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Deng, Z.-D.

Publications and source records attributed to Deng, Z.-D..

28 records · Page 2Linked to original sources

Real-time computation of transcranial magnetic stimulation electric fields using self-supervised deep learning

Electric fields (E-fields) induced by transcranial magnetic stimulation (TMS) can be modeled using partial differential equations (PDEs). Using state-of-the-art finite-element methods (FEM), it often takes tens of seconds to solve the PDEs for computing a high-resolution E-field, hampering the wide application of the E-field modeling in practice and research. To improve the E-field modelings computational efficiency, we developed a self-supervised deep learning (DL) method to compute precise TMS E-fields. Given a head model and the primary E-field generated by TMS coils, a DL model was built to generate a E-field by minimizing a loss function that measures how well the generated E-field fits the governing PDE. The DL model was trained in a self-supervised manner, which does not require any external supervision. We evaluated the DL model using both a simulated sphere head model and realistic head models of 125 individuals and compared the accuracy and computational speed of the DL model with a state-of-the-art FEM. In realistic head models, the DL model obtained accurate E-fields that were significantly correlated with the FEM solutions. The DL model could obtain precise E-fields within seconds for whole head models at a high spatial resolution, faster than the FEM. The DL model built for the simulated sphere head model also obtained an accurate E-field whose average difference from the analytical E-fields was 0.0054, comparable to the FEM solution. These results demonstrated that the self-supervised DL method could obtain precise E-fields comparable to the FEM solutions with improved computational speed.

neuroscience↗

Alpha oscillatory activity causally linked to working memory retention: insights from online phase-locking closed-loop transcranial alternating current stimulation (tACS)

Although previous studies have reported correlations between alpha oscillations and the "retention" sub-process of working memory (WM), causal evidence has been limited in human neuroscience due to the lack of delicate modulation of human brain. Conventional tACS is not suitable for demonstrating the causal evidence for parietal alpha oscillations in WM retention because of its inability to modulate brain oscillations within a short period (i.e., the retention sub-process). Here, we developed an online phase-corrected closed-loop transcranial alternating current stimulation (tACS) system capable of precisely correcting for the phase differences between tACS and concurrent endogenous oscillations. This system permits both up- and down-regulation of brain oscillations at the target stimulation frequency within a short stimulation period, and is here applied to empirically demonstrate that parietal alpha oscillations causally relate to WM retention. Our experimental design included both in-phase and anti-phase alpha-tACS applied to 39 participants during the retention sub-processes of a modified Sternberg paradigm. Compared to in-phase alpha-tACS, anti-phase alpha-tACS decreased both WM performance and alpha activity. Moreover, the in-phase tACS-induced changes in WM performance were positively correlated with alpha oscillatory activity. These findings strongly support a causal link between alpha oscillations and WM retention, and illustrate the broad application prospects of phase-corrected tACS.

neuroscience↗

Development of a novel connectivity-based electric-field modelling approach for individualized targeting of transcranial magnetic stimulation treatment.

BackgroundResting state functional connectivity (rsFC) offers promise for individualizing stimulation targets for transcranial magnetic stimulation (TMS) treatments. However current targeting approaches do not account for non-focal TMS effects or large-scale connectivity patterns. To overcome these limitations, we propose a novel targeting optimization approach that combines whole-brain rsFC and electric-field (e-field) modelling to identify single-subject, symptom-specific TMS targets. MethodsIn this proof of concept study, we recruited 91 anxious misery (AM) patients and 25 controls. We measured depression symptoms (MADRS/HAMD) and recorded rsFC. We used a PCA regression to predict symptoms from rsFC and estimate the parameter vector, for input into our e-field augmented model. We modeled 17 left dlPFC and 7 M1 sites using 24 equally spaced coil orientations. We computed single-subject predicted {Delta}MADRS/HAMD scores for each site/orientation using the e-field augmented model, which comprises a linear combination of the following elementwise products 1) the estimated connectivity/symptom coefficients, 2) a vectorized e-field model for site/orientation, 3) the pre-treatment rsFC matrix, scaled by a proportionality constant. ResultsIn AM patients, our pre-stimulation connectivity-based model predicted a significant decrease depression for sites near BA46, but not M1 for coil orientations perpendicular to the cortical gyrus. In control subjects, no site/orientation combination showed a significant predicted change. DiscussionThese results corroborate previous work suggesting the efficacy of left dlPFC stimulation for depression treatment, and predict better outcomes with individualized targeting. They also suggest that our novel connectivity-based e-field modelling approach may effectively identify potential TMS treatment responders and individualize TMS targeting to maximize the therapeutic impact.

neuroscience↗

A Double-Blind Pilot Dosing Study of Low Field Magnetic Stimulation (LFMS) for Treatment-Resistant Depression (TRD)

Low Field Magnetic Stimulation is a potentially rapid-acting treatment for depression with mood-enhancing effects in as little as one 20-minute session. The most convincing data for LFMS has come from treating bipolar depression. We examined whether LFMS also has rapid mood-enhancing effects in treatment-resistant major depressive disorder, and whether these effects are dose-dependent. We hypothesized that a single 20-min session of LFMS would reduce depressive symptom severity and that the magnitude of this change would be greater after three 20-min sessions than after a single 20-min session. In a double-blind randomized controlled trial, 30 participants (age 21-65) with treatment-resistant depression were randomized to three 20-minute active or sham LFMS treatments with 48 hours between treatments. Response was assessed immediately following LFMS treatment using the 6-item Hamilton Depression Rating Scale (HAMD-6), the Positive and Negative Affect Scale (PANAS) and the Visual Analog Scale. Following the third session of LFMS, the effect of LFMS on VAS and HAMD-6 was superior to sham (F(1, 24) = 7.45, p = 0.03, Holm-Bonferroni corrected; F(1,22) = 6.92, p = 0.03, Holm-Bonferroni corrected, respectively). There were no differences between sham and LFMS following the initial or second session with the effect not becoming significant until after the third session. Three 20-minute LFMS sessions were required for active LFMS to have a mood-enhancing effect for individuals with treatment-resistant depression. As this effect may be transient, future work should address dosing schedules of longer treatment course as well as biomarker-based targeting of LFMS to optimize patient selection and treatment outcomes.

clinical trials↗

Non-High Frequency Heart Rate Chaos: A Noninvasive Marker of REM Sleep and Obstructive Sleep Apnea Syndrome in Children

Obstructive sleep apnea syndrome (OSAS) is a highly prevalent condition associated with considerable metabolic, cardiovascular, and neurocognitive morbidity. Childhood OSAS is underdiagnosed due to a limited number of sleep laboratories and the lack of a screening test, and the subtlety of daytime symptoms in children compared to adults. A potential marker of OSAS is apnea-induced sympathoexcitation, which is likely to be exacerbated during rapid-eyemovement (REM) sleep. However, traditional methods of assessing sympathetic activity are either too invasive or insensitive/nonspecific for clinical use, particularly as a screening test. Study population comprised pediatric patients with OSAS (16 moderate/severe, 18 mild) and 18 normal non-snoring controls. We show that the chaotic dynamics of heart rate variability (HRV) as assessed by a sensitive noise titration assay is significantly increased during REM compared to non-REM sleep in children, particularly those with OSAS. The increase in heart rate chaos prevails in the face of decreased parasympathetic-mediated high-frequency component of the HRV power spectrum, indicating that the chaos was correlated to sympathetic instead of parasympathetic activity. Receiver operating characteristic analysis shows that such non-high frequency chaos reveals changing sympathetic-parasympathetic activities that are not discernible by conventional HRV metrics such as low- to high-frequency power ratio or sample entropy, with sensitivity and specificity sufficient to detect even mild OSAS in children. Results suggest a possible role for non-high frequency heart rate chaos as a selective noninvasive marker of sympathoexcitation in REM sleep, OSAS and potentially other cardiovascular abnormalities such as congestive heart failure.

physiology↗

Utilizing Transcranial Direct Current Stimulation to Enhance Laparoscopic Technical Skills Training: A Randomized Controlled Trial

This study aimed to test the efficacy of transcranial direct current stimulation (tDCS) during laparoscopic skill training to determine if it has the capacity to accelerate technical skill acquisition. tDCS is a non-invasive brain stimulation technique that delivers constant, low electrical current resulting in changes to cortical excitability and prior work suggests it may enhance motor learning. We evaluate for the first time the potential of tDCS, coupled with motor skill training, to accelerate the development of laparoscopic technical skills. In this pre-registered, double-blinded and sham-controlled study, 60 healthy subjects were randomized into sham or active tDCS in either bilateral primary motor cortex (bM1) or supplementary motor area (SMA) electrode configurations. All subjects practiced the Fundamental of Laparoscopic Surgery Peg Transfer Task during a pre-test, six 20-minute training sessions, and a post-test. The primary outcome was change in laparoscopic skill performance over time, quantified by improvement in performance according to a seconds-per-object calculated score accounting for errors. Sixty participants were randomized equally into the three training cohorts (active bM1, active SMA, sham). The active groups had significantly greater improvement in performance from pre-test to post-test compared to the sham groups (108 vs 76 seconds, p = 0.018). Both bM1 and SMA active cohorts had significantly greater improvement in learning (p < 0.01), achieving the same skill level in 4 sessions compared to the 6 sessions required of the sham cohort. The SMA cohort had more variability in performance compared to the bM1 and control cohorts. Laparoscopic skill training with active, bM1 or SMA, tDCS exhibited significantly greater learning relative to training with sham tDCS. The potential for tDCS to enhance the training of surgical skills merits further investigation to determine if these preliminary results may be replicated.

clinical trials↗

Modulation of Resting Connectivity Between the Mesial Frontal Cortex and Basal Ganglia

The mesial prefrontal cortex, cingulate cortex and the ventral striatum are key nodes of the human mesial fronto-striatal circuit involved in decision-making and executive function and pathological disorders. Here we ask whether deep wide-field repetitive transcranial magnetic stimulation (rTMS) targeting the mesial prefrontal cortex (MPFC) influences resting state functional connectivity. In Study 1, we examined functional connectivity using resting state multi-echo and independent components analysis in 154 healthy subjects to characterize default connectivity in the MPFC and mid-cingulate cortex (MCC). In Study 2, we used inhibitory, 1 Hz deep rTMS with the H7-coil targeting MPFC and dorsal anterior cingulate (dACC) in a separate group of 20 healthy volunteers and examined pre-and post-TMS functional connectivity using seed-based and independent components analysis. In Study 1, we show that MPFC and MCC have distinct patterns of functional connectivity with MPFC-ventral striatum showing negative, whereas MCC-ventral striatum showing positive functional connectivity. Low-frequency rTMS decreased functional connectivity of MPFC and dACC with the ventral striatum. We further showed enhanced connectivity between MCC and ventral striatum. These findings emphasize how deep inhibitory rTMS using the H7-coil can influence underlying network functional connectivity by decreasing connectivity of the targeted MPFC regions, thus potentially enhancing response inhibition and decreasing drug cue reactivity processes relevant to addictions. The unexpected finding of enhanced default connectivity between MCC and ventral striatum may be related to the decreased influence and connectivity between the MPFC and MCC. These findings are highly relevant to the treatment of disorders relying on the mesioprefrontal-cingulo-striatal circuit.

neuroscience↗

Neural circuit repair by low-intensity magnetic stimulation requires cryptochrome

Magnetic brain stimulation is a promising treatment in neurology and psychiatry, but clinical outcomes are variable. Unfortunately, mechanisms underlying magnetic stimulation effects are ill-defined, which impedes the development of stimulation protocols appropriate for different neurological conditions. Here we show, in vivo and ex vivo, that repetitive transcranial magnetic stimulation at low-intensity (LI-rTMS) induces axon outgrowth and synaptogenesis to repair a neural circuit. This repair depends on stimulation pattern, with complex patterns being particularly effective, and its mechanism requires the presence of cryptochrome (Cry), a putative magneto-receptor. Effective LI-rTMS patterns altered expression of Cry target genes known to promote neuronal repair. Because LI-rTMS generates electric fields too weak to depolarise neurons, these findings indicate that the magnetic field itself induces the repair. Our data open a new framework for magnetic stimulation - cryptochrome-mediated molecular and structural neuroplasticity. This information suggests new routes to treatments specific for each neurological disease.

neuroscience↗

Design and Analysis of a Whole Body Non-Contact Electromagnetic Stimulation Device with Field Modulation

This study describes a whole-body, non-contact electromagnetic stimulation device based on the concept of a conventional MRI Radio Frequency (RF) resonating coil, but at a much lower resonant frequency (100-150 kHz), with a field modulation option (0.5-100 Hz) and with an input power of up to 3 kW. Its unique features include a high electric field level within the biological tissue due to the resonance effect and a low power dissipation level, or a low Specific Absorption Rate (SAR), in the body itself. Because of its large resonator volume together with non-contact coupling, the subject may be located anywhere within the coil over a longer period at moderate and safe electric field levels. The electric field effect does not depend on body position within the resonator. However, field penetration is deep anywhere within the body, including the extremities where muscles, bones, and peripheral tissues are mostly affected. A potential clinical application of this device is treatment of chronic pain. Substantial attention is paid to device safety; this includes both AC power safety and exposure of human subjects to electromagnetic fields. In the former case, we employ inductive coupling which eliminates a direct current path from AC power to the coil. Our design enhances overall device safety at any power level, even when operated under higher-power conditions. Human exposure to electromagnetic fields within the coil is evaluated by performing modeling with two independent numerical methods and with an anatomically realistic multi-tissue human phantom. We show that SAR levels within the body correspond to International Electrotechnical Commission (IEC) safety standards when the input power level of the amplifier driver does not exceed 3 kW. We also show that electric field levels generally comply with International Commission on Non-Ionizing Radiation Protection safety standards if the input power level does not exceed 1.5 kW.

bioengineering↗

Statistical Model of Motor Evoked Potentials for Simulation of Transcranial Magnetic and Electric Stimulation

Motor evoked potentials (MEPs) are widely used for biomarkers and dose individualization in transcranial stimulation. The large variability of MEPs requires sophisticated methods of analysis to extract information fast and correctly. However, models of MEPs that represent their characteristic features are lacking. This work presents a statistical model that can simulate long sequences of individualized MEP amplitude data with properties matching experimental observations. The MEP model includes three sources of trial-to-trial variability to mimic excitability fluctuations, variability in the neural and muscular pathways, and physiological and measurement noise. It also generates virtual human subject data from statistics of population variability. All parameters are extracted as statistical distributions from experimental data from the literature. The model exhibits previously described features, such as stimulusintensity-dependent MEP amplitude distributions, including bimodal ones. The model can generate long sequences of test data for individual subjects with specified parameters or for subjects from a virtual population. The presented MEP model is the most detailed to date and can be used for the development and implementation of dosing and biomarker estimation algorithms for transcranial stimulation.

physiology↗