ORCID Profile
0000-0003-1291-4304
Current Organisations
University of Minnesota
,
Deakin University
,
Mayo Clinic Rochester
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Behavioural neuroscience | Biological psychology | Central nervous system | Decision making
ANZSRC Socio-Economic Objective (SEO)
Related Links
Publications
Informing Brain Health Behaviour Choices: The Efficacy of a High-School Brain Awareness Pilot Study
Publisher: Sciencedomain International
Date: 10-01-2014
How Well Do We Understand the Long-Term Health Implications of Childhood Bullying?
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2017
DOI: 10.1097/HRP.0000000000000137
Abstract: Once dismissed as an innocuous experience of childhood, bullying is now recognized as having significant psychological effects, particularly with chronic exposure. Victims of bullying are at risk for a number of psychiatric disturbances, and growing evidence suggests that the pathophysiological effects of bullying, as with other forms of trauma and chronic stress, create additional health risks. We review the literature on the known sequelae of bullying, including psychiatric and physiological health effects, with a focus on implications for the victim. In addition, since it is now well established that early and chronic exposure to stress has a significant negative impact on health outcomes, we explore the implications of this research in relation to bullying and victimization in childhood. In particular, we examine how aspects of the stress response, via epigenetic, inflammatory, and metabolic mediators, have the capacity to compromise mental and physical health, and to increase the risk of disease. Research on the relevant mechanisms associated with bullying and on potential interventions to decrease morbidity is urgently needed.
Fostering Resilience among Mothers under Stress: “Authentic Connections Groups” for Medical Professionals
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1016/J.WHI.2017.02.007
Abstract: We report on effects of an intervention to foster resilience among professional women at high risk for stress and burnout: health care providers (physicians, PhD clinicians, physician assistants, and nurse practitioners) who are mothers. Between February and November 2015, 40 mothers on staff at the Mayo Clinic, Arizona, were assigned randomly to either 1) 12 weekly 1-hour sessions of a structured, relational supportive intervention, the Authentic Connections Groups (n = 21) with protected time to attend sessions or to 2) 12 weekly hours of protected time to be used as desired (controls n = 19). Participants were assessed at baseline, after the intervention, and 3 months follow-up on multiple psychological measures plus plasma cortisol. Across the 12 weeks of the intervention groups, there were zero dropouts. After the intervention, analyses of covariance showed significantly greater improvements (p < .05) for mothers in the Authentic Connections Groups than control condition for depression and global symptoms. By 3 months follow-up, significant differences were seen for these two dimensions and almost all other central variables, including self-compassion, feeling loved, physical affection received, and parenting stress, with moderate effect sizes (η Facilitated colleague support groups could be a viable, low-cost, preventive intervention to mitigate burnout and distress for mothers in high-stress professional settings such as hospitals, resulting in personal benefit, greater engagement at work, and attenuated stress associated with parenting.
Multi-layer implantable antenna for closed loop deep brain stimulation system
Publisher: IEEE
Date: 10-2012
Design and analysis of an antenna for wireless energy harvesting in a head-mountable DBS device
Publisher: IEEE
Date: 07-2013
A miniature closed-loop deep brain stimulation device
Publisher: IEEE
Date: 08-2016
Deep brain stimulation for treatment-resistant depression: Efficacy, safety and mechanisms of action
Publisher: Elsevier BV
Date: 09-2012
DOI: 10.1016/J.NEUBIOREV.2012.06.001
Abstract: Deep brain stimulation (DBS), a neuromodulation therapy that has been used successfully in the treatment of symptoms associated with movement disorders, has recently undergone clinical trials for in iduals suffering from treatment-resistant depression (TRD). Although the small patient numbers and open label study design limit our ability to identify optimum targets and make definitive conclusions about treatment efficacy, a review of the published research demonstrates significant reductions in depressive symptomatology and high rates of remission in a severely treatment-resistant patient group. Despite these encouraging results, an incomplete understanding of the mechanisms of action underlying the therapeutic effects of DBS for TRD is highlighted, paralleling the incomplete understanding of the neuroanatomy of mood regulation and treatment resistance. Proposed mechanisms of action include short and long-term local effects of stimulation at the neuronal level, to modulation of neural network activity.
Ventral tegmental ionotropic glutamate receptor stimulation of nucleus accumbens tonic dopamine efflux blunts hindbrain-evoked phasic neurotransmission: Implications for dopamine dysregulation disorde
Publisher: Elsevier BV
Date: 11-2013
DOI: 10.1016/J.NEUROSCIENCE.2013.08.010
Abstract: Activation of glutamate receptors within the ventral tegmental area (VTA) stimulates extrasynaptic (basal) dopamine release in terminal regions, including the nucleus accumbens (NAc). Hindbrain inputs from the laterodorsal tegmental nucleus (LDT) are critical for elicitation of phasic VTA dopamine cell activity and consequent transient dopamine release. This study investigated the role of VTA ionotropic glutamate receptor (iGluR) stimulation on both basal and LDT electrical stimulation-evoked dopamine efflux in the NAc using in vivo chrono erometry and fixed potential erometry in combination with stearate-graphite paste and carbon fiber electrodes, respectively. Intra-VTA infusion of the iGluR agonists (±)-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA 1 μg/μl) or N-methyl-d-aspartic acid (NMDA 2 μg/μl) enhanced basal NAc dopamine efflux. This iGluR-mediated potentiation of basal dopamine efflux was paralleled by an attenuation of LDT-evoked transient NAc dopamine efflux, suggesting that excitation of basal activity effectively inhibited the capacity of hindbrain afferents to elicit transient dopamine efflux. In line with this, post-NMDA infusion of the dopamine D2 autoreceptor (D2R) agonist quinpirole (1 μg/μl intra-VTA) partially recovered NMDA-mediated attenuation of LDT-evoked NAc dopamine, while concurrently attenuating NMDA-mediated potentiation of basal dopamine efflux. Post-NMDA infusion of quinpirole (1 μg/μl) alone attenuated basal and LDT-evoked dopamine efflux. Taken together, these data reveal that hyperstimulation of basal dopamine transmission can stunt hindbrain burst-like stimulation-evoked dopamine efflux. Inhibitory autoreceptor mechanisms within the VTA help to partially recover the magnitude of phasic dopamine efflux, highlighting the importance of both iGluRs and D2 autoreceptors in maintaining the functional balance of tonic and phasic dopamine neurotransmission. Dysregulation of this balance may have important implications for disorders of dopamine dysregulation such as attention deficit hyperactivity disorder.
RF rectifiers for EM power harvesting in a Deep Brain Stimulating device
Publisher: Springer Science and Business Media LLC
Date: 20-01-2015
DOI: 10.1007/S13246-015-0328-7
Abstract: A passive deep brain stimulation (DBS) device can be equipped with a rectenna, consisting of an antenna and a rectifier, to harvest energy from electromagnetic fields for its operation. This paper presents optimization of radio frequency rectifier circuits for wireless energy harvesting in a passive head-mountable DBS device. The aim is to achieve a compact size, high conversion efficiency, and high output voltage rectifier. Four different rectifiers based on the Delon doubler, Greinacher voltage tripler, Delon voltage quadrupler, and 2-stage charge pumped architectures are designed, simulated, fabricated, and evaluated. The design and simulation are conducted using Agilent Genesys at operating frequency of 915 MHz. A dielectric substrate of FR-4 with thickness of 1.6 mm, and surface mount devices (SMD) components are used to fabricate the designed rectifiers. The performance of the fabricated rectifiers is evaluated using a 915 MHz radio frequency (RF) energy source. The maximum measured conversion efficiency of the Delon doubler, Greinacher tripler, Delon quadrupler, and 2-stage charge pumped rectifiers are 78, 75, 73, and 76 % at -5 dBm input power and for load resistances of 5-15 kΩ. The conversion efficiency of the rectifiers decreases significantly with the increase in the input power level. The Delon doubler rectifier provides the highest efficiency at both -5 and 5 dBm input power levels, whereas the Delon quadrupler rectifier gives the lowest efficiency for the same inputs. By considering both efficiency and DC output voltage, the charge pump rectifier outperforms the other three rectifiers. Accordingly, the optimised 2-stage charge pumped rectifier is used together with an antenna to harvest energy in our DBS device.
Statistical Modelling of Artificial Neural Network for Sorting Temporally Synchronous Spikes
Publisher: Springer International Publishing
Date: 2015
Corrigendum to “Continuation phase intravenous ketamine in adults with treatment-resistant depression” [J. Affect. Disord. 206 (2016) 300–304](S0165032716313519)(10.1016/j.jad.2016.09.008)
Publisher: Elsevier BV
Date: 08-2018
Lithium augmentation of ketamine increases insulin signaling and antidepressant-like active stress coping in a rodent model of treatment-resistant depression
Publisher: Springer Science and Business Media LLC
Date: 25-11-2021
DOI: 10.1038/S41398-021-01716-W
Abstract: Lithium, a mood stabilizer and common adjunctive treatment for refractory depression, shares overlapping mechanisms of action with ketamine and enhances the duration of ketamine’s antidepressant actions in rodent models at sub-therapeutic doses. Yet, in a recent clinical trial, lithium co-treatment with ketamine failed to improve antidepressant outcomes in subjects previously shown to respond to ketamine alone. The potential for lithium augmentation to improve antidepressant outcomes in ketamine nonresponders, however, has not been explored. The current study examined the behavioral, molecular and metabolic actions of lithium and ketamine co-treatment in a rodent model of antidepressant resistance. Male Wistar rats were administered adrenocorticotropic hormone (ACTH 100 µg/day, i.p. over 14 days) and subsequently treated with ketamine (10 mg/kg 2 days n = 12), lithium (37 mg/kg 2 days n = 12), ketamine + lithium (10 mg/kg + 37 mg/kg 2 days n = 12), or vehicle saline (0.9% n = 12). Rats were subjected to open field (6 min) and forced swim tests (6 min). Peripheral blood and brain prefrontal cortical (PFC) tissue was collected one hour following stress exposure. Western blotting was used to determine the effects of treatment on extracellular signal-regulated kinase (ERK) mammalian target of rapamycin (mTOR), phospho kinase B (Akt), and glycogen synthase kinase-3ß (GSK3ß) protein levels in the infralimbic (IL) and prelimbic (PL) subregions of the PFC. Prefrontal oxygen consumption rate (OCR) and extracellular acidification rates (ECAR) were also determined in anterior PFC tissue at rest and following stimulation with brain-derived neurotrophic factor (BDNF) and tumor necrosis factor α (TNFα). Blood plasma levels of mTOR and insulin were determined using enzyme-linked immunosorbent assays (ELISAs). Overall, rats receiving ketamine+lithium displayed a robust antidepressant response to the combined treatment as demonstrated through significant reductions in immobility time ( p 0.05) and latency to immobility ( p 0.01). These animals also had higher expression of plasma mTOR ( p 0.01) and insulin ( p 0.001). Tissue bioenergetics analyses revealed that combined ketamine+lithium treatment did not significantly alter the respiratory response to BDNF or TNFα. Animals receiving both ketamine and lithium had significantly higher phosphorylation ( p )-to-total expression ratios of mTOR ( p 0.001) and Akt ( p 0.01), and lower ERK in the IL compared to control animals. In contrast, p mTOR/mTOR levels were reduced in the PL of ketamine+lithium treated animals, while p ERK/ERK expression levels were elevated. Taken together, these data demonstrate that lithium augmentation of ketamine in antidepressant nonresponsive animals improves antidepressant-like behavioral responses under stress, together with peripheral insulin efflux and region-specific PFC insulin signaling.
Bioenergetics and synaptic plasticity as potential targets for individualizing treatment for depression
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.NEUBIOREV.2018.04.002
Abstract: Disruptions of bioenergetic signaling and neurogenesis are hallmarks of depression physiology and are often the product of dysregulation of the inflammatory, stress-response, and metabolic systems. These systems are extensively interrelated at the physiological level, yet the bulk of the literature to date addresses pathophysiological mechanisms in isolation. A more integrated understanding of the etiology, progression, and treatment response profiles of depression is possible through wider consideration of relevant preclinical and clinical studies that examine the result of disruptions in these systems. Here, we review recent data demonstrating the critical effects of bioenergetic disruption on neuroplasticity and the development and progression of depressive illness. We further highlight the interactive and dynamic nature of the inflammatory and stress response systems and how disruption of these systems influences bioenergetic signaling pathways critical to treatment outcomes. In so doing, we underscore the pressing need to reconsider the implications of treatment resistance and present a framework for developing novel, personalized treatment approaches for depression.
Wireless Instantaneous Neurotransmitter Concentration System: electrochemical monitoring of serotonin using fast-scan cyclic voltammetry—a proof-of-principle study
Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
Date: 09-2010
Abstract: The authors previously reported the development of the Wireless Instantaneous Neurotransmitter Concentration System (WINCS) for measuring dopamine and suggested that this technology may be useful for evaluating deep brain stimulation–related neuromodulatory effects on neurotransmitter systems. The WINCS supports fast-scan cyclic voltammetry (FSCV) at a carbon-fiber microelectrode (CFM) for real-time, spatially resolved neurotransmitter measurements. The FSCV parameters used to establish WINCS dopamine measurements are not suitable for serotonin, a neurotransmitter implicated in depression, because they lead to CFM fouling and a loss of sensitivity. Here, the authors incorporate into WINCS a previously described N-shaped waveform applied at a high scan rate to establish wireless serotonin monitoring. Optimized for the detection of serotonin, FSCV consisted of an N-shaped waveform scanned linearly from a resting potential of +0.2 to +1.0 V, then to −0.1 V and back to +0.2 V, at a rate of 1000 V/second. Proof-of-principle tests included flow injection analysis and electrically evoked serotonin release in the dorsal raphe nucleus of rat brain slices. Flow cell injection analysis demonstrated that the N waveform, applied at a scan rate of 1000 V/second, significantly reduced serotonin fouling of the CFM, relative to that observed with FSCV parameters for dopamine. In brain slices, WINCS reliably detected subsecond serotonin release in the dorsal raphe nucleus evoked by local high-frequency stimulation. The authors found that WINCS supported high-fidelity wireless serotonin monitoring by FSCV at a CFM. In the future such measurements of serotonin in large animal models and in humans may help to establish the mechanism of deep brain stimulation for psychiatric disease.
Wireless Instantaneous Neurotransmitter Concentration System–based amperometric detection of dopamine, adenosine, and glutamate for intraoperative neurochemical monitoring
Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
Date: 10-2009
Abstract: In a companion study, the authors describe the development of a new instrument named the Wireless Instantaneous Neurotransmitter Concentration System (WINCS), which couples digital telemetry with fast-scan cyclic voltammetry (FSCV) to measure extracellular concentrations of dopamine. In the present study, the authors describe the extended capability of the WINCS to use fixed potential erometry (FPA) to measure extracellular concentrations of dopamine, as well as glutamate and adenosine. Compared with other electrochemical techniques such as FSCV or high-speed chrono erometry, FPA offers superior temporal resolution and, in combination with enzyme-linked biosensors, the potential to monitor nonelectroactive analytes in real time. The WINCS design incorporated a transimpedance lifier with associated analog circuitry for FPA a microprocessor a Bluetooth transceiver and a single, battery-powered, multilayer, printed circuit board. The WINCS was tested with 3 distinct recording electrodes: 1) a carbon-fiber microelectrode (CFM) to measure dopamine 2) a glutamate oxidase enzyme–linked electrode to measure glutamate and 3) a multiple enzyme–linked electrode (adenosine deaminase, nucleoside phosphorylase, and xanthine oxidase) to measure adenosine. Proof-of-principle analyses included noise assessments and in vitro and in vivo measurements that were compared with similar analyses by using a commercial hardwired electrochemical system (EA161 Picostat, eDAQ Pty Ltd). In urethane-anesthetized rats, dopamine release was monitored in the striatum following deep brain stimulation (DBS) of ascending dopaminergic fibers in the medial forebrain bundle (MFB). In separate rat experiments, DBS-evoked adenosine release was monitored in the ventrolateral thalamus. To test the WINCS in an operating room setting resembling human neurosurgery, cortical glutamate release in response to motor cortex stimulation (MCS) was monitored using a large-mammal animal model, the pig. The WINCS, which is designed in compliance with FDA-recognized consensus standards for medical electrical device safety, successfully measured dopamine, glutamate, and adenosine, both in vitro and in vivo. The WINCS detected striatal dopamine release at the implanted CFM during DBS of the MFB. The DBS-evoked adenosine release in the rat thalamus and MCS-evoked glutamate release in the pig cortex were also successfully measured. Overall, in vitro and in vivo testing demonstrated signals comparable to a commercial hardwired electrochemical system for FPA. By incorporating FPA, the chemical repertoire of WINCS-measurable neurotransmitters is expanded to include glutamate and other nonelectroactive species for which the evolving field of enzyme-linked biosensors exists. Because many neurotransmitters are not electrochemically active, FPA in combination with enzyme-linked microelectrodes represents a powerful intraoperative tool for rapid and selective neurochemical s ling in important anatomical targets during functional neurosurgery.
Peripheral proinflammatory markers associated with ketamine response in a preclinical model of antidepressant-resistance
Publisher: Elsevier BV
Date: 10-2015
DOI: 10.1016/J.BBR.2015.07.026
Abstract: Ketamine, N-methyl-d-aspartate (NMDA) receptor antagonist and anti-inflammatory agent, has rapid therapeutic effects in a subset of patients with more intractable forms of depression. Irregular proinflammatory cytokine and acute-reactive protein levels have been reported in clinical and preclinical depression research. We explored the association between the rapid antidepressant-like effects of ketamine and peripheral proinflammatory profile in a model of antidepressant-resistance. Male Wistar rats were pre-treated with ACTH-(1-24) 100μg/d or saline (0.9%) for 14d. Antidepressant-like effects were assessed with the forced swim test (FST). Ketamine (10mg/kg) significantly reduced immobility duration in saline-pretreated control animals. In contrast, a ergent response was observed in ACTH-pretreated antidepressant resistant animals, with 50% responders and 50% non-responders. Plasma s les were analyzed via enzyme-linked immunosorbent assay (ELISA) for interleukin 6 (IL-6), tumour necrosis factor alpha (TNFα) and C-reactive protein (CRP). Levels of CRP and TNFα differentiated ketamine responders and non-responders.
Compact stacked planar inverted-F antenna for passive deep brain stimulation implants
Publisher: IEEE
Date: 08-2012
Towards a classification of biomarkers of neuropsychiatric disease: from encompass to compass
Publisher: Springer Science and Business Media LLC
Date: 28-10-2014
DOI: 10.1038/MP.2014.139
Abstract: There is currently considerable imprecision in the nosology of biomarkers used in the study of neuropsychiatric disease. The neuropsychiatric field lags behind others such as oncology, wherein, rather than using 'biomarker' as a blanket term for a erse range of clinical phenomena, biomarkers have been actively classified into separate categories, including prognostic and predictive tests. A similar taxonomy is proposed for neuropsychiatric diseases in which the core biology remains relatively unknown. This paper ides potential biomarkers into those of (1) risk, (2) diagnosis/trait, (3) state or acuity, (4) stage, (5) treatment response and (6) prognosis, and provides illustrative exemplars. Of course, biomarkers rely on available technology and, as we learn more about the neurobiological correlates of neuropsychiatric disorders, we will realize that the classification of biomarkers across these six categories can change, and some markers may fit into more than one category.
Correction to: Intravenous Ketamine for Adolescents with Treatment-Resistant Depression: An Open-Label Study, by Cullen KR, Amatya P, Roback MG, Albott CS, Westlund Schreiner M, Ren Y, Eberly L
Publisher: Mary Ann Liebert Inc
Date: 02-2019
Unified selective sorting approach to analyse multi-electrode extracellular data
Publisher: Springer Science and Business Media LLC
Date: 24-06-2016
DOI: 10.1038/SREP28533
Abstract: Extracellular data analysis has become a quintessential method for understanding the neurophysiological responses to stimuli. This demands stringent techniques owing to the complicated nature of the recording environment. In this paper, we highlight the challenges in extracellular multi-electrode recording and data analysis as well as the limitations pertaining to some of the currently employed methodologies. To address some of the challenges, we present a unified algorithm in the form of selective sorting. Selective sorting is modelled around hypothesized generative model, which addresses the natural phenomena of spikes triggered by an intricate neuronal population. The algorithm incorporates Cepstrum of Bispectrum, ad hoc clustering algorithms, wavelet transforms, least square and correlation concepts which strategically tailors a sequence to characterize and form distinctive clusters. Additionally, we demonstrate the influence of noise modelled wavelets to sort overlapping spikes. The algorithm is evaluated using both raw and synthesized data sets with different levels of complexity and the performances are tabulated for comparison using widely accepted qualitative and quantitative indicators.
Concomitant benzodiazepine use attenuates ketamine response: implications for large scale study design and clinical development.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2015
501. Epigenetic Modifications of Stress-Relevant Genes as Peripheral Biomarkers of Treatment-Resistant Depression
Publisher: Elsevier BV
Date: 05-2017
Favorable Impact on Stress-Related Behaviors by Modulating Plasma Butyrylcholinesterase
Publisher: Springer Science and Business Media LLC
Date: 15-07-2018
Chronic adrenocorticotrophic hormone treatment alters tricyclic antidepressant efficacy and prefrontal monoamine tissue levels
Publisher: Elsevier BV
Date: 04-2013
DOI: 10.1016/J.BBR.2012.12.033
Abstract: Several animal models are currently utilised in the investigation of major depressive disorder however, each is validated by its response to antidepressant pharmacotherapy. Few animal models consider the notion of antidepressant treatment resistance. Chronic daily administration of adrenocorticotropic hormone (ACTH) or corticosterone can alter behavioural responses to antidepressants, effectively blocking antidepressant efficacy. Herein, we demonstrate that ACTH-(1-24) (100μg/day 14 days) blocks the immobility-reducing 'antidepressant' effects of a single dose of imipramine (10mg/kg) in the forced swim test. This finding was accompanied by altered monoamine tissue levels in the prefrontal cortex (PFC) 1h after exposure to the acute stress of the forced swim test. PFC tissue from ACTH pre-treated animals contained significantly higher serotonin, noradrenaline and adrenaline concentrations relative to saline pre-treated controls. Conversely, dopamine levels were significantly decreased. Altered plasma corticosterone responses to ACTH injections were observed over the treatment course. Measures were taken on treatment days 1, 4, 8, 11, 14 and 15. ACTH administration initially enhanced plasma corticosterone levels, however, these normalised to levels consistent with control animals by day 14. No differences in corticosterone levels were observed across the treatment time course in saline-treated animals. Taken together these results indicate that pre-treatment with ACTH (100μg/day 14 days) blocks the antidepressant effects of imipramine (10mg/kg), significantly alters key PFC monoamine responses to stress and downregulates glucocorticoid responses. These results suggest that chronic ACTH treatment is a promising paradigm for elucidation of mechanisms mediating antidepressant treatment resistance.
Proteasome system dysregulation and treatment resistance mechanisms in major depressive disorder
Publisher: Springer Science and Business Media LLC
Date: 12-2015
DOI: 10.1038/TP.2015.180
Abstract: Several studies have demonstrated that allelic variants related to inflammation and the immune system may increase the risk for major depressive disorder (MDD) and reduce patient responsiveness to antidepressant treatment. Proteasomes are fundamental complexes that contribute to the regulation of T-cell function. Only one study has shown a putative role of proteasomal PSMA7 , PSMD9 and PSMD13 genes in the susceptibility to an antidepressant response, and sparse data are available regarding the potential alterations in proteasome expression in psychiatric disorders such as MDD. The aim of this study was to clarify the role of these genes in the mechanisms underlying the response/resistance to MDD treatment. We performed a case-control association study on 621 MDD patients, of whom 390 were classified as treatment-resistant depression (TRD), and we collected peripheral blood cells and fibroblasts for mRNA expression analyses. The analyses showed that subjects carrying the homozygous GG genotype of PSMD13 rs3817629 had a twofold greater risk of developing TRD and exhibited a lower PSMD13 mRNA level in fibroblasts than subjects carrying the A allele. In addition, we found a positive association between PSMD9 rs1043307 and the presence of anxiety disorders in comorbidity with MDD, although this result was not significant following correction for multiple comparisons. In conclusion, by confirming the involvement of PSMD13 in the MDD treatment response, our data corroborate the hypothesis that the dysregulation of the complex responsible for the degradation of intracellular proteins and potentially controlling autoimmunity- and immune tolerance–related processes may be involved in several phenotypes, including the TRD.
A review of brain insulin signaling in mood disorders: From biomarker to clinical target
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.NEUBIOREV.2018.05.014
Abstract: Patients with mood disorders are at increased risk for metabolic dysfunction. Co-occurrence of the two conditions is typically associated with a more severe disease course and poorer treatment outcomes. The specific pathophysiological mechanisms underlying this bidirectional relationship between mood and metabolic dysfunction remains poorly understood. However, it is likely that impairment of metabolic processes within the brain play a critical role. The insulin signaling pathway mediates metabolic homeostasis and is important in the regulation of neurotrophic and synaptic plasticity processes, including those involved in neurodegenerative diseases like Alzheimer's. Thus, insulin signaling in the brain may serve to link metabolic function and mood. Central insulin signaling is mediated through locally secreted insulin and widespread insulin receptor expression. Here we review the preclinical and clinical data addressing the relationships between central insulin signaling, cellular metabolism, neurotrophic processes, and mood regulation, including key points of mechanistic overlap. These relationships have important implications for developing biomarker-based diagnostics and precision medicine approaches to treat severe mood disorders.
Towards miniaturized closed-loop optogenetic stimulation devices
Publisher: IOP Publishing
Date: 24-01-2018
Abstract: Electrical brain stimulation provides therapeutic benefits for patients with drug-resistant neurological disorders. It, however, has restricted access to cell-type selectivity which limits its treatment effectiveness. Optogenetics, in contrast, enables precise targeting of a specific cell type which can address the issue with electrical brain stimulation. It, nonetheless, disregards real-time brain responses in delivering optimized stimulation to target cells. Closed-loop optogenetics, on the other hand, senses the difference between normal and abnormal states of the brain, and modulates stimulation parameters to achieve the desired stimulation outcome. Current review articles on closed-loop optogenetics have focused on its theoretical aspects and potential benefits. A review of the recent progress in miniaturized closed-loop optogenetic stimulation devices is thus needed. This paper presents a comprehensive study on the existing miniaturized closed-loop optogenetic stimulation devices and their internal components. Hardware components of closed-loop optogenetic stimulation devices including electrode, light-guiding mechanism, optical source, neural recorder, and optical stimulator are discussed. Next, software modules of closed-loop optogenetic stimulation devices including feature extraction, classification, control, and stimulation parameter modulation are described. Then, the existing devices are categorized into open-loop and closed-loop groups, and the combined operation of their neural recorder, optical stimulator, and control approach is discussed. Finally, the challenges in the design and implementation of closed-loop optogenetic stimulation devices are presented, suggestions on how to tackle these challenges are given, and future directions for closed-loop optogenetics are stated. A generic architecture for closed-loop optogenetic stimulation devices involving both hardware and software perspectives is devised. A comprehensive investigation into the most current miniaturized and tetherless closed-loop optogenetic stimulation devices is given. A detailed comparison of the closed-loop optogenetic stimulation devices is presented.
Antidepressants that increase mitochondrial energetics may elevate risk of treatment-emergent mania
Publisher: Springer Science and Business Media LLC
Date: 13-12-2022
DOI: 10.1038/S41380-022-01888-X
Abstract: Preclinical evidence suggests that antidepressants (ADs) may differentially influence mitochondrial energetics. This study was conducted to investigate the relationship between mitochondrial function and illness vulnerability in bipolar disorder (BD), specifically risk of treatment-emergent mania (TEM). Participants with BD already clinically phenotyped as TEM+ ( n = 176) or TEM− ( n = 516) were further classified whether the TEM associated AD, based on preclinical studies, increased (Mito+, n = 600) or decreased (Mito−, n = 289) mitochondrial electron transport chain (ETC) activity. Comparison of TEM+ rates between Mito+ and Mito− ADs was performed using generalized estimating equations to account for participants exposed to multiple ADs while adjusting for sex, age at time of enrollment into the biobank and BD type (BD-I/schizoaffective vs. BD-II). A total of 692 subjects (62.7% female, 91.4% White, mean age 43.0 ± 14.0 years) including 176 cases (25.3%) of TEM+ and 516 cases (74.7%) of TEM- with previous exposure to Mito+ and/or Mito- antidepressants were identified. Adjusting for age, sex and BD subtype, TEM+ was more frequent with antidepressants that increased (24.7%), versus decreased (13.5%) mitochondrial energetics (OR = 2.21 p = 0.000009). Our preliminary retrospective data suggests there may be merit in reconceptualizing AD classification, not solely based on monoaminergic conventional drug mechanism of action, but additionally based on mitochondrial energetics. Future prospective clinical studies on specific antidepressants and mitochondrial activity are encouraged. Recognizing pharmacogenomic investigation of drug response may extend or overlap to genomics of disease risk, future studies should investigate potential interactions between mitochondrial mechanisms of disease risk and drug response.
Feasibility of investigating differential proteomic expression in depression: implications for biomarker development in mood disorders
Publisher: Springer Science and Business Media LLC
Date: 08-12-2015
DOI: 10.1038/TP.2015.185
Abstract: The objective of this study was to determine whether proteomic profiling in serum s les can be utilized in identifying and differentiating mood disorders. A consecutive s le of patients with a confirmed diagnosis of unipolar (UP n =52) or bipolar depression (BP-I n =46, BP-II n =49) and controls ( n =141) were recruited. A 7.5-ml blood s le was drawn for proteomic multiplex profiling of 320 proteins utilizing the Myriad RBM Discovery Multi-Analyte Profiling platform. After correcting for multiple testing and adjusting for covariates, growth differentiation factor 15 (GDF-15), hemopexin (HPX), hepsin (HPN), matrix metalloproteinase-7 (MMP-7), retinol-binding protein 4 (RBP-4) and transthyretin (TTR) all showed statistically significant differences among groups. In a series of three post hoc analyses correcting for multiple testing, MMP-7 was significantly different in mood disorder (BP-I+BP-II+UP) vs controls, MMP-7, GDF-15, HPN were significantly different in bipolar cases (BP-I+BP-II) vs controls, and GDF-15, HPX, HPN, RBP-4 and TTR proteins were all significantly different in BP-I vs controls. Good diagnostic accuracy (ROC-AUC⩾0.8) was obtained most notably for GDF-15, RBP-4 and TTR when comparing BP-I vs controls. While based on a small s le not adjusted for medication state, this discovery s le with a conservative method of correction suggests feasibility in using proteomic panels to assist in identifying and distinguishing mood disorders, in particular bipolar I disorder. Replication studies for confirmation, consideration of state vs trait serial assays to delineate proteomic expression of bipolar depression vs previous mania, and utility studies to assess proteomic expression profiling as an advanced decision making tool or companion diagnostic are encouraged.
Intravenous Ketamine for Adolescents with Treatment-Resistant Depression: An Open-Label Study
Publisher: Mary Ann Liebert Inc
Date: 09-2018
Efficacy, Safety, and Durability of Repeated Ketamine Infusions for Comorbid Posttraumatic Stress Disorder and Treatment-Resistant Depression
Publisher: Physicians Postgraduate Press, Inc
Date: 27-06-2018
DOI: 10.4088/JCP.17M11634
Electrical resistance increases at the tissue-electrode interface as an early response to nucleus accumbens deep brain stimulation
Publisher: IEEE
Date: 08-2016
Hierarchical estimation of neural activity through explicit identification of temporally synchronous spikes
Publisher: Elsevier BV
Date: 08-2017
Determination of neurotransmitters and their metabolites using one- and two-dimensional liquid chromatography with acidic potassium permanganate chemiluminescence detection
Publisher: Springer Science and Business Media LLC
Date: 07-12-2013
DOI: 10.1007/S00216-013-7514-9
Abstract: High-performance liquid chromatography with chemiluminescence detection based on the reaction with acidic potassium permanganate and formaldehyde was explored for the determination of neurotransmitters and their metabolites. The neurotransmitters norepinephrine and dopamine were quantified in the left and right hemispheres of rat hippoc us, nucleus accumbens and prefrontal cortex, and the metabolites vanillylmandelic acid, 3,4-dihydrophenylacetic acid, 5-hydroxyindole-3-acetic acid and homovanillic acid were identified in human urine. Under optimised chemiluminescence reagent conditions, the limits of detection for these analytes ranged from 2.5 × 10(-8) to 2.5 × 10(-7) M. For the determination of neurotransmitter metabolites in urine, a two-dimensional high-performance liquid chromatography (2D-HPLC) separation operated in heart-cutting mode was developed to overcome the peak capacity limitations of the one-dimensional separation. This approach provided the greater separation power of 2D-HPLC with analysis times comparable to conventional one-dimensional separations.
Development of a Compact Rectenna for Wireless Powering of a Head-Mountable Deep Brain Stimulation Device
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2014
A miniature energy harvesting rectenna for operating a head-mountable deep brain stimulation device
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2015
Adolescent mental health education InSciEd Out: a case study of an alternative middle school population
Publisher: Springer Science and Business Media LLC
Date: 03-04-2018
DOI: 10.1186/S12967-018-1459-X
Abstract: Mental illness contributes substantially to global disease burden, particularly when illness onset occurs during youth and help-seeking is delayed and/or limited. Yet, few mental health promotion interventions target youth, particularly those with or at high risk of developing mental illness (“at-risk” youth). Community-based translational research has the capacity to identify and intervene upon barriers to positive health outcomes. This is especially important for integrated care in at-risk youth populations. Here the Integrated Science Education Outreach (InSciEd Out) program delivered a novel school-based anti-stigma intervention in mental health to a cohort of seventh and eighth grade at-risk students. These students were assessed for changes in mental health knowledge, stigmatization, and help-seeking intentions via a classroom activity, surveys, and teacher interviews. Descriptive statistics and Cohen’s d effect sizes were employed to assess pre–post changes. Inferential statistical analyses were also conducted on pilot results to provide a benchmark to inform future studies. Elimination of mental health misconceptions (substance weakness p = 0.00 recovery p = 0.05 prevention p = 0.05 violent p = 0.05) was accompanied by slight gains in mental health literacy (d = 0.18) and small to medium improvements in help-seeking intentions (anxiety d = 0.24 depression d = 0.48 substance d = 0.43 psychosis d = 0.53). Within this particular cohort of students, stigma was exceptionally low at baseline and remained largely unchanged. Teacher narratives revealed positive teacher views of programming, increased student openness to talk about mental illness, and higher peer and self-acceptance of mental health diagnoses and help-seeking. Curricular-based efforts focused on mental illness in an alternative school setting are feasible and integrated well into general curricula under the InSciEd Out framework. Preliminary data suggest the existence of unique help-seeking barriers in at-risk youth. Increased focus upon community-based programming has potential to bridge gaps in translation, bringing this critical population to clinical care in pursuit of improved mental health for all. Trial registration ClinicalTrials.gov, ID:NCT02680899. Registered 12 February 2016, t2/show/NCT02680899
Development of a miniature device for emerging deep brain stimulation paradigms
Publisher: Public Library of Science (PLoS)
Date: 21-02-2019
Inflammatory Mechanisms in Parkinson’s Disease: From Pathogenesis to Targeted Therapies
Publisher: SAGE Publications
Date: 13-02-2021
Abstract: Inflammation is a critical factor contributing to the progressive neurodegenerative process observed in Parkinson’s disease (PD). Microglia, the immune cells of the central nervous system, are activated early in PD pathogenesis and can both trigger and propagate early disease processes via innate and adaptive immune mechanisms such as upregulated immune cells and antibody-mediated inflammation. Downstream cytokines and gene regulators such as microRNA (miRNA) coordinate later disease course and mediate disease progression. Biomarkers signifying the inflammatory and neurodegenerative processes at play within the central nervous system are of increasing interest to clinical teams. To be effective, such biomarkers must achieve the highest sensitivity and specificity for predicting PD risk, confirming diagnosis, or monitoring disease severity. The aim of this review was to summarize the current preclinical and clinical evidence that suggests that inflammatory processes contribute to the initiation and progression of neurodegenerative processes in PD. In this article, we further summarize the data about main inflammatory biomarkers described in PD to date and their potential for regulation as a novel target for disease-modifying pharmacological strategies.
Disrupting disordered neurocircuitry: Treating refractory psychiatric illness with neuromodulation
Publisher: Elsevier BV
Date: 06-2009
DOI: 10.4065/84.6.522
The role of hypernitrosylation in the pathogenesis and pathophysiology of neuroprogressive diseases
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.NEUBIOREV.2017.07.017
Abstract: There is a wealth of data indicating that de novo protein S-nitrosylation in general and protein transnitrosylation in particular mediates the bulk of nitric oxide signalling. These processes enable redox sensing and facilitate homeostatic regulation of redox dependent protein signalling, function, stability and trafficking. Increased S-nitrosylation in an environment of increasing oxidative and nitrosative stress (O&NS) is initially a protective mechanism aimed at maintaining protein structure and function. When O&NS becomes severe, mechanisms governing denitrosylation and transnitrosylation break down leading to the pathological state referred to as hypernitrosylation (HN). Such a state has been implicated in the pathogenesis and pathophysiology of several neuropsychiatric and neurodegenerative diseases and we investigate its potential role in the development and maintenance of neuroprogressive disorders. In this paper, we propose a model whereby the hypernitrosylation of a range of functional proteins and enzymes lead to changes in activity which conspire to produce at least some of the core abnormalities contributing to the development and maintenance of pathology in these illnesses.
TinyFSCV: FSCV for the Masses
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2020
Continuation phase intravenous ketamine in adults with treatment-resistant depression
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.JAD.2016.09.008
Abstract: Little is known about the antidepressive effects of repeated intravenous ketamine infusions beyond the acute phase of treatment in patients with refractory depression. Twelve subjects with treatment-resistant non-psychotic unipolar or bipolar major depression and suicidal ideation were given repeated (up to 6) thrice-weekly acute-phase intravenous infusions of ketamine (0.5mg/kg, administered over 100min). Those who remitted during acute-phase treatment received continuation-phase treatment that consisted of 4 weekly ketamine infusions, followed by 4 weeks of post-continuation phase follow-up (during which no further ketamine infusions were administered). Clinical measures were assessed at baseline, at 24h following each infusion, at the last acute-phase observation, and during continuation and post-continuation follow-up (acute phase remitters only). Of the 12 enrollees, 5 (41.7%) remitted and 7 (58.3%) responded to ketamine treatment during the acute-phase. All five subjects who remitted during the acute-phase experienced further depressive symptom improvement during continuation-phase treatment. Four subjects lost remission status during the post-continuation phase, but all were still classified as positive treatment responders at the end of the post-continuation phase. Adverse effects were generally mild and transient during acute- and continuation-phase treatment however, one subject developed behavioral outbursts and suicide threats during follow-up while hospitalized, and one subject died by suicide several weeks after the end of follow-up. This was an uncontrolled feasibility study with a small s le size. The continuation-phase administration of ketamine at weekly intervals to patients with treatment-resistant depression who remitted during acute-phase ketamine treatment can extend the duration of depressive symptom remission. The antidepressive effect of ketamine persisted for several weeks after the end of continuation-phase treatment. Our results highlight the need for close monitoring of subjects who are at high baseline risk for suicide but do not respond clinically to ketamine. CLINICALTRIALS. NCT02094898.
Towards in-vivo ATP sensing
Publisher: IEEE
Date: 11-2016
A Balancing Act: D4Receptor Activation and the Neurobiological Basis of Emotional Learning: Figure 1.
Publisher: Society for Neuroscience
Date: 02-09-2009
Hyperthermia for Major Depressive Disorder?
Publisher: American Medical Association (AMA)
Date: 10-2016
A Low Power Micro Deep Brain Stimulation Device for Murine Preclinical Research
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2013
Supervised, vigorous intensity exercise intervention for depressed female smokers: A pilot study
Publisher: Oxford University Press (OUP)
Date: 09-09-2017
DOI: 10.1093/NTR/NTW208
Insulin-stimulated mTOR activation in peripheral blood mononuclear cells associated with early treatment response to lithium augmentation in rodent model of antidepressant-resistance
Publisher: Springer Science and Business Media LLC
Date: 15-03-2019
DOI: 10.1038/S41398-019-0434-5
Abstract: Lithium has been shown to have some therapeutic efficacy as an adjunctive treatment for intractable forms of major depression. Activation of mammalian target of rapamycin (mTOR) and inhibition of glycogen synthase kinase-3β (GSK3β) have been implicated in its putative mechanisms of action. These proteins are integral components of the insulin signaling pathway, which may serve as a critical co-regulator of drug action. Utilizing an animal model of tricyclic antidepressant resistance, we investigated the relationship between insulin signaling and antidepressant response to lithium augmentation. Pre-treatment with adrenocorticotropic hormone (ACTH 100 µg/day i.p.) for 14 days effectively blocked the immobility-reducing effects of an acute dose of imipramine (10 mg/kg i.p.) in the forced swim test (FST). Lithium augmentation (100 mg/kg i.p.) rescued the antidepressant-like effects of imipramine in this model. Total and phosphorylated ( p ) levels of protein kinase B (Akt), mTOR, and GSK3β protein were quantified in the infralimbic cortex (ILPFC) following FST stress via Western blot. Levels of mTOR and p mTOR were further quantified in isolated peripheral blood mononuclear cells (PBMCs) following insulin stimulation (10 mg/mL for 5 min) via ELISA. Elevated levels of phosphorylated insulin signaling proteins were present in the ILPFC of ACTH-pretreated animals that received both imipramine and lithium, together with a concurrent increase in mTOR activation in PBMCs. Large correlations were observed between immobility time and insulin-stimulated mTOR levels in PBMCs. We propose that PBMC insulin challenge may be a useful probe for predicting antidepressant response to lithium administration, and potentially other therapies acting via similar mechanisms of action.
The role of neurotrophic factors in manic-, anxious- and depressive-like behaviors induced by amphetamine sensitization: Implications to the animal model of bipolar disorder
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.JAD.2018.10.370
Abstract: Bipolar disorder (BD) and substance use disorders share common symptoms, such as behavioral sensitization. Amphetamine-induced behavioral sensitization can serve as an animal model of BD. Neurotrophic factors have an important role in BD pathophysiology. This study evaluated the effects of hetamine sensitization on behavior and neurotrophic factor levels in the brains of rats. Wistar rats received daily intraperitoneal (i.p) injections of dextro hetamine (d-AMPH) 2 mg/kg or saline for 14 days. After seven days of withdrawal, the animals were challenged with d-AMPH (0.5 mg/kg, i.p) and locomotor behavior was assessed. In a second protocol, rats were similarly treated with d-AMPH (2 mg/kg, i.p) for 14 days. After withdrawal, without d-AMPH challenge, depressive- and anxiety-like behaviors were evaluated through forced swimming test and elevated plus maze. Levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin 3 (NT-3), neurotrophin 4/5 (NT-4/5) and glial-derived neurotrophic factor (GDNF) were evaluated in the frontal cortex, hippoc us, and striatum. D-AMPH for 14 days augmented locomotor sensitization to a lower dose of d-AMPH (0.5 mg/kg) after the withdrawal. d-AMPH withdrawal induced depressive- and anxious-like behaviors. BDNF, NGF, and GDNF levels were decreased, while NT-3 and NT-4 levels were increased in brains after d-AMPH sensitization. Although d-AMPH induces manic-like behavior, the mechanisms underlying these effects can also be related to phenotypes of drug abuse. Together, vulnerability to mania-like behavior following d-AMPH challenge and extensive neurotrophic alterations, suggest hetamine-induced behavioral sensitization is a good model of BD pathophysiology.
Differential corticosteroid receptor regulation of mesoaccumbens dopamine efflux during the peak and nadir of the circadian rhythm: A molecular equilibrium in the midbrain?
Publisher: Wiley
Date: 11-2009
DOI: 10.1002/SYN.20682
Abstract: Corticosteroid receptor modulation of mesoaccumbens dopamine neurotransmission is believed to be a key neurobiological mechanism mediating the effects of stress in addiction. Importantly, nucleus accumbens (NAc) subregions (core and shell) are reported to respond differentially to fluctuating basal levels of glucocorticoids, with dopaminergic responses in the core of the NAc being somewhat impervious to fluctuating levels of glucocorticoids relative to the shell. To investigate the corticosteroid receptor mechanisms mediating basal dopamine efflux in the core of the NAc, we have used chrono erometry in combination with stearate-modified graphite paste electrodes in urethane anesthetized male Long-Evans rats during the peak and nadir of the circadian cycle. Blockade of ventral tegmental area low-affinity glucocorticoid (GR) or high-affinity mineralocorticoid (MR) receptors with mifepristone (1 microg/microl) or spironolactone (0.2 microg/microl), respectively, indicated that endogenous phase-dependent corticosteroid receptor activation (GRs during peak MRs during nadir) facilitated extracellular NAc dopamine efflux. Conversely, the alternate receptor's actions appeared inhibitory at these time points (MRs during peak GRs during nadir). Pharmacological activation of either the GR or MR with corticosterone (2 microg/microl) or aldosterone (0.2 microg/microl), respectively, potentiated NAc dopamine efflux, irrespective of circadian phase. Together, these data suggest that dominant corticosteroid receptor activation stimulates tonic mesoaccumbens dopamine transmission, enabling MRs and GRs to differentially maintain basal NAc dopamine release over the course of the circadian cycle. This points to an important molecular mechanism through which relatively stable NAc core dopamine extracellular levels could be maintained in the face of fluctuating corticosterone circadian rhythms.
Portable closed-loop optogenetic stimulation device
Publisher: IEEE
Date: 08-2016
Current landscape, unmet needs, and future directions for treatment of bipolar depression
Publisher: Elsevier BV
Date: 12-2014
KETAMINE FOR TREATMENT-RESISTANT UNIPOLAR AND BIPOLAR MAJOR DEPRESSION: CRITICAL REVIEW AND IMPLICATIONS FOR CLINICAL PRACTICE
Publisher: Hindawi Limited
Date: 06-04-2016
DOI: 10.1002/DA.22505
Abstract: There is an urgent need for more rapidly effective pharmacotherapies for major depressive disorder and bipolar disorder (BP) that are efficacious and tolerable for depressed patients who respond poorly to conventional treatments. Multiple controlled trials have now demonstrated a rapid, nonsustained antidepressive response to a single intravenous infusion of ketamine. Early controlled studies of intranasal or serial infusion therapy appear promising. The effective dose for depression is lower than the typical anesthetic doses, and side-effects are generally mild and transient. The data investigating the adjunctive use of concurrent ketamine in the course of electroconvulsive therapy (ECT) for depression do not suggest efficacy or tolerability. The therapeutic potential of ketamine has stimulated considerable excitement among clinicians, patients, and industry, and has led to the increasing use of ketamine as an off-label substitute for ECT and other antidepressive treatments. This clinical review of ketamine will assess the evidence-based use of ketamine and initial clinical implications of further development of a potentially novel treatment for rapid reduction of symptoms in depressed patients.
Pharmacogenomic Overlap Between Antidepressant Treatment Response in Major Depression & Antidepressant Associated Treatment Emergent Mania in Bipolar Disorder
Publisher: Research Square Platform LLC
Date: 23-06-2023
DOI: 10.21203/RS.3.RS-3045012/V1
Abstract: There is increasing interest in in idualizing treatment selection for more than 25 regulatory approved treatments for major depressive disorder (MDD). Despite an inconclusive efficacy evidence base, antidepressants (ADs) are prescribed for the depressive phase of bipolar disorder with oftentimes an inadequate treatment response and or clinical concern for mood destabilization. This study explored the relationship between antidepressant response in MDD and antidepressant-associated treatment emergent mania (TEM) in bipolar disorder (BD). We conducted a genome-wide association study (GWAS) and polygenic score analysis of TEM and tested its association with a subset of BD-I patients treated with SSRIs or SNRIs. Our results did not identify any genome-wide significant variants although, we found that a higher polygenic score (PGS) for antidepressant response in MDD was associated with higher odds of TEM in BD. Future studies with larger transdiagnostic cohorts treated with antidepressants are encouraged to identify a neurobiological mechanism associated with a spectrum of depression improvement (response- emergent mania).
Preclinical Perspectives on Posttraumatic Stress Disorder Criteria in DSM-5
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2015
An investigation into closed-loop treatment of neurological disorders based on sensing mitochondrial dysfunction
Publisher: Springer Science and Business Media LLC
Date: 13-02-2018
Validation of a Portable Low-Power Deep Brain Stimulation Device Through Anxiolytic Effects in a Laboratory Rat Model
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 09-2017
A model of the mitochondrial basis of bipolar disorder
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.NEUBIOREV.2017.01.014
Abstract: Bipolar disorder phenomenologically is a biphasic disorder of energy availability increased in mania and decreased in depression. In consort, there is accumulating evidence indicating increased mitochondrial respiration and ATP production in bipolar mania which contrasts with decreased mitochondrial function in patients in the euthymic or depressive phase of the illness. Consequently, the central thesis of this paper is that bipolar disorder is due to a phasic dysregulation of mitochondrial biogenergetics. The elements responsible for this dysregulation may thus represent critical treatment targets for mood disorders, and are the subject of this paper. There are many potential mediators of mitochondrial function which collectively are implicated in bipolar disorder. Levels of oxidative stress, pro-inflammatory cytokines and intracellular calcium ions are all higher in bipolar mania than in the euthymic and depressive phases of the illness. Increased levels of calcium ions can partly account for increased oxidative phosphorylation via well documented pathways such as the modulation of the F Details of these pathways are discussed as an explanatory model for the existence of increased ATP generation in mania. We also offer a model explaining the biphasic nature of mitochondrial respiration in bipolar disorder and the transition between mania and depression based on increasing levels of TNFα, ROS, NO, AMPK and SIRT-1 together with the antagonistic relationship between p53 and NF-κB.
A head mountable deep brain stimulation device for laboratory animals
Publisher: Springer Berlin Heidelberg
Date: 2011
A miniature neural recording device
Publisher: IEEE
Date: 03-2016
Stimulation-Induced Transient Nonmotor Psychiatric Symptoms following Subthalamic Deep Brain Stimulation in Patients with Parkinson's Disease: Association with Clinical Outcomes and Neuroanatomical Co
Publisher: S. Karger AG
Date: 2016
DOI: 10.1159/000445076
Abstract: b i Background: /i /b The clinical and neurobiological underpinnings of transient nonmotor (TNM) psychiatric symptoms during the optimization of stimulation parameters in the course of subthalamic nucleus deep brain stimulation (STN-DBS) remain under intense investigation. b i Methods: /i /b Forty-nine patients with refractory Parkinson's disease underwent bilateral STN-DBS implants and were enrolled in a 24-week prospective, naturalistic follow-up study. Patients who exhibited TNM psychiatric manifestations during DBS parameter optimization were evaluated for potential associations with clinical outcome measures. b i Results: /i /b Twenty-nine TNM+ episodes were reported by 15 patients. No differences between TNM+ and TNM- groups were found in motor outcome. However, unlike the TNM- group, TNM+ patients did not report improvement in subsyndromal depression or quality of life. TNM+ episodes were more likely to emerge during bilateral monopolar stimulation of the medial STN. b i Conclusions: /i /b The occurrence of TNM psychiatric symptoms during optimization of stimulation parameters was associated with the persistence of subsyndromal depression and with lower quality of life ratings at 6 months. The neurobiological underpinnings of TNM symptoms are investigated yet remain difficult to explain.
Allostatic Load, Cellular Distress and Treatment Responsivity in Mood Disorders
Publisher: Wiley
Date: 07-2016
DOI: 10.1111/BDI.16_12404
Radio frequency energy harvesting from a feeding source in a passive deep brain stimulation device for murine preclinical research
Publisher: Elsevier BV
Date: 10-2015
DOI: 10.1016/J.MEDENGPHY.2015.07.003
Abstract: This paper presents the development of an energy harvesting circuit for use with a head-mountable deep brain stimulation (DBS) device. It consists of a circular planar inverted-F antenna (PIFA) and a Schottky diode-based Cockcroft-Walton 4-voltage rectifier. The PIFA has the volume of π × 10(2) × 1.5 mm(3), resonance frequency of 915 MHz, and bandwidth of 16 MHz (909-925 MHz) at a return loss of -10 dB. The rectifier offers maximum efficiency of 78% for the input power of -5 dBm at a 5 kΩ load resistance. The developed rectenna operates efficiently at 915 MHz for the input power within -15 dBm to +5 dBm. For operating a DBS device, the DC voltage of 2 V is recorded from the rectenna terminal at a distance of 55 cm away from a 26.77 dBm transmitter in free space. An in-vitro test of the DBS device is presented.
Closed loop deep brain stimulation: an evolving technology
Publisher: Springer Science and Business Media LLC
Date: 07-09-2014
DOI: 10.1007/S13246-014-0297-2
Abstract: Deep brain stimulation is an effective and safe medical treatment for a variety of neurological and psychiatric disorders including Parkinson's disease, essential tremor, dystonia, and treatment resistant obsessive compulsive disorder. A closed loop deep brain stimulation (CLDBS) system automatically adjusts stimulation parameters by the brain response in real time. The CLDBS continues to evolve due to the advancement in the brain stimulation technologies. This paper provides a study on the existing systems developed for CLDBS. It highlights the issues associated with CLDBS systems including feedback signal recording and processing, stimulation parameters setting, control algorithm, wireless telemetry, size, and power consumption. The benefits and limitations of the existing CLDBS systems are also presented. Whilst robust clinical proof of the benefits of the technology remains to be achieved, it has the potential to offer several advantages over open loop DBS. The CLDBS can improve efficiency and efficacy of therapy, eliminate lengthy start-up period for programming and adjustment, provide a personalized treatment, and make parameters setting automatic and adaptive.
Comonitoring of adenosine and dopamine using the Wireless Instantaneous Neurotransmitter Concentration System: proof of principle
Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
Date: 03-2010
Abstract: The authors of previous studies have demonstrated that local adenosine efflux may contribute to the therapeutic mechanism of action of thalamic deep brain stimulation (DBS) for essential tremor. Real-time monitoring of the neurochemical output of DBS-targeted regions may thus advance functional neurosurgical procedures by identifying candidate neurotransmitters and neuromodulators involved in the physiological effects of DBS. This would in turn permit the development of a method of chemically guided placement of DBS electrodes in vivo. Designed in compliance with FDA-recognized standards for medical electrical device safety, the authors report on the utility of the Wireless Instantaneous Neurotransmitter Concentration System (WINCS) for real-time comonitoring of electrical stimulation–evoked adenosine and dopamine efflux in vivo, utilizing fast-scan cyclic voltammetry (FSCV) at a polyacrylonitrile-based (T-650) carbon fiber microelectrode (CFM). The WINCS was used for FSCV, which consisted of a triangle wave scanned between −0.4 and +1.5 V at a rate of 400 V/second and applied at 10 Hz. All voltages applied to the CFM were with respect to an Ag/AgCl reference electrode. The CFM was constructed by aspirating a single T-650 carbon fiber (r = 2.5 μm) into a glass capillary and pulling to a microscopic tip using a pipette puller. The exposed carbon fiber (the sensing region) extended beyond the glass insulation by ~ 50 μm. Proof of principle tests included in vitro measurements of adenosine and dopamine, as well as in vivo measurements in urethane-anesthetized rats by monitoring adenosine and dopamine efflux in the dorsomedial caudate putamen evoked by high-frequency electrical stimulation of the ventral tegmental area and substantia nigra. The WINCS provided reliable, high-fidelity measurements of adenosine efflux. Peak oxidative currents appeared at +1.5 V and at +1.0 V for adenosine, separate from the peak oxidative current at +0.6 V for dopamine. The WINCS detected subsecond adenosine and dopamine efflux in the caudate putamen at an implanted CFM during high-frequency stimulation of the ventral tegmental area and substantia nigra. Both in vitro and in vivo testing demonstrated that WINCS can detect adenosine in the presence of other easily oxidizable neurochemicals such as dopamine comparable to the detection abilities of a conventional hardwired electrochemical system for FSCV. Altogether, these results demonstrate that WINCS is well suited for wireless monitoring of high-frequency stimulation-evoked changes in brain extracellular concentrations of adenosine. Clinical applications of selective adenosine measurements may prove important to the future development of DBS technology.
Mapping depression rating scale phenotypes onto research domain criteria (RDoC) to inform biological research in mood disorders
Publisher: Elsevier BV
Date: 10-2018
Nucleus accumbens deep-brain stimulation efficacy in ACTH-pretreated rats: alterations in mitochondrial function relate to antidepressant-like effects
Publisher: Springer Science and Business Media LLC
Date: 21-06-2016
DOI: 10.1038/TP.2016.84
Abstract: Mitochondrial dysfunction has a critical role in the pathophysiology of mood disorders and treatment response. To investigate this, we established an animal model exhibiting a state of antidepressant treatment resistance in male Wistar rats using 21 days of adrenocorticotropic hormone (ACTH) administration (100 μg per day). First, the effect of ACTH treatment on the efficacy of imipramine (10 mg kg −1 ) was investigated alongside its effect on the prefrontal cortex (PFC) mitochondrial function. Second, we examined the mood-regulatory actions of chronic (7 day) high-frequency nucleus accumbens (NAc) deep-brain stimulation (DBS 130 Hz, 100 μA, 90 μS) and concomitant PFC mitochondrial function. Antidepressant-like responses were assessed in the open field test (OFT) and forced swim test (FST) for both conditions. ACTH pretreatment prevented imipramine-mediated improvement in mobility during the FST ( P .05). NAc DBS effectively improved FST mobility in ACTH-treated animals ( P .05). No improvement in mobility was observed for sham control animals ( P .05). Analyses of PFC mitochondrial function revealed that ACTH-treated animals had decreased capacity for adenosine triphosphate production compared with controls. In contrast, ACTH animals following NAc DBS demonstrated greater mitochondrial function relative to controls. Interestingly, a proportion (30%) of the ACTH-treated animals exhibited heightened locomotor activity in the OFT and exaggerated escape behaviors during the FST, together with general hyperactivity in their home-cage settings. More importantly, the induction of this mania-like phenotype was accompanied by overcompensative increased mitochondrial respiration. Manifestation of a DBS-induced mania-like phenotype in imipramine-resistant animals highlights the potential use of this model in elucidating mechanisms of mood dysregulation.
Fabrication of Biocompatible Enclosures for an Electronic Implant Using 3D Printing
Publisher: Inderscience Publishers
Date: 2016
Stress, Inflammation, and Cellular Vulnerability during Early Stages of Affective Disorders: Biomarker Strategies and Opportunities for Prevention and Intervention
Publisher: Frontiers Media SA
Date: 09-04-2014
Voltage-dependent mania after subthalamic nucleus deep brain stimulation in Parkinson's disease: A case report
Publisher: Elsevier BV
Date: 07-2011
Underlying neurobiology and clinical correlates of mania status after subthalamic nucleus deep brain stimulation in Parkinson's disease: A review of the literature
Publisher: American Psychiatric Association Publishing
Date: 2012
Dynamic insulin-stimulated mTOR/GSK3 signaling in peripheral immune cells: Preliminary evidence for an association with lithium response in bipolar disorder.
Publisher: Wiley
Date: 13-05-2022
DOI: 10.1111/BDI.13081
Abstract: A key mechanism of lithium is the inhibition of glycogen synthase kinase-3β (GSK3β) and activation of mammalian target of rapamycin (mTOR), two contributors to insulin signaling. We explored the relationship between these markers and clinical response to lithium in bipolar disorder (BD). Thirty-four subjects with BD who had been taking lithium for ≥2 years and had a maintenance lithium Alda score defined as either high (≥7 n = 20) or low (≤2 n = 14) were included in the study. Baseline protein expression of GSK3β and mTOR (total and phosphorylated (p)) was obtained from a buffy coat. Peripheral blood mononuclear cells (PBMCs) from a subset of each group (n = 11) were stimulated with insulin (10 µg) and change in protein expression was determined using Western blot. In buffy coat s les, significantly higher levels of pmTOR were present in subjects with an Alda score ≤2 (lithium non-responsive), relative to those with scores ≥7 (lithium-responsive). No differences were observed for pGSK3β. In contrast, functional PBMC responses to 5 min of insulin stimulation demonstrated robust increases in pGSK3β (87.05 ± 43.41%) and pmTOR (105.7 ± 66.48%) in the lithium responsive group only. This contrasted observed decreases in pGSK3β (34.08 ± 16.12%) and pmTOR (37.84 ± 14.39%) 5 mins post-insulin in non-responders. Dynamic increases in pmTOR and pGSK3β post-insulin stimulation may reflect an immunometabolic state that facilitates lithium response. Further prospective analyses are needed to replicate and extend these preliminary findings and further investigate the role of insulin signaling in lithium response in BD.
Wireless instantaneous neurotransmitter concentration sensing system (WINCS) for intraoperative neurochemical monitoring
Publisher: IEEE
Date: 09-2009
Design of a miniature UHF PIFA for DBS implants
Publisher: IEEE
Date: 07-2012
Deep Brain Stimulation
Publisher: Jenny Stanford Publishing
Date: 08-12-2016
Antidepressant actions of lateral habenula deep brain stimulation differentially correlate with CaMKII/GSK3/AMPK signaling locally and in the infralimbic cortex
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.BBR.2016.02.039
Abstract: High frequency deep brain stimulation (DBS) of the lateral habenula (LHb) reduces symptoms of depression in severely treatment-resistant in iduals. Despite the observed therapeutic effects, the molecular underpinnings of DBS are poorly understood. This study investigated the efficacy of high frequency LHb DBS (130Hz 200μA 90μs) in an animal model of tricyclic antidepressant resistance. Further, we reported DBS mediated changes in Ca(2+)/calmodulin-dependent protein kinase (CaMKIIα/β), glycogen synthase kinase 3 (GSK3α/β) and AMP-activated protein kinase (AMPK) both locally and in the infralimbic cortex (IL). Protein expressions were then correlated to immobility time during the forced swim test (FST). Antidepressant actions were quantified via FST. Treatment groups comprised of animals treated with adrenocorticotropic hormone alone (ACTH 100μg/day, 14days, n=7), ACTH with active DBS (n=7), sham DBS (n=8), surgery only (n=8) or control (n=8). Active DBS significantly reduced immobility in ACTH-treated animals (p<0.05). For this group, western blot results demonstrated phosphorylation status of LHb CaMKIIα/β and GSK3α/β significantly correlated to immobility time in the FST. Concurrently, we observed phosphorylation status of CaMKIIα/β, GSK3α/β, and AMPK in the IL to be negatively correlated with antidepressant actions of DBS. These findings suggest that activity dependent phosphorylation of CaMKIIα/β, and GSK3α/β in the LHb together with the downregulation of CaMKIIα/β, GSK3α/β, and AMPK in the IL, contribute to the antidepressant actions of DBS.
Evolution of optogenetic microdevices
Publisher: SPIE-Intl Soc Optical Eng
Date: 25-06-2015
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Discovery Projects - Grant ID: DP230102566
Start Date: 03-2023
End Date: 03-2026
Amount: $649,942.00
Funder: Australian Research Council
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