Effectiveness of Low-Resolution Brain Electromagnetic Tomography Z Score Neurofeedback Comparison with Cognitive Rehabilitation in Depression and Anxiety in Opioid Use Disorder.

Background: Previous studies have shown that conventional neurofeedback (NFB) and cognitive rehabilitation can improve psychological outcomes in people with opioid use disorders (OUDs). However, the effectiveness of Low-Resolution Brain Electromagnetic Tomography (LORETA) Z-score neurofeedback (LZNFB) and attention bias modification training (ABMT) on depression and anxiety of these people has not been investigated yet. The present study aims to compare the effect of these two methods on depression and anxiety of men with OUD under methadone maintenance therapy (MMT). Methods: In this randomized controlled clinical trial with a pre-test, post-test, and follow-up design, 30 men with OUD under MMT were randomly assigned into three groups of LZNFB, ABMT, and control (MMT alone). The LZNFB group underwent LZNFB at 20 sessions. The ABMT using the dot-probe task was provided individually to the second group for 2 weeks at 15 sessions. The Beck Anxiety Inventory and the Beck Depression Inventory were completed by the participants before, immediately after, and 1-month after interventions. The collected data were analyzed in SPSS v.22 software. Results: Both intervention groups showed a significant reduction in anxiety and depression at the post-test phase (p < 0.05), where LZNFB group showed more decrease in anxiety and depression than the ABMT group. This decrease continued in the follow-up period. Conclusion: Both LZNFB and ABMT with the dot-robe task are effective in reducing depression and anxiety of men with OUD under MMT. However, LZNFB is more effective. These findings add to the growing body of literature supporting the effectiveness of NFB and cognitive rehabilitation therapy in treating addiction-related comorbidities.

Global Medical Device Clinical Trials Involving Both the United States and Japan: Key Considerations for Development, Regulatory Approval, and Conduct.

As medical device development becomes increasingly global, the opportunities and potential advantages offered by international clinical trial and regulatory approval strategies are also growing. In particular, medical device clinical trials involving sites in both the United States and Japan and intended to support marketing in both countries may warrant particular consideration, given the similarities in their regulatory systems, patients and clinical practice patterns, and market sizes. Since 2003, the US-Japan Harmonization By Doing (HBD) initiative has been focused on identifying and addressing clinical and regulatory barriers to medical devices access in both countries via collaboration between governmental, academic, and industry stakeholders. Through the efforts of HBD participants, US-Japanese clinical trials have been conducted and the resulting data have supported regulatory approval for marketing in both countries. Based on these experiences, this paper outlines some of the key factors to consider when developing a global clinical trial involving US and Japanese participation. These considerations include the mechanisms for consultation with regulatory authorities on clinical trial strategies, the regulatory framework for clinical trial notification and approval, recruitment and conduct of clinical sites, and lessons learned from specific US-Japanese clinical trial experiences. The goal of this paper is to promote global access to promising medical technologies by assisting potential clinical trial sponsors in understanding when an international strategy may be appropriate and successful.

Utilisation of semiconductor sequencing for detection of actionable fusions in solid tumours.

Oncogenic fusions represent compelling druggable targets in solid tumours highlighted by the recent site agnostic FDA approval of larotrectinib for NTRK rearrangements. However screening for fusions in routinely processed tissue samples is constrained due to degradation of nucleic acid as a result of formalin fixation., To investigate the clinical utility of semiconductor sequencing optimised for detection of actionable fusion transcripts in formalin fixed samples, we have undertaken an analysis of test trending data generated by a clinically validated next generation sequencing platform designed to capture 867 of the most clinically relevant druggable driver-partner oncogenic fusions. Here we show across a real-life cohort of 1112 patients with solid tumours that actionable fusions occur at high frequency (7.4%) with linkage to a wide range of targeted therapy protocols including seven fusion-drug matches with FDA/EMA approval and/or NCCN/ESMO recommendations and 80 clinical trials. The more prevalent actionable fusions identified were independent of tumour type in keeping with signalling via evolutionary conserved RAS/RAF/MEK/ERK, PI3K/AKT/MTOR, PLCy/PKC and JAK/STAT pathways. Taken together our data indicates that semiconductor sequencing for detection of actionable fusions can be integrated into routine diagnostic pathology workflows enabling the identification of personalised treatment options that have potential to improve clinical cancer management across many tumour types.

Utilisation of semiconductor sequencing for the detection of predictive biomarkers in glioblastoma.

The standard treatment for glioblastoma involves a combination of surgery, radiation and chemotherapy but have limited impact on survival. The exponential increase in targeted agents directed at pivotal oncogenic pathways now provide new therapeutic opportunities for this tumour type. However, lack of comprehensive precision oncology testing at diagnosis means such therapeutic opportunities are potentially overlooked. To investigate the role of semiconductor sequencing for detection of predictive biomarkers in routine glioblastoma samples we have undertaken analysis of test trending data generated by a clinically validated next generation sequencing platform designed to capture actionable genomic variants distributed across 505 genes. Analysis was performed across a cohort of 55 glioblastoma patients. Analysis of trending data has revealed a complex and rich actionable mutational landscape in which 166 actionable mutations were detected across 36 genes linked to 17 off label targeted therapy protocols and 111 clinical trials. The majority of patients harboured three or more actionable mutations affecting key cancer related regulatory networks including the PI3K/AKT/MTOR and RAS/RAF/MEK/MAPK signalling pathways, DNA-damage repair pathways and cell cycle checkpoints. Linkage with immunotherapy and PARP inhibitors was identified in 44% of glioblastoma patients as a consequence of alterations in DNA-damage repair genes. Taken together our data indicates that precision oncology testing utilising semiconductor sequencing can be used to identify a broad therapeutic armamentarium of targeted therapies and immunotherapies that can be potentially employed for the improved clinical management of glioblastoma patients.

A Proposed Brain-, Spine-, and Mental- Health Screening Methodology (NEUROSCREEN) for Healthcare Systems: Position of the Society for Brain Mapping and Therapeutics.

The COVID-19 pandemic has accelerated neurological, mental health disorders, and neurocognitive issues. However, there is a lack of inexpensive and efficient brain evaluation and screening systems. As a result, a considerable fraction of patients with neurocognitive or psychobehavioral predicaments either do not get timely diagnosed or fail to receive personalized treatment plans. This is especially true in the elderly populations, wherein only 16% of seniors say they receive regular cognitive evaluations. Therefore, there is a great need for development of an optimized clinical brain screening workflow methodology like what is already in existence for prostate and breast exams. Such a methodology should be designed to facilitate objective early detection and cost-effective treatment of such disorders. In this paper we have reviewed the existing clinical protocols, recent technological advances and suggested reliable clinical workflows for brain screening. Such protocols range from questionnaires and smartphone apps to multi-modality brain mapping and advanced imaging where applicable. To that end, the Society for Brain Mapping and Therapeutics (SBMT) proposes the Brain, Spine and Mental Health Screening (NEUROSCREEN) as a multi-faceted approach. Beside other assessment tools, NEUROSCREEN employs smartphone guided cognitive assessments and quantitative electroencephalography (qEEG) as well as potential genetic testing for cognitive decline risk as inexpensive and effective screening tools to facilitate objective diagnosis, monitor disease progression, and guide personalized treatment interventions. Operationalizing NEUROSCREEN is expected to result in reduced healthcare costs and improving quality of life at national and later, global scales.

Comparing LORETA Z Score Neurofeedback and Cognitive Rehabilitation Regarding Their Effectiveness in Reducing Craving in Opioid Addicts.

Introduction: Previous studies have shown that conventional neurofeedback and cognitive modification treatments have numerous psychological benefits for patients with substance use disorders. However, the effectiveness of LORETA (Low-Resolution Brain Electromagnetic Tomography) Z Score Neurofeedback (LZNFB) and cognitive rehabilitation therapy in reducing opioid craving has not been investigated. Thus, the present study aimed to compare the effectiveness of LZNFB and cognitive rehabilitation therapy with Methadone Maintenance Treatment (MMT) in reducing craving in patients with opioid use disorder. Methods: Thirty patients with opioid use disorder undergoing MMT were randomly assigned into three groups: LZNFB with MMT, cognitive rehabilitation with MMT (as experimental groups), and MMT alone control group. The LZNFB and cognitive rehabilitation groups received 20 and 15 sessions of treatment, respectively. The three groups were assessed using several questionnaires and dot-probe task at pretest, posttest, and one-month follow-up. Results: The results showed that both experimental groups accomplished a significantly greater reduction in opioid craving than MMT alone group at posttest and follow-up (P<0.05). The LZNFB plus MMT group showed a greater decrease in opioid craving than the cognitive rehabilitation plus MMT group. In addition, the cognitive rehabilitation plus MMT group experienced greater improvement in attentional bias towards craving cues than the LZNFB with MMT group at posttest and follow-up. Finally, the LZNFB plus MMT group and cognitive rehabilitation plus MMT group got higher scores on the recovery assessment scale than MMT alone group at posttest and follow-up. According to study results, LZNFB training is more effective than cognitive rehabilitation in decreasing cravings and improving the quality of life in addiction to opioids. Conclusion: The current study's findings provided preliminary support for the effectiveness of LZNFB and cognitive rehabilitation in reducing opioid craving, improving attentional bias towards craving cues, and the quality of life among Iranian opioid use patients. Highlights: LZNFB training showed higher decrease in opioid craving than the Cognitive rehabilitation in opioid addicts.Cognitive rehabilitation group experienced greater improvement on attentional bias towards craving cues than LZNFB.LZNFB and Cognitive rehabilitation with MMT group got higher scores on the recovery assessment scale than MMT alone group.LZNFB training is more effective than Cognitive Rehabilitation in decreasing of craving in addiction. opioids. Plain Language Summary: Addiction is a chronic relapsing disease that makes many problems for human society. Routine medical treatments are not completely effective and they have relapse. New forms of non-medical treatments such as neurofeedback and cognitive rehabilitation are effective and safe without impressive side effects . This article shows the efficacy of above mentioned interventions for decrease craving and control of this problem.

Japan-USA Orbital Atherectomy for Calcific Coronary Lesions: COAST Study, Harmonization by Doing Proof-of-Concept.

Effective treatment strategies and medical devices continue to be needed in Japan and the United States of America (US) to mitigate the growing burden of cardiovascular disease and coronary heart disease. Unfortunately, there can be a delay in gaining cardiovascular device approval in Japan after a device has already been approved and is in use in the US. The Harmonization by Doing (HBD) program; however, can eliminate this delay and reduce the cost of completing a clinical trial in Japan. The HBD proof-of-concept study, COAST, resulted in approval of the Diamondback 360® Coronary Orbital Atherectomy System Micro Crown simultaneously in Japan and the US on the same day. Subsequently, the Diamondback 360® Coronary OAS Classic Crown also received approval in Japan. The COAST study provides further evidence that global clinical trials via HBD for medical devices are practical and advantageous.

Synthesis and pharmacological characterisation of arctigenin analogues as antagonists of AMPA and kainate receptors.

(-)-Arctigenin and a series of new analogues have been synthesised and then tested for their potential as AMPA and kainate receptor antagonists of human homomeric GluA1 and GluK2 receptors expressed in HEK293 cells using a Ca2+ influx assay. In general, these compounds showed antagonist activity at both receptors with greater activity evident at AMPARs. Schild analysis indicates that a spirocyclic analogue 6c acts as a non-competitive antagonist. Molecular docking studies in which 6c was docked into the X-ray crystal structure of the GluA2 tetramer suggest that (-)-arctigenin and its analogues bind in the transmembrane domain in a similar manner to the known AMPA receptor non-competitive antagonists GYKI53655 and the antiepileptic drug perampanel. The arctigenin derivatives described herein may serve as novel leads for the development of drugs for the treatment of epilepsy.

Neuroscience20 (BRAIN20, SPINE20, and MENTAL20) Health Initiative: A Global Consortium Addressing the Human and Economic Burden of Brain, Spine, and Mental Disorders Through Neurotech Innovations and Policies.

Neurological disorders significantly impact the world's economy due to their often chronic and life-threatening nature afflicting individuals which, in turn, creates a global disease burden. The Group of Twenty (G20) member nations, which represent the largest economies globally, should come together to formulate a plan on how to overcome this burden. The Neuroscience-20 (N20) initiative of the Society for Brain Mapping and Therapeutics (SBMT) is at the vanguard of this global collaboration to comprehensively raise awareness about brain, spine, and mental disorders worldwide. This paper aims to provide a comprehensive review of the various brain initiatives worldwide and highlight the need for cooperation and recommend ways to bring down costs associated with the discovery and treatment of neurological disorders. Our systematic search revealed that the cost of neurological and psychiatric disorders to the world economy by 2030 is roughly $16T. The cost to the economy of the United States is $1.5T annually and growing given the impact of COVID-19. We also discovered there is a shortfall of effective collaboration between nations and a lack of resources in developing countries. Current statistical analyses on the cost of neurological disorders to the world economy strongly suggest that there is a great need for investment in neurotechnology and innovation or fast-tracking therapeutics and diagnostics to curb these costs. During the current COVID-19 pandemic, SBMT, through this paper, intends to showcase the importance of worldwide collaborations to reduce the population's economic and health burden, specifically regarding neurological/brain, spine, and mental disorders.

Registry Assessment of Peripheral Interventional Devices objective performance goals for superficial femoral and popliteal artery peripheral vascular interventions.

BACKGROUND: The Superficial Femoral Artery-Popliteal EvidencE Development Study Group developed contemporary objective performance goals (OPGs) for peripheral vascular interventions (PVI) for superficial femoral artery (SFA)-popliteal artery disease using the Registry Assessment of Peripheral Interventional Devices. METHODS: The Society for Vascular Surgery Vascular Quality Initiative PVI registry from January 2010 to October 2016 was used to develop OPGs based on SFA-popliteal procedures (n = 21,377) for intermittent claudication and critical limb ischemia (CLI). OPGs included 1-year rates for target lesion revascularization (TLR), major amputation, and 1 and 4-year survival rates. OPGs were calculated for the SFA and popliteal arteries and stratified by four treatments: angioplasty alone (percutaneous transluminal angioplasty [PTA]), self-expanding stenting, atherectomy, and any treatment type. Outcomes were illustrated by unadjusted Kaplan-Meier analyses. RESULTS: Cohorts included PTA (n = 7505), stenting (n = 9217), atherectomy (n = 2510) and any treatment (n = 21,377). The mean age was 69 years, 58% were male, 79% were White, and 52% had CLI. The freedom from TLR OPGs at 1 year in the SFA were 80.3% (PTA), 83.2% (stenting), 83.9% (atherectomy), and 81.9% (any treatments). The freedom from TLR OPGs at 1 year in the popliteal were 81.3% (PTA), 81.3% (stenting), 80.2% (atherectomy), and 81.1% (any treatments). The freedom from major amputation OPGs at 1 year after SFA PVI were 93.4% (PTA), 95.7% (stenting), 95.1% (atherectomy), and 94.8% (any treatments). The freedom from major amputation OPG at 1 year after popliteal PVI were 90.5% (PTA), 93.7% (stenting), 91.8% (atherectomy), and 91.8%, (any treatments). The 4-year survival OPGs after SFA PVI were 76% (PTA), 80% (stenting), 82% (atherectomy), and 79% (any treatments), and for the popliteal artery were 72% (PTA), 77% (stenting), 82% (atherectomy), and 75% (any treatment). On a multivariable analysis, which included patient-level, leg-level, and lesion-level covariates, CLI was the single independent factor associated with increased TLR, amputation, and mortality. CONCLUSIONS: The Superficial Femoral Artery-Popliteal EvidencE Development OPGs define a new, contemporary benchmark for SFA-popliteal interventions using a large subset of real-world evidence to inform more efficient peripheral device clinical trial designs to support regulatory and clinical decision-making. It is appropriate to discuss proposals intended for regulatory approval with the US Food and Drug Administration to refine the OPG to match the specific trial population. The OPGs may be updated using coordinated registry networks to assess long-term real-world device performance.

Structural basis of subtype-selective competitive antagonism for GluN2C/2D-containing NMDA receptors.

N-Methyl-D-aspartate receptors (NMDARs) play critical roles in the central nervous system. Their heterotetrameric composition generates subtypes with distinct functional properties and spatio-temporal distribution in the brain, raising the possibility for subtype-specific targeting by pharmacological means for treatment of neurological diseases. While specific compounds for GluN2A and GluN2B-containing NMDARs are well established, those that target GluN2C and GluN2D are currently underdeveloped with low potency and uncharacterized binding modes. Here, using electrophysiology and X-ray crystallography, we show that UBP791 ((2S*,3R*)-1-(7-(2-carboxyethyl)phenanthrene-2-carbonyl)piperazine-2,3-dicarboxylic acid) inhibits GluN2C/2D with 40-fold selectivity over GluN2A-containing receptors, and that a methionine and a lysine residue in the ligand binding pocket (GluN2D-Met763/Lys766, GluN2C-Met736/Lys739) are the critical molecular elements for the subtype-specific binding. These findings led to development of UBP1700 ((2S*,3R*)-1-(7-(2-carboxyvinyl)phenanthrene-2-carbonyl)piperazine-2,3-dicarboxylic acid) which shows over 50-fold GluN2C/2D-selectivity over GluN2A with potencies in the low nanomolar range. Our study shows that the L-glutamate binding site can be targeted for GluN2C/2D-specific inhibition.

Filling a Niche in "Ligand Space" with Bulky, Electron-Poor Phosphorus(III) Alkoxides.

The chemistry of phosphorus(III) ligands, which are of key importance in coordination chemistry, organometallic chemistry and catalysis, is dominated by relatively electron-rich species. Many of the electron-poor PIII ligands that are readily available have relatively small steric profiles. As such, there is a significant gap in "ligand space" where more sterically bulky, electron-poor PIII ligands are needed. This contribution discusses the coordination chemistry, steric and electronic properties of PIII ligands bearing highly fluorinated alkoxide groups of the general form PRn (ORF )3-n , where R=Ph, RF =C(H)(CF3 )2 and C(CF3 )3 ; n=1-3. These ligands are simple to synthesize and a range of experimental and theoretical methods suggest that their steric and electronic properties can be "tuned" by modification of their substituents, making them excellent candidates for large, electron-poor ligands.

Registry Assessment of Peripheral Interventional Devices (RAPID): Registry assessment of peripheral interventional devices core data elements.

OBJECTIVE: The current state of evaluating patients with peripheral artery disease and more specifically of evaluating medical devices used for peripheral vascular intervention (PVI) remains challenging because of the heterogeneity of the disease process, the multiple physician specialties that perform PVI, the multitude of devices available to treat peripheral artery disease, and the lack of consensus about the best treatment approaches. Because PVI core data elements are not standardized across clinical care, clinical trials, and registries, aggregation of data across different data sources and physician specialties is currently not feasible. METHODS: Under the auspices of the U.S. Food and Drug Administration's Medical Device Epidemiology Network initiative-and its PASSION (Predictable and Sustainable Implementation of the National Registries) program, in conjunction with other efforts to align clinical data standards-the Registry Assessment of Peripheral Interventional Devices (RAPID) workgroup was convened. RAPID is a collaborative, multidisciplinary effort to develop a consensus lexicon and to promote interoperability across clinical care, clinical trials, and national and international registries of PVI. RESULTS: The current manuscript presents the initial work from RAPID to standardize clinical data elements and definitions, to establish a framework within electronic health records and health information technology procedural reporting systems, and to implement an informatics-based approach to promote the conduct of pragmatic clinical trials and registry efforts in PVI. CONCLUSIONS: Ultimately, we hope this work will facilitate and improve device evaluation and surveillance for patients, clinicians, health outcomes researchers, industry, policymakers, and regulators.

Registry Assessment of Peripheral Interventional Devices (RAPID)　- Registry Assessment of Peripheral Interventional Devices Core Data Elements.

BACKGROUND: The current state of evaluating patients with peripheral artery disease and more specifically of evaluating medical devices used for peripheral vascular intervention (PVI) remains challenging because of the heterogeneity of the disease process, the multiple physician specialties that perform PVI, the multitude of devices available to treat peripheral artery disease, and the lack of consensus about the best treatment approaches. Because PVI core data elements are not standardized across clinical care, clinical trials, and registries, aggregation of data across different data sources and physician specialties is currently not feasible.Methods and Results:Under the auspices of the U.S. Food and Drug Administration's Medical Device Epidemiology Network initiative-and its PASSION (Predictable and Sustainable Implementation of the National Registries) program, in conjunction with other efforts to align clinical data standards-the Registry Assessment of Peripheral Interventional Devices (RAPID) workgroup was convened. RAPID is a collaborative, multidisciplinary effort to develop a consensus lexicon and to promote interoperability across clinical care, clinical trials, and national and international registries of PVI. The current manuscript presents the initial work from RAPID to standardize clinical data elements and definitions, to establish a framework within electronic health records and health information technology procedural reporting systems, and to implement an informatics-based approach to promote the conduct of pragmatic clinical trials and registry efforts in PVI. CONCLUSIONS: Ultimately, we hope this work will facilitate and improve device evaluation and surveillance for patients, clinicians, health outcomes researchers, industry, policymakers, and regulators.

Structure of Amido Pyridinium Betaines: Persistent Intermolecular C-H⋠⋠⋠N Hydrogen Bonding in Solution.

A hydrogen bond of the type C-H⋅⋅⋅X (X=O or N) is known to influence the structure and function of chemical and biological systems in solution. C-H⋅⋅⋅O hydrogen bonding in solution has been extensively studied, both experimentally and computationally, whereas the equivalent thermodynamic parameters have not been enumerated experimentally for C-H⋅⋅⋅N hydrogen bonds. This is, in part, due to the lack of systems that exhibit persistent C-H⋅⋅⋅N hydrogen bonds in solution. Herein, a class of molecule based on a biologically active norharman motif that exhibits unsupported intermolecular C-H⋅⋅⋅N hydrogen bonds in solution has been described. A pairwise interaction leads to dimerisation to give bond strengths of about 7 kJ mol-1 per hydrogen bond, which is similar to chemically and biologically relevant C-H⋅⋅⋅O hydrogen bonding. The experimental data is supported by computational work, which provides additional insight into the hydrogen bonding by consideration of electrostatic and orbital interactions and allowed a comparison between calculated and extrapolated NMR chemical shifts.

LORETA EEG phase reset of the default mode network.

OBJECTIVES: The purpose of this study was to explore phase reset of 3-dimensional current sources in Brodmann areas located in the human default mode network (DMN) using Low Resolution Electromagnetic Tomography (LORETA) of the human electroencephalogram (EEG). METHODS: The EEG was recorded from 19 scalp locations from 70 healthy normal subjects ranging in age from 13 to 20 years. A time point by time point computation of LORETA current sources were computed for 14 Brodmann areas comprising the DMN in the delta frequency band. The Hilbert transform of the LORETA time series was used to compute the instantaneous phase differences between all pairs of Brodmann areas. Phase shift and lock durations were calculated based on the 1st and 2nd derivatives of the time series of phase differences. RESULTS: Phase shift duration exhibited three discrete modes at approximately: (1) 25 ms, (2) 50 ms, and (3) 65 ms. Phase lock duration present primarily at: (1) 300-350 ms and (2) 350-450 ms. Phase shift and lock durations were inversely related and exhibited an exponential change with distance between Brodmann areas. CONCLUSIONS: The results are explained by local neural packing density of network hubs and an exponential decrease in connections with distance from a hub. The results are consistent with a discrete temporal model of brain function where anatomical hubs behave like a "shutter" that opens and closes at specific durations as nodes of a network giving rise to temporarily phase locked clusters of neurons for specific durations.

Quantitative EEG and neurofeedback in children and adolescents: anxiety disorders, depressive disorders, comorbid addiction and attention-deficit/hyperactivity disorder, and brain injury.

This article explores the science surrounding neurofeedback. Both surface neurofeedback (using 2-4 electrodes) and newer interventions, such as real-time z-score neurofeedback (electroencephalogram [EEG] biofeedback) and low-resolution electromagnetic tomography neurofeedback, are reviewed. The limited literature on neurofeedback research in children and adolescents is discussed regarding treatment of anxiety, mood, addiction (with comorbid attention-deficit/hyperactivity disorder), and traumatic brain injury. Future potential applications, the use of quantitative EEG for determining which patients will be responsive to medications, the role of randomized controlled studies in neurofeedback research, and sensible clinical guidelines are considered.

Halogen-bonded liquid crystals of 4-alkoxystilbazoles with molecular iodine: a very short halogen bond and unusual mesophase stability.

Complexes of molecular iodine with alkoxystilbazoles are liquid crystals with unusually high mesophase stability, predicated on an intermolecular I···I contact. Attempts to prepare analogous complexes with bromine led to an unexpected electrophilic substitution product.

The psychological and neurological bases of leader self-complexity and effects on adaptive decision-making.

Complex contexts and environments require leaders to be highly adaptive and to adjust their behavioral responses to meet diverse role demands. Such adaptability may be contingent upon leaders having requisite complexity to facilitate effectiveness across a range of roles. However, there exists little empirical understanding of the etiology or basis of leader complexity. To this end, we conceptualized a model of leader self-complexity that is inclusive of both the mind (the complexity of leaders' self-concepts) and the brain (the neuroscientific basis for complex leadership). We derived psychometric and neurologically based measures, the latter based on quantitative electroencephalogram (qEEG) profiles of leader self-complexity, and tested their separate effects on the adaptive decision-making of 103 military leaders. Results demonstrated that both measures accounted for unique variance in external ratings of adaptive decision-making. We discuss how these findings provide a deeper understanding of the latent and dynamic mechanisms that underpin leaders' self-complexity and their adaptability.