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Research Interests: Psychology, Bipolar Disorder, Cognition, Attention, Working Memory, and 15 moreTreatment Outcome, Medicine, Multidisciplinary, Prefrontal Cortex, Humans, Cerebellum, Female, Male, Clinical Sciences, Transcranial Direct Current Stimulation, Adult, Bipolar Disorders, Task Performance and Analysis, Neurosciences, and Medical and Health Sciences
Research Interests: Psychology, Depression, Bipolar Disorder, Treatment Outcome, Adolescent, and 15 moreMedicine, Prefrontal Cortex, Mood, Humans, Antidepressant, Female, Male, Young Adult, Transcranial Direct Current Stimulation, Aged, Middle Aged, Brain Stimulation, Adult, Randomized Controlled Trial, and Medical and Health Sciences
BACKGROUND Major depressive disorder (MDD) is commonly associated with neurocognitive dysfunction. However, there remains substantial heterogeneity between patients and inconsistent findings regarding the magnitude and prevalence of... more
BACKGROUND Major depressive disorder (MDD) is commonly associated with neurocognitive dysfunction. However, there remains substantial heterogeneity between patients and inconsistent findings regarding the magnitude and prevalence of specific neurocognitive deficits. This study aimed to investigate the potential for different neurocognitive subgroups in patients diagnosed with MDD. METHOD Data were pooled from 4 different clinical trials that involved adults diagnosed with MDD. Neurocognitive outcomes included measures of verbal learning and memory, executive function, attention, and processing speed. Latent class analysis was conducted to examine for different subgroups based on neurocognitive profiles of performance across outcome measures. Subgroups were compared to a separate sample of age-matched adult healthy controls, across illness factors, and individual mood items on the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS Within the MDD cohort (N = 149), 45% of participants were considered relatively "cognitively preserved," with the remainder "cognitively reduced" (39%) or "cognitively impaired" (16%). Verbal memory performance was significantly poorer compared to attention and processing speed only in the "cognitively impaired" subgroup. There was no association between subgroup membership and relevant illness factors, including ratings on individual MADRS items. LIMITATIONS Data were pooled from several studies that included different neurocognitive measures and cohorts. CONCLUSIONS Approximately half of MDD participants had no or minimal objective cognitive difficulties, and neurocognitive functioning was found generally unrelated to illness factors. Future longitudinal research is warranted to determine whether the people who are relatively cognitively impaired are at increased risk for further cognitive decline. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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Research Interests: Psychology, Dementia, Cognition, Physical Medicine and Rehabilitation, Biological Sciences, and 7 moreBiological Psychiatry, Cognitive training, Transcranial Direct Current Stimulation, Brain Stimulation, Randomized Controlled Trial, Psychology and Cognitive Sciences, and Medical and Health Sciences
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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... more
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. 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. 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. 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. 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.
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Research Interests: Psychology, Transcranial Magnetic Stimulation, Treatment Outcome, Adolescent, Medicine, and 15 moreNeuroplasticity, Affect, Humans, Antidepressant, Female, Male, Ketamine, Neuronal Plasticity, Young Adult, Motor Cortex, Clinical Sciences, Adult, Intranasal Administration, Pilot Projects, and Antidepressive agents
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Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent developments of highly-deployable transcranial electric stimulation (tES)... more
Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent developments of highly-deployable transcranial electric stimulation (tES) systems, combined with mobile-Health technologies, could be incorporated in digital trials to overcome methodological barriers and increase equity of access. We convened 61 highly-productive specialists and contacted 8 tES companies to assess 71 issues related to tES digitalization readiness, and processes, barriers, advantages, and opportunities for implementing tES digital trials. Delphi-based recommendations (>60% agreement) were provided. Device appraisal showed moderate digitalization readiness, with high safety and the possibility of trial implementation, but low connectivity. Panelists recognized the potential of tES for scalability, generalizability, and leverage of digital trials processes; although they reached no consensus about aspects rega...
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Research Interests: Psychology, Neurology, Patient Safety, Transcranial Magnetic Stimulation, Medicine, and 15 moreNon Invasive Brain Stimulation, Infectious Disease, Transcranial Direct Current Stimulation, Brain Stimulation, Transcranial Alternating Current Stimulation, Health Services Administration, Medicine and Health Sciences, Elsevier, Virus diseases, Pandemic, Transcranial Electrical Stimulation, Nervous System Diseases, Psychiatry and Psychology, CoVid, and Medical and Health Sciences
ObjectiveTo examine the clinical outcomes of ECT unilateral placements compared in prior studies and apply insights from computational modelling to understand differences between placements.MethodsPubMed, Embase, Scopus and PsycINFO and... more
ObjectiveTo examine the clinical outcomes of ECT unilateral placements compared in prior studies and apply insights from computational modelling to understand differences between placements.MethodsPubMed, Embase, Scopus and PsycINFO and reference lists were systematically searched for studies of depressed patients where two unilateral placements were compared and clinical outcomes were reported. Computational modelling was done to generate electric field maps for each unilateral placement identified in the systematic review.ResultsA total of 29 studies met criteria for inclusion. Eight studies reported efficacy outcomes and 23 studies reported cognitive outcomes. Most studies found no significant difference in efficacy between right unilateral (RUL) and left unilateral (LUL) ECT, and no difference was found between temporo‐parietal and fronto‐temporal ECT. For the majority of studies, RUL placements had better verbal anterograde memory outcomes compared with the LUL placements. Ther...
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ABSTRACTTranscranial direct current stimulation (tDCS), a form of non-invasive brain stimulation, is a promising treatment for depression. Recent research suggests that tDCS efficacy can be augmented using concurrent cognitive emotional... more
ABSTRACTTranscranial direct current stimulation (tDCS), a form of non-invasive brain stimulation, is a promising treatment for depression. Recent research suggests that tDCS efficacy can be augmented using concurrent cognitive emotional training (CET). However, the neurophysiological changes associated with this combined intervention remain to be elucidated. We therefore examined the effects of tDCS combined with CET using electroencephalography (EEG). A total of 20 participants with treatment resistant depression took part in this open-label study and received 18 sessions over 6 weeks of tDCS and concurrent CET. Resting-state and task-related EEG during a 3-back working memory task were aquired at baseline and immediately following the treatment course. Results showed an improvement in mood and working memory accuracy, but not response time, following the intervention. We did not find significant effects of the intervention on resting-state power spectral density (frontal theta and...
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While the clinical results from transcranial direct current stimulation (tDCS) for the treatment of depression have been promising, antidepressant effects in patients with medication resistance have been suboptimal. There is therefore a... more
While the clinical results from transcranial direct current stimulation (tDCS) for the treatment of depression have been promising, antidepressant effects in patients with medication resistance have been suboptimal. There is therefore a need to further optimise tDCS for medication resistant patients. In this clinical pilot study we examined the feasibility, safety, and clinical efficacy of combining tDCS with a psychological intervention which targets dysfunctional circuitry related to emotion regulation in depression, Cognitive Emotional Training (CET). tDCS was administered during CET three times a week for a total of 18 sessions over 6 weeks. Mood, cognition and emotion processing outcomes were examined at baseline and after 3 and 6 weeks of treatment. Twenty patients with medication resistant depression participated, of whom 17 were study completers. tDCS combined with CET was found to be feasible, safe, and associated with significant antidepressant efficacy at 6 weeks, with 41...
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Background —Unstable angina and non–Q-wave myocardial infarction involve coronary arterial plaque rupture, platelet activation, and thrombus formation. This study tested the benefit of different doses of lamifiban (a platelet IIb/IIIa... more
Background —Unstable angina and non–Q-wave myocardial infarction involve coronary arterial plaque rupture, platelet activation, and thrombus formation. This study tested the benefit of different doses of lamifiban (a platelet IIb/IIIa antagonist) alone and in combination with heparin in patients with these conditions to select the most promising lamifiban regimen for subsequent evaluation. Methods and Results —At 273 hospitals in 20 countries, 2282 patients were randomly assigned to lamifiban (2×2 factorial design: low-dose [1 μg/min] with and without heparin versus high-dose [5 μg/min] with and without heparin) or to standard therapy (placebo and heparin). All patients received aspirin. The composite primary end point of death or nonfatal myocardial infarction at 30 days occurred in 11.7% of those receiving standard therapy, 10.6% receiving low-dose lamifiban, and 12.0% receiving high-dose lamifiban ( P =0.668). By 6 months, this composite was lowest for those assigned to low-dose ...
Research Interests: Medicine, Platelet, Internal Medicine, Heparin, Aspirin, and 12 moreClinical Sciences, Myocardial Infarction, Public health systems and services research, Randomized Controlled Trial, Circulation, Medicine and Health Sciences, Angina, Regimen, Unstable Angina, Tirofiban, Medical and Health Sciences, and Cardiovascular medicine and haematology
Background Transcranial electrical stimulation has broad potential as a treatment for depression. Transcranial random noise stimulation (tRNS), which delivers randomly fluctuating current intensities, may have greater cortical excitatory... more
Background Transcranial electrical stimulation has broad potential as a treatment for depression. Transcranial random noise stimulation (tRNS), which delivers randomly fluctuating current intensities, may have greater cortical excitatory effects compared to other forms of transcranial electrical stimulation. We therefore aimed to investigate the antidepressant efficacy of tRNS. Methods Depressed participants were randomly assigned by computer number generator to receive 20 sessions of either active or sham tRNS over four weeks in a double-blinded, parallel group randomized-controlled trial. tRNS was delivered for 30mins with a direct current offset of 2mA and a random noise range of 2mA. Primary analyses assessed changes in depression severity using the Montgomery-Asperg Depression Rating Scale (MADRS). Neuroplasticity, neuropsychological, and safety outcomes were analysed as secondary measures. Results 69 participants were randomised, of which three discontinued treatment early lea...
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BackgroundReduction of the pulse width has been reported to improve ECT outcomes with unilateral ECT (similar efficacy, fewer cognitive side effects), but has been minimally studied for bitemporal ECT. The only study comparing brief and... more
BackgroundReduction of the pulse width has been reported to improve ECT outcomes with unilateral ECT (similar efficacy, fewer cognitive side effects), but has been minimally studied for bitemporal ECT. The only study comparing brief and ultrabrief pulse bitemporal ECT found reduced efficacy for bitemporal ultrabrief compared to bitemporal brief pulse stimulation. This randomised controlled trial (RCT) aimed to test if ultrabrief pulse bitemporal ECT results in fewer cognitive side effects than brief pulse bitemporal ECT, when given at doses adjusted with the aim of achieving comparable efficacy.MethodsThirty-six participants were randomly assigned to receive ultrabrief (at 3 times seizure threshold) or brief (at 1.5 times seizure threshold) pulse bitemporal ECT given 3 times a week in a double-blind, controlled proof-of-concept trial. Blinded raters assessed mood and cognitive functioning over the ECT course.ResultsEfficacy and cognitive outcomes did not differ significantly between...
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The anesthetic-electroconvulsive therapy (ECT) time interval (time interval elapsed from the beginning of anesthesia injection to the beginning of ECT stimulus) has been reported to have an important impact on seizure quality outcomes,... more
The anesthetic-electroconvulsive therapy (ECT) time interval (time interval elapsed from the beginning of anesthesia injection to the beginning of ECT stimulus) has been reported to have an important impact on seizure quality outcomes, because it is an indirect measure of the anesthetic plasma concentration when the ECT electrical stimulus is administered. We report the importance of the routine monitoring of this time interval in clinical settings, as an additional measure to interpret seizure quality outcomes at each ECT session, to further assist on ECT dosing decisions during the treatment course.
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There is currently substantial heterogeneity in electroconvulsive therapy (ECT) treatment methods between clinical settings. Understanding how this variation in clinical practice is related to treatment outcomes is essential for... more
There is currently substantial heterogeneity in electroconvulsive therapy (ECT) treatment methods between clinical settings. Understanding how this variation in clinical practice is related to treatment outcomes is essential for optimizing service delivery. The Clinical Alliance and Research in ECT Network is a clinical and research framework with the aims of improving clinical practice, enabling auditing and benchmarking, and facilitating the collection of naturalistic clinical data. The network framework and clinical and treatment variables collected and rationale for the use of particular outcome measures are described. Survey results detailing the use of ECT across initial participating clinical centers were examined. The data are reported from 18 of 22 participating centers, the majority based in Australia. Melancholic unipolar depression was the most common clinical indication (78%). Right unilateral (44%) and bifrontal (39%) were the most commonly used electrode placements. E...
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Electroconvulsive therapy (ECT) is an effective and widely used treatment for major depressive disorder, in which a brief electric current is passed through the brain to trigger a brief seizure. This study aims to identify seizure quality... more
Electroconvulsive therapy (ECT) is an effective and widely used treatment for major depressive disorder, in which a brief electric current is passed through the brain to trigger a brief seizure. This study aims to identify seizure quality rating by utilizing a set of seizure parameters. We used 750 ECT EEG recordings in this experiment. Four seizure related parameters, (time of slowing, regularity, stereotypy and post-ictal suppression) are used as inputs to two classifiers, decision tree and fuzzy inference system (FIS), to predict seizure quality ratings. The two classifiers produced encouraging results with error rate of 0.31 and 0.25 for FIS and decision tree, respectively. The classification results show that the four seizure parameters provide relevant information about the rating of seizure quality. Automatic scoring of seizure quality may be beneficial to clinicians working in this field.
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BackgroundExtensive clinical research has shown that the efficacy and cognitive outcomes of electroconvulsive therapy (ECT) are determined, in part, by the type of electrode placement used. Bitemporal ECT (BT, stimulating electrodes... more
BackgroundExtensive clinical research has shown that the efficacy and cognitive outcomes of electroconvulsive therapy (ECT) are determined, in part, by the type of electrode placement used. Bitemporal ECT (BT, stimulating electrodes placed bilaterally in the frontotemporal region) is the form of ECT with relatively potent clinical and cognitive side effects. However, the reasons for this are poorly understood.ObjectiveThis study used computational modelling to examine regional differences in brain excitation between BT, Bifrontal (BF) and Right Unilateral (RUL) ECT, currently the most clinically-used ECT placements. Specifically, by comparing similarities and differences in current distribution patterns between BT ECT and the other two placements, the study aimed to create an explanatory model of critical brain sites that mediate antidepressant efficacy and sites associated with cognitive, particularly memory, adverse effects.MethodsHigh resolution finite element human head models w...
Research Interests: Psychology, Deep Brain Stimulation, Cognition, Magnetic Resonance Imaging, Treatment Outcome, and 11 moreMedicine, Finite Element Analysis, Electroconvulsive therapy, Temporal Lobe, Humans, Computer Simulation, Frontal Lobe, Cognitive dysfunction, Psychology and Cognitive Sciences, european psychiatry, and Medical and Health Sciences
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To assess the efficacy and safety of subcutaneous ketamine for geriatric treatment-resistant depression. Secondary aims were to examine if repeated treatments were safe and more effective in inducing or prolonging remission than a single... more
To assess the efficacy and safety of subcutaneous ketamine for geriatric treatment-resistant depression. Secondary aims were to examine if repeated treatments were safe and more effective in inducing or prolonging remission than a single treatment. In this double-blind, controlled, multiple-crossover study with a 6-month follow-up (randomized controlled trial [RCT] phase), 16 participants (≥60 years) with treatment-resistant depression who relapsed after remission or did not remit in the RCT were administered an open-label phase. Up to five subcutaneous doses of ketamine (0.1, 0.2, 0.3, 0.4, and 0.5 mg/kg) were administered in separate sessions (≥1 week apart), with one active control (midazolam) randomly inserted (RCT phase). Twelve ketamine treatments were given in the open-label phase. Mood, hemodynamic, and psychotomimetic outcomes were assessed by blinded raters. Remitters in each phase were followed for 6 months. Seven of 14 RCT-phase completers remitted with ketamine treatmen...
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Research Interests: Psychology, Cognitive Psychology, Computer Science, Attention, Medicine, and 15 morePrefrontal Cortex, Non Invasive Brain Stimulation, Learning, Memory, Hippocampus, Temporal Lobe, Brain, Humans, Female, Neuroimage, Male, Adult, Short Term Memory, Psychology and Cognitive Sciences, and Medical and Health Sciences
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... more
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. 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. 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-...
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White matter in the brain exhibits strong anisotropic conductivity. Modeling studies on electroencephalography have found that such anisotropic conductivity greatly influences the estimated dipole source. In this study, we made a detailed... more
White matter in the brain exhibits strong anisotropic conductivity. Modeling studies on electroencephalography have found that such anisotropic conductivity greatly influences the estimated dipole source. In this study, we made a detailed comparison of the effects of conductivity anisotropy using a computational model of electroconvulsive therapy (ECT). The human head model was a high resolution finite element model generated from MRI scans, implemented with tissue heterogeneity and an excitable neural model incorporated in the brain. Results showed that anisotropy in conductivity had minimal effects on the location of the brain region that was maximally activated, but it had relatively large effects on deep brain structures.
Research Interests: Computer Science, Materials Science, Medicine, Anisotropy, Electroconvulsive therapy, and 14 moreBrain, Humans, Computer Simulation, Computer Model, Dipole, Conductivity, High Resolution, White matter, Finite Element Model, Fractional Anisotropy, Brain Structure, Biological System Modeling, Action Potentials, and Neural Network Model
Electroconvulsive therapy (ECT) is a highly effective treatment for severe depressive disorder. Efficacy and cognitive outcomes have been shown to depend on variations in treatment technique. A high resolution finite element model of a... more
Electroconvulsive therapy (ECT) is a highly effective treatment for severe depressive disorder. Efficacy and cognitive outcomes have been shown to depend on variations in treatment technique. A high resolution finite element model of a human head was generated from MRI scans and implemented with tissue heterogeneity and an excitable ionic neural model incorporated in the brain. The model was used to compare the effects of three common ECT electrode configurations, including the spatial profiles of electric field and excitation in the brain. The results showed that electrode placement has a significant effect in determining the spatial extent of activation in different brain regions, which would account for differences seen in clinical outcomes.