Multivariate meta-analyses of mitochondrial complex I and IV in major depressive disorder, bipolar disorder, schizophrenia, Alzheimer disease, and Parkinson disease

Complex I (NADH dehydrogenase, NDU) and complex IV (cytochrome-c-oxidase, COX) of the mitochondrial electron transport chain have been implicated in the pathophysiology of major psychiatric disorders, such as major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ), as well as in neurodegenerative disorders, such as Alzheimer disease (AD) and Parkinson disease (PD). We conducted meta-analyses comparing complex I and IV in each disorder MDD, BD, SZ, AD, and PD, as well as in normal aging. The electronic databases Pubmed, EMBASE, CENTRAL, and Google Scholar, were searched for studies published between 1980 and 2018. Of 2049 screened studies, 125 articles were eligible for the meta-analyses. Complex I and IV were assessed in peripheral blood, muscle biopsy, or postmortem brain at the level of enzyme activity or subunits. Separate meta-analyses of mood disorder studies, MDD and BD, revealed moderate effect sizes for similar abnormality patterns in the expression of complex I with SZ in frontal cortex, cerebellum and striatum, whereas evidence for complex IV alterations was low. By contrast, the neurodegenerative disorders, AD and PD, showed strong effect sizes for shared deficits in complex I and IV, such as in peripheral blood, frontal cortex, cerebellum, and substantia nigra. Beyond the diseased state, there was an age-related robust decline in both complexes I and IV. In summary, the strongest support for a role for complex I and/or IV deficits, is in the pathophysiology of PD and AD, and evidence is less robust for MDD, BD, or SZ

Distribution of Response Time, Cortical, and Cardiac Correlates during Emotional Interference in Persons with Subclinical Psychotic Symptoms

A psychosis phenotype can be observed below the threshold of clinical detection. The study aimed to investigate whether subclinical psychotic symptoms are associated with deficits in controlling emotional interference, and whether cortical brain and cardiac correlates of these deficits can be detected using functional near-infrared spectroscopy (fNIRS). A data set derived from a community sample was obtained from the Zurich Program for Sustainable Development of Mental Health Services. 174 subjects (mean age 29.67 ± 6.41, 91 females) were assigned to four groups ranging from low to high levels of subclinical psychotic symptoms (derived from the Symptom Checklist-90-R). Emotional interference was assessed using the emotional Stroop task comprising neutral, positive, and negative conditions. Statistical distributional methods based on delta plots [behavioral response time (RT) data] and quantile analysis (fNIRS data) were applied to evaluate the emotional interference effects. Results showed that both interference effects and disorder-specific (i.e., group-specific) effects could be detected, based on behavioral RTs, cortical hemodynamic signals (brain correlates), and heart rate variability (cardiac correlates). Subjects with high compared to low subclinical psychotic symptoms revealed significantly reduced amplitudes in dorsolateral prefrontal cortices (interference effect, p < 0.001) and middle temporal gyrus (disorder-specific group effect, p < 0.001), supported by behavioral and heart rate results. The present findings indicate that distributional analyses methods can support the detection of emotional interference effects in the emotional Stroop. The results suggested that subjects with high subclinical psychosis exhibit enhanced emotional interference effects. Based on these observations, subclinical psychosis may therefore prove to represent a valid extension of the clinical psychosis phenotype

Toward integrated historical climate research: the example of Atmospheric Circulation Reconstructions over the Earth

Climate change has become a key environmental narrative of the 21st century. However, emphasis on the science of climate change has overshadowed studies focusing on human interpretations of climate history, of adaptation and resilience, and of explorations of the institutions and cultural coping strategies that may have helped people adapt to climate changes in the past. Moreover, although the idea of climate change has been subject to considerable scrutiny by the physical sciences, recent climate scholarship has highlighted the need for a re examination of the cultural and spatial dimensions of climate, with contributions from the humanities and social sciences. Establishing a multidisciplinary dialogue and approach to climate research past, present, and future has arguably never been more important. This article outlines developments in historical climatology research and considers examples of integrated multidisciplinary approaches to climate, climatic variability, and climate change research, conducted across the physical sciences, social sciences, humanities, and the arts. We highlight the international Atmospheric Circulation Reconstructions over the Earth (ACRE) initiative as one example of such an integrated approach. Initially, ACRE began as a response from climate science to the needs of the agricultural sector in Queensland, Australia for a longer, more spatially, and temporally-complete database of the weather. ACRE has now evolved to embrace an international group of researchers working together across disciplines to integrate their efforts into a four-dimensional (4D) dynamical global historical climate-quality reanalysis (reconstruction). WIREs Clim Change 2016, 7:164–174. doi:10.1002/wcc.37

Testing the potential of a virtual reality neurorehabilitation system during performance of observation, imagery and imitation of motor actions recorded by wireless functional near-infrared spectroscopy (fNIRS)

Background Several neurorehabilitation strategies have been introduced over the last decade based on the so-called simulation hypothesis. This hypothesis states that a neural network located in primary and secondary motor areas is activated not only during overt motor execution, but also during observation or imagery of the same motor action. Based on this hypothesis, we investigated the combination of a virtual reality (VR) based neurorehabilitation system together with a wireless functional near infrared spectroscopy (fNIRS) instrument. This combination is particularly appealing from a rehabilitation perspective as it may allow minimally constrained monitoring during neurorehabilitative training. Methods fNIRS was applied over F3 of healthy subjects during task performance in a virtual reality (VR) environment: 1) 'unilateral' group (N = 15), contralateral recording during observation, motor imagery, observation & motor imagery, and imitation of a grasping task performed by a virtual limb (first-person perspective view) using the right hand; 2) 'bilateral' group (N = 8), bilateral recording during observation and imitation of the same task using the right and left hand alternately. Results In the unilateral group, significant within-condition oxy-hemoglobin concentration Δ[O2Hb] changes (mean ± SD μmol/l) were found for motor imagery (0.0868 ± 0.5201 μmol/l) and imitation (0.1715 ± 0.4567 μmol/l). In addition, the bilateral group showed a significant within-condition Δ[O2Hb] change for observation (0.0924 ± 0.3369 μmol/l) as well as between-conditions with lower Δ[O2Hb] amplitudes during observation compared to imitation, especially in the ipsilateral hemisphere (p < 0.001). Further, in the bilateral group, imitation using the non-dominant (left) hand resulted in larger Δ[O2Hb] changes in both the ipsi- and contralateral hemispheres as compared to using the dominant (right) hand. Conclusions This study shows that our combined VR-fNIRS based neurorehabilitation system can activate the action-observation system as described by the simulation hypothesis during performance of observation, motor imagery and imitation of hand actions elicited by a VR environment. Further, in accordance with previous studies, the findings of this study revealed that both inter-subject variability and handedness need to be taken into account when recording in untrained subjects. These findings are of relevance for demonstrating the potential of the VR-fNIRS instrument in neurofeedback applications

Using fMRI to investigate the potential cause of inverse oxygenation reported in fNIRS studies of motor imagery

© 2019 Elsevier B.V. Motor imagery (MI) is a commonly used cognitive task in brain–computer interface (BCI) applications because it produces reliable activity in motor-planning regions. However, a number of functional near-infrared spectroscopy (fNIRS) studies have reported the unexpected finding of inverse oxygenation: increased deoxyhemoglobin and decreased oxyhemoglobin during task periods. This finding questions the reliability of fNIRS for BCI applications given that MI activation should result in a focal increase in blood oxygenation. In an attempt to elucidate this phenomenon, fMRI and fNIRS data were acquired on 15 healthy participants performing a MI task. The fMRI data provided global coverage of brain activity, thus allowing visualization of all potential brain regions activated and deactivated during task periods. Indeed, fMRI results from seven subjects included activation in the primary motor cortex and/or the pre-supplementary motor area during the rest periods in addition to the expected activation in the supplementary motor and premotor areas. Of these seven subjects, two showed inverse oxygenation with fNIRS. The proximity of the regions showing inverse oxygenation to the motor planning regions suggests that inverse activation detected by fNIRS may likely be a consequence of partial volume errors due to the sensitivity of the optodes to both primary motor and motor planning regions

Consideration of a New Definition of Clinically Relevant Myocardial Infarction After Coronary Revascularization An Expert Consensus Document From the Society for Cardiovascular Angiography and Interventions (SCAI)

Numerous definitions have been proposed for the diagnosis of myocardial infarction (MI) after coronary revascularization. The universal definition for MI designates post procedural biomarker thresholds for defining percutaneous coronary intervention (PCI)-related MI (type 4a) and coronary artery bypass grafting (CABG)-related MI (type 5), which are of uncertain prognostic importance. In addition, for both the MI types, cTn is recommended as the biomarker of choice, the prognostic significance of which is less well validated than CK-MB. Widespread adoption of a MI definition not clearly linked to subsequent adverse events such as mortality or heart failure may have serious consequences for the appropriate assessment of devices and therapies, may affect clinical care pathways, and may result in misinterpretation of physician competence. Rather than using an MI definition sensitive for small degrees of myonecrosis (the occurrence of which, based on contemporary large-scale studies, are unlikely to have important clinical consequences), it is instead recommended that a threshold level of biomarker elevation which has been strongly linked to subsequent adverse events in clinical studies be used to define a &quot;clinically relevant MI.&quot; The present document introduces a new definition for &quot;clinically relevant MI&quot; after coronary revascularization (PCI or CABG), which is applicable for use in clinical trials, patient care, and quality outcomes assessment. Numerous definitions for the diagnosis of MI after coronary revascularization are in use (1). A standardized MI definition would provide uniformity for comparing clinical trial results, for assessing patient outcomes and for guiding quality improvement initiatives. In 2007, a &quot;universal definition&quot; for MI following coronary revascularization was proposed (2) and recently revised in 2012 (3). In this document, a PCI-related MI (type 4a) was defined as an increase in cTn to &gt;5Â the 99th percentile of the URL during the first 48 h following PCI (in patients with normal baseline cTn concentrations), plus either: 1) evidence of prolonged ischemia as demonstrated by prolonged chest pain; or 2) ischemic ST-segment changes or new pathological Q waves; or 3) angiographic evidence of a flow limiting complication; or 4) imaging evidence of new loss of viable myocardium or new regional wall motion abnormality. MI associated with CABG (type 5) was defined as an increase in cTn to &gt;10Â the 99th percentile URL during the first 48 h following CABG (in patients with normal baseline cTn concentrations), plus either: 1) new pathological Q waves or new LBBB; or 2) angiographically documente

Neurofeedback Using Real-Time Near-Infrared Spectroscopy Enhances Motor Imagery Related Cortical Activation

Accumulating evidence indicates that motor imagery and motor execution share common neural networks. Accordingly, mental practices in the form of motor imagery have been implemented in rehabilitation regimes of stroke patients with favorable results. Because direct monitoring of motor imagery is difficult, feedback of cortical activities related to motor imagery (neurofeedback) could help to enhance efficacy of mental practice with motor imagery. To determine the feasibility and efficacy of a real-time neurofeedback system mediated by near-infrared spectroscopy (NIRS), two separate experiments were performed. Experiment 1 was used in five subjects to evaluate whether real-time cortical oxygenated hemoglobin signal feedback during a motor execution task correlated with reference hemoglobin signals computed off-line. Results demonstrated that the NIRS-mediated neurofeedback system reliably detected oxygenated hemoglobin signal changes in real-time. In Experiment 2, 21 subjects performed motor imagery of finger movements with feedback from relevant cortical signals and irrelevant sham signals. Real neurofeedback induced significantly greater activation of the contralateral premotor cortex and greater self-assessment scores for kinesthetic motor imagery compared with sham feedback. These findings suggested the feasibility and potential effectiveness of a NIRS-mediated real-time neurofeedback system on performance of kinesthetic motor imagery. However, these results warrant further clinical trials to determine whether this system could enhance the effects of mental practice in stroke patients

Changes in Cerebral Hemodynamics during Complex Motor Learning by Character Entry into Touch-Screen Terminals

Introduction Studies of cerebral hemodynamics during motor learning have mostly focused on neurorehabilitation interventions and their effectiveness. However, only a few imaging studies of motor learning and the underlying complex cognitive processes have been performed. Methods We measured cerebral hemodynamics using near-infrared spectroscopy (NIRS) in relation to acquisition patterns of motor skills in healthy subjects using character entry into a touchscreen terminal. Twenty healthy, right-handed subjects who had no previous experience with character entry using a touch-screen terminal participated in this study. They were asked to enter the characters of a randomly formed Japanese syllabary into the touchscreen terminal. All subjects performed the task with their right thumb for 15 s alternating with 25 s of rest for 30 repetitions. Performance was calculated by subtracting the number of incorrect answers from the number of correct answers, and gains in motor skills were evaluated according to the changes in performance across cycles. Behavioral and oxygenated hemoglobin concentration changes across task cycles were analyzed using Spearman\u27s rank correlations. Results Performance correlated positively with task cycle, thus confirming motor learning. Hemodynamic activation over the left sensorimotor cortex (SMC) showed a positive correlation with task cycle, whereas activations over the right prefrontal cortex (PFC) and supplementary motor area (SMA) showed negative correlations. Conclusions We suggest that increases in finger momentum with motor learning are reflected in the activity of the left SMC. We further speculate that the right PFC and SMA were activated during the early phases of motor learning, and that this activity was attenuated with learning progress

Test–retest reliability of brain mitochondrial cytochrome-c-oxidase assessed by functional near-infrared spectroscopy

Functional near-infrared spectroscopy (fNIRS) is a noninvasive method for measuring in vivo both hemodynamic and mitochondrial metabolic activities in brain cortical structures. Although the test–retest reliability of the hemodynamic measures, such as reflected by oxygenated (HbO2), deoxygenated (HHb) hemoglobin, and the tissue oxygenation index (TOI), has been previously reported to be good to excellent, the reliability of the metabolic signal indexed by oxidized cytochrome-c-oxidase (oxCCO) has not been reported. The present test–retest study compared the reliability of the metabolic and hemodynamic signals in 10 healthy participants undergoing hypo- and hypercapnia challenges. The primary reliability measure was the intraclass correlation coefficient (ICC). Results of both hypo- and hypercapnia showed that the oxCCO signal (ICC  =  0.876  /  0.757) had robust reliability comparable with that of the HbO2 (ICC  =  0.841  /  0.801), HHb (ICC  =  0.804  /  0.571), and TOI (ICC  =  0.574  /  0.614) signals. These findings show that the oxCCO signal can be assessed by fNIRS with comparable reliability to the hemodynamic measures. We discuss the results in light of current interest in a mitochondrial metabolic marker derived from fNIRS