude in both ECT and MST could compensate for anatomical variability, which could lead to more consistent clinical outcomes.

Heart rate variability in pediatric obstructive sleep apnea.

Obstructive sleep apnea syndrome (OSAS) is observed in approximately 2% of children. Heart rate variability (HRV) is a potentially simple, non-invasive diagnostic screening tool for OSAS. In this study, we investigated the diagnostic potential of HRV using power spectral analysis, numerical titration, sample entropy, and detrended fluctuation analysis. Effects of sleep stages (REM and NREM sleep) are evaluated. The results show that the heart rate chaos intensity, as measured by the noise limit in numerical titration, is significantly higher during REM sleep than NREM sleep in all patient groups. By using the receiver-operating characteristic analysis, the detection of OSAS yielded a specificity of 72.2% and sensitivity of 81.3% using the numerical-titration technique. The findings suggest that sleep state and disordered breathing are important determinants of cardiac autonomic control. Nonlinear techniques such as numerical titration, when used in conjunction with spectral analysis of HRV could be an effective screening tool for pediatric OSAS

Multifactorial determinants of the neurocognitive effects of electroconvulsive therapy.

For many patients with neuropsychiatric illnesses, standard psychiatric treatments with mono or combination pharmacotherapy, psychotherapy, and transcranial magnetic stimulation are ineffective. For these patients with treatment-resistant neuropsychiatric illnesses, a main therapeutic option is electroconvulsive therapy (ECT). Decades of research have found ECT to be highly effective; however, it can also result in adverse neurocognitive effects. Specifically, ECT results in disorientation after each session, anterograde amnesia for recently learned information, and retrograde amnesia for previously learned information. Unfortunately, the neurocognitive effects and underlying mechanisms of action of ECT remain poorly understood. The purpose of this paper was to synthesize the multiple moderating and mediating factors that are thought to underlie the neurocognitive effects of ECT into a coherent model. Such factors include demographic and neuropsychological characteristics, neuropsychiatric symptoms, ECT technical parameters, and ECT-associated neurophysiological changes. Future research is warranted to evaluate and test this model, so that these findings may support the development of more refined clinical seizure therapy delivery approaches and efficacious cognitive remediation strategies to improve the use of this important and widely used intervention tool for neuropsychiatric diseases.