A brief overview of passive microvalves in microfluidics: Mechanism, manufacturing, and applications.

Microvalves play a crucial role in manipulating fluid states within a microfluidic system and are finding widespread applications in fields such as biology, medicine, and environmental preservation. Leveraging the characteristics and features of microvalves enables the realization of various complicated microfluidic functions. Continuous advancement in the manufacturing process contributes to more flexible control modes for passive microvalves. As a consequence, these valves are progressively shrinking in size while simultaneously improving in precision and stability. Although active microvalves have the benefits of low leakage, rapid response time, and wide adaptability range, the energy supply system limits the size and even their applicability in integration and miniaturization. In comparison, passive microvalves have the advantage of relying solely on the fluid flow or fluid driving pressure to control the open/close of fluid flow over active microvalves, in spite of having slightly reduced control accuracy. Their self-sustaining feature is highly consistent with the need for assembly and miniaturization in the point-of-care testing technology. Hence, these valves have attracted significant interest for research and application purposes. This review focuses on the recent literature on passive microvalves and details existing passive microvalves from three different aspects: operating principle, processing method, and applications. This work aims to increase the visibility of passive microvalves among researchers and enhance their comprehension by classifying them according to the aforementioned three aspects, facilitating the practical applications and further developments of passive microvalves. Additionally, this paper is expected to serve as a comprehensive and systematic reference for interdisciplinary researchers that intend to design related microfluidic systems.

Fronto-medial electrode placement for electroconvulsive treatment of depression.

Electroconvulsive therapy (ECT) is the most effective treatment for severe treatment-resistant depression but concern about cognitive side-effects, particularly memory loss, limits its use. Recent observational studies on large groups of patients who have received ECT report that cognitive side-effects were associated with electric field (EF) induced increases in hippocampal volume, whereas therapeutic efficacy was associated with EF induced increases in sagittal brain structures. The aim in the present study was to determine whether a novel fronto-medial (FM) ECT electrode placement would minimize electric fields in bilateral hippocampi (HIP) whilst maximizing electric fields in dorsal sagittal cortical regions. An anatomically detailed computational head model was used with finite element analysis, to calculate ECT-induced electric fields in specific brain regions identified by translational neuroimaging studies of treatment-resistant depressive illness, for a range of electrode placements. As hypothesized, compared to traditional bitemporal (BT) electrode placement, a specific FM electrode placement reduced bilateral hippocampal electric fields two-to-three-fold, whilst the electric fields in the dorsal anterior cingulate (dAC) were increased by approximately the same amount. We highlight the clinical relevance of this specific FM electrode placement for ECT, which may significantly reduce cognitive and non-cognitive side-effects and suggest a clinical trial is indicated.

Effects of Degrees of Degeneration on the Electrical Excitation of Human Spiral Ganglion Neurons Based on a High-Resolution Computer Model.

After hearing loss retrograde degeneration of spiral ganglion neurons (SGNs) has been described. Studies modeling the effects of degeneration mostly omitted peripheral processes (dendrites). Recent experimental observations indicated that degenerating SGNs manifested also a reduced diameter of their dendrites. We simulated populations of 400 SGNs inside a high resolution cochlear model with a cochlear implant, based on µCT scans of a human temporal bone. Cochlear implant stimuli were delivered as biphasic pulses in a monopolar configuration. Three SGN situations were simulated, based on our previous measurements of human SGN dendrites: (A) SGNs with intact dendrites (before degeneration), (B) degenerating SGNs, dendrites with a smaller diameter but original length, (C) degenerating SGNs, dendrites omitted. SGN fibers were mapped to characteristic frequency, and place pitch was estimated from excitation profiles. Results from degenerating SGNs (B, C) were similar. Most action potentials were initiated in the somatic area for all cases (A, B, C), except for areas near stimulating electrodes in the apex with intact SGNs (A), where action potentials were initiated in the distal dendrite. In most cases, degenerating SGNs had lower thresholds than intact SGNs (A) (down to -2 dB). Excitation profiles showed increased ectopic activation, i.e., activation of unintended neuronal regions, as well as similar neuronal regions excited by different apical electrodes, for degenerating SGNs (B, C). The estimated pitch showed cases of pitch reversals in apical electrodes for intact SGNs (A), as well as mostly identical pitches evoked by the four most apical electrodes for degenerating SGNs (B, C). In conclusion, neuronal excitation profiles to electrical stimulation exhibited similar traits in both ways of modeling SGN degeneration. Models showed degeneration of dendrites caused increased ectopic activation, as well as similar excitation profiles and pitch evoked by different apical electrodes. Therefore, insertion of electrodes beyond approximately 450° may not provide any benefit if SGN dendrites are degenerated.

Effects of modifying the electrode placement and pulse width on cognitive side effects with unilateral ECT: A pilot randomised controlled study with computational modelling.

BACKGROUND: The electrode placement and pulse width for electroconvulsive therapy (ECT) are important treatment parameters associated with ECT related retrograde memory side-effects. Modification of these parameters with right unilateral (RUL) ECT may have utility for further reducing these side-effects. OBJECTIVE: This study explored use of the frontoparietal (FP) placement for reducing retrograde memory side effects with ECT. We hypothesised that superior retrograde memory outcomes would occur with FP compared to temporoparietal (TP) placement and with ultrabrief (UB: 0.3 ms) compared to brief pulse (BP: 1.0 ms) width ECT. METHODS: In this randomised cross-over, double-blinded study, participants received a single treatment of BP TP, BP FP, UB TP and UB FP ECT. Neuropsychological testing was conducted prior to and immediately following each treatment. Computational modelling was conducted to explore associations between E-fields in regions-of-interest associated with memory. RESULTS: Nine participants completed the study. The FP placement was not superior to TP for retrograde memory outcomes. For both electrode placements UB pulse width was associated with significantly better visual retrograde memory compared to BP (p < .05). With TP ECT, higher E-fields in regions-of-interest were significantly associated with greater visual retrograde memory side-effects (hippocampi: r = -0.77, p = .04; inferior frontal gyri: r = -0.92, p < .01; middle frontal gyri: r = -0.84, p = .02). CONCLUSIONS: Modification of pulse-width had greater effects than electrode placement for reducing retrograde memory side-effects with RUL ECT. Preliminary findings suggested that higher E-fields may be associated with greater cognitive side-effects with ECT.

Electrical stimulation in the cochlea: Influence of modiolar microstructures on the activation of auditory nerve fibres.

Existing computational studies of cochlear implants have demonstrated that the structural detail of threedimensional (3D) cochlear models exerts influence on the current spread within the cochlea. Nevertheless, the significance of including the microstructures inside the modiolar bone in a cochlear model is still unclear in the literature. We employed two different multi-compartment neuron models to simulate auditory nerve fibres, and compared response characteristics of the fibre population between a detailed and a simplified 3D cochlear model. Results showed that although the prediction of firing is dependent on the details of the neuron model, the responses of the fibre population to the electrical stimulus, especially the location of the initiation of action potential, varied between the detailed and the simplified models. Therefore, the inclusion of the modiolar microstructures in a cochlear model may be necessary for fully understanding the firing of auditory nerve fibres.

Dynamic screening and printing of single cells using a microfluidic chip with dual microvalves.

Inoculation of single cells into separate culture chambers is one of the key requirements in single-cell analysis. This paper reports an innovative microfluidic chip integrating two pneumatic microvalves to screen and print single cells onto a well plate. The upper and lower size limits of cells can be dynamically controlled by regulating the deformation of two adjacent microvalves. Numerical simulations were employed to systematically study the influence of membrane dimensions and pressure on the deflection of a valve. A mathematical model was then modified to predict the size of cells captured by a microvalve at various pressures. The membrane deflection was further studied using confocal imaging. The critical pressure trapping beads of various sizes was experimentally determined. These experiments validated the accuracy of both numerical simulations and the mathematical model. Furthermore, single beads and endothelial cells with the desired size range were screened using dual valves and printed onto well plates with 100% efficiency. Viability studies suggested that the screening process had no significant impact on cells. This device enables dynamic regulation of both the lower and the upper size limits of cells for printing. It has significant application potential in inoculating cells with desired sizes for various fields such as clonal expansion, monoclonality development and single-cell genomic studies.

Comparison of Multi-Compartment Cable Models of Human Auditory Nerve Fibers.

Background: Multi-compartment cable models of auditory nerve fibers have been developed to assist in the improvement of cochlear implants. With the advancement of computational technology and the results obtained from in vivo and in vitro experiments, these models have evolved to incorporate a considerable degree of morphological and physiological details. They have also been combined with three-dimensional volume conduction models of the cochlea to simulate neural responses to electrical stimulation. However, no specific rules have been provided on choosing the appropriate cable model, and most models adopted in recent studies were chosen without a specific reason or by inheritance. Methods: Three of the most cited biophysical multi-compartment cable models of the human auditory nerve, i.e., Rattay et al. (2001b), Briaire and Frijns (2005), and Smit et al. (2010), were implemented in this study. Several properties of single fibers were compared among the three models, including threshold, conduction velocity, action potential shape, latency, refractory properties, as well as stochastic and temporal behaviors. Experimental results regarding these properties were also included as a reference for comparison. Results: For monophasic single-pulse stimulation, the ratio of anodic vs. cathodic thresholds in all models was within the experimental range despite a much larger ratio in the model by Briaire and Frijns. For biphasic pulse-train stimulation, thresholds as a function of both pulse rate and pulse duration differed between the models, but none matched the experimental observations even coarsely. Similarly, for all other properties including the conduction velocity, action potential shape, and latency, the models presented different outcomes and not all of them fell within the range observed in experiments. Conclusions: While all three models presented similar values in certain single fiber properties to those obtained in experiments, none matched all experimental observations satisfactorily. In particular, the adaptation and temporal integration behaviors were completely missing in all models. Further extensions and analyses are required to explain and simulate realistic auditory nerve fiber responses to electrical stimulation.

Computational comparison of conventional and novel electroconvulsive therapy electrode placements for the treatment of depression.

BACKGROUND: Electroconvulsive therapy (ECT) is a highly effective treatment for severe psychiatric disorders. Despite its high efficacy, the use of ECT would be greater if the risk of cognitive side effects were reduced. Over the last 20 years, developments in ECT technique, including improvements in the dosing methodology and modification of the stimulus waveform, have allowed for improved treatment methods with reduced adverse cognitive effects. There is increasing evidence that the electrode placement is important for orienting the electrical stimulus and therefore modifying treatment outcomes, with potential for further improvement of the placements currently used in ECT. OBJECTIVE: We used computational modelling to perform an in-depth examination into regional differences in brain excitation by the ECT stimulus for several lesser known and novel electrode placements, in order to investigate the potential for an electrode placement that may optimise clinical outcomes. METHODS: High resolution finite element human head models were generated from MRI scans of three subjects. The models were used to compare regional differences in average electric field (EF) magnitude among a total of thirteen bipolar ECT electrode placements, i.e. three conventional placements as well as ten lesser known and novel placements. RESULTS AND CONCLUSION: In this exploratory study on a systemic comparison of thirteen ECT electrode placements, the EF magnitude at regions of interest (ROIs) was highly dependent upon the position of both electrodes, especially the ROIs close to the cortical surface. Compared to conventional right-unilateral (RUL) ECT using a temporo-parietal placement, fronto-parietal and supraorbito-parietal RUL also robustly stimulated brain regions considered important for efficacy, while sparing regions related to cognitive functions, and may be a preferrable approach to the currently used placement for RUL ECT. The simulations also found that regional average EF magnitude varied between individual subjects, due to factors such as head size, and results also depended on the size of the defined ROI.

Electrical Stimulation in the Human Cochlea: A Computational Study Based on High-Resolution Micro-CT Scans.

Background: Many detailed features of the cochlear anatomy have not been included in existing 3D cochlear models, including the microstructures inside the modiolar bone, which in turn determines the path of auditory nerve fibers (ANFs). Method: We captured the intricate modiolar microstructures in a 3D human cochlea model reconstructed from µCT scans. A new algorithm was developed to reconstruct ANFs running through the microstructures within the model. Using the finite element method, we calculated the electrical potential as well as its first and second spatial derivatives along each ANF elicited by the cochlear implant electrodes. Simulation results of electrical potential was validated against intracochlear potential measurements. Comparison was then made with a simplified model without the microstructures within the cochlea. Results: When the stimulus was delivered from an electrode located deeper in the apex, the extent of the auditory nerve influenced by a higher electric potential grew larger; at the same time, the maximal potential value at the auditory nerve also became larger. The electric potential decayed at a faster rate toward the base of the cochlea than toward the apex. Compared to the cochlear model incorporating the modiolar microstructures, the simplified version resulted in relatively small differences in electric potential. However, in terms of the first and second derivatives of electric potential along the fibers, which are relevant for the initiation of action potentials, the two models exhibited large differences: maxima in both derivatives with the detailed model were larger by a factor of 1.5 (first derivative) and 2 (second derivative) in the exemplary fibers. More importantly, these maxima occurred at different locations, and opposite signs were found for the values of second derivatives between the two models at parts along the fibers. Hence, while one model predicts depolarization and spike initiation at a given location, the other may instead predict a hyperpolarization. Conclusions: Although a cochlear model with fewer details seems sufficient for analysing the current spread in the cochlear ducts, a detailed-segmented cochlear model is required for the reconstruction of ANF trajectories through the modiolus, as well as the prediction of firing thresholds and spike initiation sites.

XLIF interbody cage reduces stress and strain of fixation in spinal reconstructive surgery in comparison with TLIF cage with bilateral or unilateral fixation: a computational analysis.

In treating recalcitrant low back pain, extreme lateral lumbar interbody fusion (XLIF) with a large cage is reported to have better stability compared to approach of transforaminal lumbar interbody fusion (TLIF) using a small cage. In addition, bilateral pedicle screw fixation (PSF) in comparison with unilateral fixation achieved no inferior fusion rate, but with a significant reduction in operation time and blood loss. The aim of the study was to understand the mechanism underpinning the stability of lumbar interbody fusion using different cage sizes with unilateral or bilateral PSF. A computer model of human lumbar vertebrae L4 and L5 with implants was reconstructed based on CT scans and simulated in Ansys Workbench. Simulation results demonstrated that for either XLIF or TLIF cages, the maximum values of rod stress were comparable with bilateral and unilateral PSF. However, the stability was considerably reduced with unilateral PSF for TLIF due to significantly increased facet joint strain for TLIF; whereas for XLIF with left unilateral PSF, the max facet joint strain was comparable to bilateral PSF, possibly due to facet tropism of this specific subject.

Tractography Analysis for Electroconvulsive Therapy.

Computational human head models have been used in electrophysiological studies, and they have been able to provide useful information that is unable or difficult to acquire from experimental or imaging studies. However, most of these models are purely volume conductor models that overlooked the electric excitability of axons in the white matter of the brain. This study combined a finite element (FE) model of electroconvulsive therapy (ECT) with a whole-brain tractography analysis as well as the cable theory of neuronal excitation. We have reconstructed a whole-brain tractogram with 500 neural fibres from the diffusion-weighted magnetic resonance scans, and extracted the information on electrical potential from the FE ECT model of the same head. We then calculated the first and second spatial derivatives of the electrical potential, which describes the activating function for homogenous axons and investigated sensitive regions of white matter activation.

Influence of the Cochlear Implant Electrode Array Placement on the Current Spread in the Cochlea.

Three-dimensional (3D) computational models of the inner ear have been utilised to assist in investigating the factors that influence cochlear implant (CI) outcomes. A volume conductor cochlear model with an implanted electrode array was reconstructed from X-ray microtomography $(\mu$ CT) scans of a cadaveric human temporal bone. To mimic an in-vivo setting, the cochlea was embedded in a head model. The finite element (FE) method was used to analyse the electrical potential $\varphi$ in the cochlear nerve as a result of CI stimulation. In order to study the influence of electrode array placement on the current spread within the cochlea and the modiolus, computer simulations with six electrode array placements were conducted. $\varphi$ was evaluated at the tip of nerve fibres reconstructed within the cochlear nerve so as to predict the stimulation of a neuron population. It was found in most cases that a medial electrode array placement produced a narrower $\varphi$ peak at the fibre tip than a lateral one, although the differences were small.

Multiplexed detection of cancer biomarkers using a microfluidic platform integrating single bead trapping and acoustic mixing techniques.

It is critical to reliably and rapidly detect multiple disease biomarkers in tiny liquid samples with high sensitivity to meet the growing demand for point-of-care diagnostics. This paper reports a microfluidic platform integrating magnetic-based single bead trapping in conjunction with acoustic micromixing for simultaneous detection of multiple cancer biomarkers within minutes. Individual beads retained by permalloy (NiFe81/19) microarray were used to capture biomarkers and facilitate the fluorescence identification. A numerical study indicates that the magnetic force keeping a bead in the trap is proportional to the thickness of the permalloy array and the external magnetic field strength, while inversely proportional to the size of the trap. The acoustic microstreaming activated by a piezo transducer was applied to generate fast-switching flow patterns to minimize the diffusion length scales. The flow at various driving frequencies was experimentally tested to achieve the optimal mixing effect. The flow field of the microstreaming was subsequently described by a mathematical model to understand the flow further. Finally, the prostate-specific antigen (PSA) and carcinoembryonic antigen (CEA) were employed as model analytes to demonstrate the capability of the platform for rapid biomarker detection. With the aid of acoustic micromixing, the detection can be finished in 20 minutes. The respective limit of detection of PSA and CEA is 0.028 ng mL-1 (0.8 pM) and 3.1 ng mL-1 (17 pM), which is respectively 1/142 and 1/3 of the cutoff value of PSA and CEA. Our results indicate this platform has great potential for the rapid detection of multiple biomarkers in future point-of-care diagnostics.

Computational Simulation of Tumor Hypoxia Based on In Vivo Microvasculature Assessed in a Dorsal Skin Window Chamber.

Malignant growth usually leads to the depletion of oxygen (O2) supply in most solid tumors. Hypoxia can cause resistance to standard radiotherapy, some chemotherapy and immunotherapy. Furthermore, it can also trigger malignant progression by modulating gene expression and inducing genetic instability. The relationship between microvasculature, perfusion and tumor hypoxia has been intensively studied and many computational simulations have been developed to model tissue O2 transport. Usually simplified 2D phantoms are used to investigate tumor hypoxia and it is assumed that vessels are perpendicular to the region of interest and randomly distributed across the domain. Such idealistic topology overlooks vascular heterogeneity and is not accurate enough to approximate real scenarios. In addition, experimental verification of the spatial gradient of computational simulations is not directly feasible. Realistic vasculature obtained from fluorescence imaging imported as geometry for partial differential equations solving did not receive necessary attention so far. Therefore, we established a computational simulation of in vivo conditions using experimental data obtained from dorsal skin window chamber tumor preparations in nude rats for the verification of computational results. Tumor microvasculature was assessed by fluorescence microscopy. Since the conventional finite difference method can hardly satisfy the real measurements, we established a finite element method (FEM) for the experimental data in this study. Realistic 2D tumor microvasculature was reconstructed by segmenting fluorescence images and then translated into FEM topology. O2 distributions and the O2 gradients were obtained by solving reaction-diffusion equations. The simulation results show that the development of tumor hypoxia is greatly influenced by the irregular architecture and function of microvascular networks.

Concurrent electrical cervicomedullary stimulation and cervical transcutaneous spinal direct current stimulation result in a stimulus interaction.

NEW FINDINGS: What is the central question of this study? We previously showed that the motor pathway is not modified after cervical transcutaneous spinal direct current stimulation (tsDCS) applied using anterior-posterior electrodes. Here, we examine the motor pathway during stimulation. What is the main finding and its importance? We show that electrically elicited muscle responses to cervicomedullary stimulation are modified during tsDCS, whereas magnetically elicited responses are not. Modelling reveals electrical field modifications during concurrent tsDCS and electrical cervicomedullary stimulation. Changes in muscle response probably result from electrical field modifications rather than physiological changes. Care should be taken when applying electrical stimuli simultaneously. Transcutaneous spinal direct current stimulation (tsDCS) can modulate neuronal excitability within the human spinal cord; however, few studies have used tsDCS at a cervical level. This study aimed to characterize cervical tsDCS further by observing its acute effects on motor responses to transcranial magnetic stimulation and cervicomedullary stimulation. In both studies 1 and 2, participants (study 1, n = 8, four female; and study 2, n = 8, three female) received two periods of 10 min, 3 mA cervical tsDCS on the same day through electrodes placed in an anterior-posterior configuration over the neck; one period with the cathode posterior (c-tsDCS) and the other with the anode posterior (a-tsDCS). In study 1, electrically elicited cervicomedullary motor evoked potentials (eCMEPs) and transcranial magnetic stimulation-elicited motor evoked potentials (MEPs) were measured in biceps brachii and flexor carpi radialis before, during and after each tsDCS period. In study 2, eCMEPs and magnetically elicited CMEPs (mCMEPs) were measured before, during and after each tsDCS period. For study 3, computational modelling was used to observe possible interactions of cervical tsDCS and electrical cervicomedullary stimulation. Studies 1 and 2 revealed that eCMEPs were larger during c-tsDCS and smaller during a-tsDCS compared with those elicited when tsDCS was off (P < 0.05), with no changes in MEPs or mCMEPs. Modelling revealed that eCMEP changes might result from modifications of the electrical field direction and magnitude when combined with cervical tsDCS. Bidirectional eCMEP changes are likely to be caused by an interaction between cervical tsDCS and electrical cervicomedullary stimulation; therefore, care should be taken when combining such electrical stimuli in close proximity.

The Effect of Transcranial Direct Current Stimulation (tDCS) Electrode Size and Current Intensity on Motor Cortical Excitability: Evidence From Single and Repeated Sessions.

BACKGROUND: Current density is considered an important factor in determining the outcomes of tDCS, and is determined by the current intensity and electrode size. Previous studies examining the effect of these parameters on motor cortical excitability with small sample sizes reported mixed results. OBJECTIVE/HYPOTHESIS: This study examined the effect of current intensity (1 mA, 2 mA) and electrode size (16 cm(2), 35 cm(2)) on motor cortical excitability over single and repeated tDCS sessions. METHODS: Data from seven studies in 89 healthy participants were pooled for analysis. Single-session data were analyzed using mixed effects models and repeated-session data were analyzed using mixed design analyses of variance. Computational modeling was used to examine the electric field generated. RESULTS: The magnitude of increases in excitability after anodal tDCS was modest. For single-session tDCS, the 35 cm(2) electrodes produced greater increases in cortical excitability compared to the 16 cm(2) electrodes. There were no differences in the magnitude of cortical excitation produced by 1 mA and 2 mA tDCS. The repeated-sessions data also showed that there were greater increases in excitability with the 35 cm(2) electrodes. Further, repeated sessions of tDCS with the 35 cm(2) electrodes resulted in a cumulative increase in cortical excitability. Computational modeling predicted higher electric field at the motor hotspot for the 35 cm(2) electrodes. CONCLUSIONS: 2 mA tDCS does not necessarily produce larger effects than 1 mA tDCS in healthy participants. Careful consideration should be given to the exact positioning, size and orientation of tDCS electrodes relative to cortical regions.

Focalised stimulation using high definition transcranial direct current stimulation (HD-tDCS) to investigate declarative verbal learning and memory functioning.

BACKGROUND: Declarative verbal learning and memory are known to be lateralised to the dominant hemisphere and to be subserved by a network of structures, including those located in frontal and temporal regions. These structures support critical components of verbal memory, including working memory, encoding, and retrieval. Their relative functional importance in facilitating declarative verbal learning and memory, however, remains unclear. OBJECTIVE: To investigate the different functional roles of these structures in subserving declarative verbal learning and memory performance by applying a more focal form of transcranial direct current stimulation, "High Definition tDCS" (HD-tDCS). Additionally, we sought to examine HD-tDCS effects and electrical field intensity distributions using computer modelling. METHODS: HD-tDCS was administered to the left dorsolateral prefrontal cortex (LDLPFC), planum temporale (PT), and left medial temporal lobe (LMTL) to stimulate the hippocampus, during learning on a declarative verbal memory task. Sixteen healthy participants completed a single blind, intra-individual cross-over, sham-controlled study which used a Latin Square experimental design. Cognitive effects on working memory and sustained attention were additionally examined. RESULTS: HD-tDCS to the LDLPFC significantly improved the rate of verbal learning (p=0.03, η(2)=0.29) and speed of responding during working memory performance (p=0.02, η(2)=0.35), but not accuracy (p=0.12, η(2)=0.16). No effect of tDCS on verbal learning, retention, or retrieval was found for stimulation targeted to the LMTL or the PT. Secondary analyses revealed that LMTL stimulation resulted in increased recency (p=0.02, η(2)=0.31) and reduced mid-list learning effects (p=0.01, η(2)=0.39), suggesting an inhibitory effect on learning. CONCLUSIONS: HD-tDCS to the LDLPFC facilitates the rate of verbal learning and improved efficiency of working memory may underlie performance effects. This focal method of administrating tDCS has potential for probing and enhancing cognitive functioning.

Clinical Pilot Study and Computational Modeling of Bitemporal Transcranial Direct Current Stimulation, and Safety of Repeated Courses of Treatment, in Major Depression.

OBJECTIVES: This study aimed to examine a bitemporal (BT) transcranial direct current stimulation (tDCS) electrode montage for the treatment of depression through a clinical pilot study and computational modeling. The safety of repeated courses of stimulation was also examined. METHODS: Four participants with depression who had previously received multiple courses of tDCS received a 4-week course of BT tDCS. Mood and neuropsychological function were assessed. The results were compared with previous courses of tDCS given to the same participants using different electrode montages. Computational modeling examined the electric field maps produced by the different montages. RESULTS: Three participants showed clinical improvement with BT tDCS (mean [SD] improvement, 49.6% [33.7%]). There were no adverse neuropsychological effects. Computational modeling showed that the BT montage activates the anterior cingulate cortices and brainstem, which are deep brain regions that are important for depression. However, a fronto-extracephalic montage stimulated these areas more effectively. No adverse effects were found in participants receiving up to 6 courses of tDCS. CONCLUSIONS: Bitemporal tDCS was safe and led to clinically meaningful efficacy in 3 of 4 participants. However, computational modeling suggests that the BT montage may not activate key brain regions in depression more effectively than another novel montage--fronto-extracephalic tDCS. There is also preliminary evidence to support the safety of up to 6 repeated courses of tDCS.

Revisiting frontoparietal montage in electroconvulsive therapy: clinical observations and computer modeling: a future treatment option for unilateral electroconvulsive therapy.

OBJECTIVES: The aim of this study was to compare the clinical effects of frontoparietal electrode placement, an alternative montage for right unilateral electroconvulsive therapy (ECT), with the commonly used temporoparietal montage. METHODS: In a single patient who received alternate treatments with the abovementioned right unilateral montages, within a treatment course of ECT, time-to-reorientation after each treatment and seizure expression were compared. Computer modeling was used to simulate and compare differences in electrical stimulation patterns in key cerebral regions, with the 2 montages. These simulations were done in an anatomically realistic head model recreated from magnetic resonance imaging scans of the patient's head. RESULTS: Time-to-reorientation was shorter after treatment with frontoparietal ECT (mean, 28.3 minutes; SD, 2.9 minutes) than after temporoparietal ECT (mean, 50.0 minutes; SD, 11.5 minutes), suggesting less retrograde memory impairment. Seizure duration and expression were similar for the 2 montages. Computer modeling demonstrated less hippocampal and right inferior frontal cortical stimulation but comparable anterior cingulate cortex stimulation with the frontoparietal montage. CONCLUSIONS: These results, although preliminary, suggest that the frontoparietal montage may result in less memory side effects, but comparable efficacy, to the temporoparietal montage.

A pilot study of alternative transcranial direct current stimulation electrode montages for the treatment of major depression.

BACKGROUND: Typically, transcranial direct current stimulation (tDCS) treatments for depression have used bifrontal montages with anodal (excitatory) stimulation targeting the left dorsolateral prefrontal cortex (DLPFC). There is limited research examining the effects of alternative electrode montages. OBJECTIVE/HYPOTHESIS: This pilot study aimed to examine the feasibility, tolerability and safety of two alternative electrode montages and provide preliminary data on efficacy. The montages, Fronto-Occipital (F-O) and Fronto-Cerebellar (F-C), were designed respectively to target midline brain structures and the cerebellum. METHODS: The anode was placed over the left supraorbital region and the cathode over the occipital and cerebellar region for the F-O and F-C montages respectively. Computational modelling was used to determine the electric fields produced in the brain regions of interest compared to a standard bifrontal montage. The two montages were evaluated in an open label study of depressed participants (N=14). Mood and neuropsychological functioning were assessed at baseline and after four weeks of tDCS. RESULTS: Computational modelling revealed that the novel montages resulted in greater activation in the anterior cingulate cortices and cerebellum than the bifrontal montage, while activation of the DLPFCs was higher for the bifrontal montage. After four weeks of tDCS, overall mood improvement rates of 43.8% and 15.9% were observed under the F-O and F-C conditions, respectively. No significant neuropsychological changes were found. LIMITATIONS: The clinical pilot was open-label, without a control condition and computational modelling was based on one healthy participant. CONCLUSIONS: Results found both montages safe and feasible. The F-O montage showed promising antidepressant potential.