Reduced Frontal Nogo-N2 With Uncompromised Response Inhibition During Transcutaneous Vagus Nerve Stimulation—More Efficient Cognitive Control?

We have previously shown invasive vagus nerve stimulation to improve attention and working memory and alter emotion-attention interaction in patients with refractory epilepsy, suggesting that VNS might be useful in the treatment of cognitive impairment. The current research focuses on whether non-invasive, transcutaneous vagus nerve stimulation (tVNS) has similar effects to VNS. Furthermore, we aimed to assess whether tVNS has an impact on cognitive control in general or on underlying brain physiology in a task that mimics everyday life demands where multiple executive functions are engaged while encountering intervening emotional stimuli. Event-related potentials (ERP) evoked in such a task, specifically centro-parietal P3 and frontal N2 were used as biomarkers for attention allocation and cognitive control required to carry out the task. A single-blinded, sham-controlled, within-subject study on healthy subjects (n = 25) was conducted using Executive Reaction Time Test (RT-test), a Go/NoGo task engaging multiple executive functions along with intervening threat-related distractors while EEG was recorded. tVNS at the left tragus and sham stimulation at the left ear lobe was alternately delivered throughout the task. To assess the impact of tVNS on neural activity underlying attention and cognitive control, centro-parietal P3 and frontal N2 peak amplitudes were measured in Go and NoGo conditions. Task performance was assessed with RTs and different error types reflecting cognitive control in general and distinct executive functions, such as working memory and response inhibition.No significant effects due to tVNS on performance in the Executive RT-test were observed. For N2 there was a main effect of stimulator status and a significant interaction of trial type (Go, NoGo) and stimulator status. Post hoc analysis revealed that tVNS resulted in a significant reduction of frontal N2 only in the NoGo condition. No significant effects were observed for P3 nor were there any effects of emotion. Diminished NoGo-N2 potential along with unaltered task performance during tVNS suggests fewer cognitive control resources were required to successfully withhold a prepotent response. Though caution is warranted, we suggest that tVNS may lead to more efficient neural processing with fewer resources needed for successful cognitive control, providing promise for its potential use in cognitive enhancement.Peer reviewe

Frontal Alpha Asymmetry, a Potential Biomarker for the Effect of Neuromodulation on Brain's Affective Circuitry-Preliminary Evidence from a Deep Brain Stimulation Study

Neuromodulation techniques targeting limbic circuits can be used to treat refractory psychiatric or neurological disorders. However, objective measure for the impact of neuromodulation on affective brain circuits is lacking. Deep brain stimulation at a key node of the limbic circuit, the anterior thalamic nuclei (ANT-DBS), is used to treat refractory epilepsy. While effective in reducing seizures, patients have reported subjective depressive symptoms as a side effect. In line with potential vulnerability to depression, we have previously shown ANT-DBS to increase attention allocation to threat evidenced by behavior and brain physiology. Rightward frontal alpha asymmetry with greater right hemispheric activation is thought to reflect brain physiology linked with depression and anxiety. To that end, we investigated whether high-frequency electric stimulation at ANT influences frontal alpha asymmetry. Furthermore, we explored the impact of DBS on emotional modulation of frontal alpha asymmetry and whether it is linked with emotional modulation of response speed. Electrical stimulation at ANT led to an increased rightward frontal alpha asymmetry compared to situations where stimulation was off (F ((1, 12)) = 14.09, p = 0.003) or the thalamic control location was stimulated (F ((1, 12)) = 10.19, p = 0.008), along with prolonged reaction times in the context of emotional distractors (F ((1,7)) = 16.66, p = 0.005). The change was specifically driven by increased activity in the right hemisphere. Furthermore, we found a correlation between the emotional modulation of frontal alpha asymmetry and emotional interference of response speed due to ANT stimulation (r = 0.78, p = 0.02). In conclusion, DBS at ANT increased relative right hemispheric activity and this was linked with emotional modulation of behavior. Previous studies have linked frontal alpha asymmetry with emotion related symptoms and furthermore, Vagus Nerve Stimulation (VNS) has been shown to modulate alpha asymmetry. Thus, in the light of the previous literature and the current findings, we suggest that frontal alpha asymmetry along with emotional interference of response speed might be a feasible biomarker for the effects of neuromodulation on brain's affective circuitry in general

Enhanced attention capture by emotional stimuli in mild traumatic brain injury

Mild traumatic brain injury (mTBI) may be associated with compromised executive functioning and altered emotional reactivity. Despite frequent affective and cognitive symptoms in mTBI, objective evidence for brain dysfunction is often lacking. Previously we have reported compromised performance in symptomatic mTBI patients in an executive reaction time (RT) test, a computer-based RT test engaging several executive functions simultaneously. Here, we investigated the cognitive control processes in mTBI in context of threat-related stimuli. We used behavioral measures and event-related potentials (ERP) to investigate attentional capture by task-relevant and task-irrelevant emotional stimuli during a Go-NoGo task requiring cognitive control. We also assessed subjective cognitive, somatic, and emotional symptoms with questionnaires. Twenty-seven subjects with previous mTBI and 17 controls with previous ankle injury participated in the study over 9 months post-injury. Electroencephalogram (EEG) was recorded while patients performed a modified executive RT-test. N2-P3 ERP component was used as a general measure of allocated attentional and executive processing resources. Although at the time of the testing, the mTBI and the control groups did not differ in symptom endorsement, mTBI patients reported having had more emotional symptoms overall since the injury than controls. The overall RT-test performance levels did not differ between groups. However, when threat-related emotional stimuli were used as Go-signals, the mTBI group was faster than the control group. In comparison to neutral stimuli, threat-related stimuli were associated with increased N2-P3 amplitude in all conditions. This threat-related enhancement of the N2-P3 complex was greater in mTBI patients than in controls in response to Go signals and NoGo signals, independent of relevance. We conclude that mTBI may be associated with enhanced attentional and executive resource allocation to threat-related stimuli. Along with behavioral evidence for enhanced attention allocation to threat stimuli, increased brain responses to threat were observed in mTBI. Enhanced attention capture by threat-related emotional stimuli may reflect inefficient top-down control of bottom-up influences of emotion, and might contribute to affective symptoms in mTBI.Fil: Exposito, Veronica. Tampere University Hospital; Finlandia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kuusinen, Venla. Tampere University Hospital; FinlandiaFil: Brause, Maarja. Tampere University Hospital; FinlandiaFil: Peräkylä, Jari. Tampere University Hospital; FinlandiaFil: Polvivaara, Markus. Tampere University Hospital; FinlandiaFil: Dos Santos Ribeiro, Rodolfo. Tampere University Hospital; FinlandiaFil: Öhman, Juha. Tampere University Hospital; FinlandiaFil: Hartikainen, Kaisa M.. Tampere University Hospital; Finlandi

Occupational Burnout Is Linked with Inefficient Executive Functioning, Elevated Average Heart Rate, and Decreased Physical Activity in Daily Life - Initial Evidence from Teaching Professionals

Burnout is becoming a global pandemic jeopardizing brain health, with a huge impact on quality of life, available workforce, and the economy. Knowledge of the impact of burnout on cognition, physiology, and physical activity (PA) in daily life allows for an improved understanding of the health consequences and everyday ramifications of burnout. Twenty-eight volunteers participated in a three-day recording of daily physiology and PA, including heart rate (HR) and daily steps, with a wearable device. They filled in questionnaires screening for burnout (BBI-15), depression (BDI), and executive functions (EFs) in daily life (BRIEF-A). The subjects with burnout had more challenges in EFs, higher average HRs and lower numbers of steps in daily life than those without it. The BBI-15 scores correlated positively with the BDI scores and BRIEF-A indices and negatively with the awake HR variability (HRV) and daily steps. The metacognition index correlated negatively with the HRV. In conclusion, burnout is linked with compromised EFs along with alterations in cardiac physiology and PA in daily life. Such alterations may be easily detected with wearable devices, opening possibilities for novel biomarkers of burnout and other neuropsychiatric disorders. We suggest that physical activity and heart and brain health are intimately intertwined and that burnout interacts with each of them bidirectionally.publishedVersionPeer reviewe

Chemical transformations in monoterpene-derived organic aerosol enhanced by inorganic composition

Secondary organic aerosol (SOA) is known to impact both climate and air quality, yet molecular-level composition measurements remain challenging, hampering our understanding of SOA formation and evolution. Here, we reveal the importance of underestimated reaction pathways for the (trans) formation of SOA from monoterpenes, one of the largest SOA precursors globally. Utilizing mass spectrometric techniques to achieve a comprehensive characterization of molecular-level changes in the SOA, we were able to link the appearance of high-molecular weight (HMW) organic molecules to the concentration and level of neutralization of particulate sulfate. Interestingly, this oligomerization coincided with a decrease of highly oxygenated molecules (HOMs). Our findings highlight the role of particle-phase processing, and the underestimated importance of sulfate aerosol for monoterpene-SOA formation. The observations of these processes directly in the atmosphere reveal the need to account for the formation of HMW oligomers to fully understand the physicochemical properties of organic aerosol.Peer reviewe

Evaluating the performance of five different chemical ionization techniques for detecting gaseous oxygenated organic species

The impact of aerosols on climate and air quality remains poorly understood due to multiple factors. One of the current limitations is the incomplete understanding of the contribution of oxygenated products, generated from the gas-phase oxidation of volatile organic compounds (VOCs), to aerosol formation. Indeed, atmospheric gaseous chemical processes yield thousands of (highly) oxygenated species, spanning a wide range of chemical formulas, functional groups and, consequently, volatilities. While recent mass spectrometric developments have allowed extensive on-line detection of a myriad of oxygenated organic species, playing a central role in atmospheric chemistry, the detailed quantification and characterization of this diverse group of compounds remains extremely challenging. To address this challenge, we evaluated the capability of current state-of-the-art mass spectrometers equipped with different chemical ionization sources to detect the oxidation products formed from alpha-Pinene ozonolysis under various conditions. Five different mass spectrometers were deployed simultaneously for a chamber study. Two chemical ionization atmospheric pressure interface time-of-flight mass spectrometers (CI-APi-TOF) with nitrate and amine reagent ion chemistries and an iodide chemical ionization time-of-flight mass spectrometer (TOF-CIMS) were used. Additionally, a proton transfer reaction time-of-flight mass spectrometer (PTR-TOF 8000) and a new "vocus" PTR-TOF were also deployed. In the current study, we compared around 1000 different compounds between each of the five instruments, with the aim of determining which oxygenated VOCs (OVOCs) the different methods were sensitive to and identifying regions where two or more instruments were able to detect species with similar molecular formulae. We utilized a large variability in conditions (including different VOCs, ozone, NOx and OH scavenger concentrations) in our newly constructed atmospheric simulation chamber for a comprehensive correlation analysis between all instruments. This analysis, combined with estimated concentrations for identified molecules in each instrument, yielded both expected and surprising results. As anticipated based on earlier studies, the PTR instruments were the only ones able to measure the precursor VOC, the iodide TOF-CIMS efficiently detected many semi-volatile organic compounds (SVOCs) with three to five oxygen atoms, and the nitrate CI-APi-TOF was mainly sensitive to highly oxygenated organic (O > 5) molecules (HOMs). In addition, the vocus showed good agreement with the iodide TOF-CIMS for the SVOC, including a range of organonitrates. The amine CI-APi-TOF agreed well with the nitrate CI-APi-TOF for HOM dimers. However, the loadings in our experiments caused the amine reagent ion to be considerably depleted, causing nonlinear responses for monomers. This study explores and highlights both benefits and limitations of currently available chemical ionization mass spectrometry instrumentation for characterizing the wide variety of OVOCs in the atmosphere. While specifically shown for the case of alpha-Pinene ozonolysis, we expect our general findings to also be valid for a wide range of other VOC-oxidant systems. As discussed in this study, no single instrument configuration can be deemed better or worse than the others, as the optimal instrument for a particular study ultimately depends on the specific target of the study.Peer reviewe

Emotional Modulation of Frontal Alpha Asymmetry - a Novel Biomarker of Mild Traumatic Brain Injury

Objective findings of brain injury or dysfunction are typically lacking in mild traumatic brain injury (MTBI) despite prolonged post-concussion symptoms in some patients. Thus, there is a need for objective biomarkers of MTBI that reflect altered brain physiology underlying subjective symptoms. We have previously reported increased attention to threat-related stimuli in subjects with MTBI, suggesting a physiological vulnerability to depression. Vulnerability to depression has been linked with relatively greater activity of the right than left frontal cortex reflected in inverse pattern in frontal alpha with greater power on the left than right. We investigated whether patients with previous MTBI show this pattern of frontal activity reflected in more negative frontal alpha asymmetry (FAA) scores. Furthermore, in search for potential biomarkers of MTBI, we created a novel index, emotional modulation of FAA (eFAA) and investigated whether it correlates with subjective symptoms. EEG was recorded while subjects with previous MTBI and controls performed a computer-based reaction time task integrating different cognitive executive functions and containing either threat-related or emotionally neutral visual stimuli. Post-concussion symptoms and depression were assessed using the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) and Beck's depression inventory (BDI). Task-induced FAA was assessed and eFAA calculated by subtracting FAA in the context of neutral stimuli from FAA in the context of emotional stimuli. The MTBI group showed FAA scores reflecting relatively greater right-sided frontal activity compared to healthy controls. eFAA differentiated the symptomatic MTBI from non-symptomatic MTBI group and from healthy controls. eFAA also correlated with RPQ and BDI scores. In conclusion, FAA pattern previously linked with vulnerability to depression, was observed in patients with previous MTBI. Furthermore, eFAA has potential as a biomarker of altered affective brain functions in MTBI

Altered neural processes underlying executive function in occupational burnout : Basis for a novel EEG biomarker

Introduction: As burnout has become a global pandemic, there is a call for improved understanding and detection of alterations in brain functions related to it. We have previously reported challenges in executive functions (EFs) in daily life, especially in metacognition, in subjects with occupational burnout, along with alterations in cardiac physiology. In the current study, we focused on the impact of burnout on brain physiology during a task requiring EF. Methods: Fifty-four volunteers filled in inventories of burnout, depression, and EF in daily life (BBI-15, BDI, and BRIEF-A). Based on the BBI-15 score, subjects were divided into burnout and non-burnout groups. Subjects performed a Go/NoGo test (Executive RT test) engaging several EFs, while their EEG was recorded. The inventory scores, cognitive performance scores, and event-related potential (N2, P3) amplitudes, latencies, and interpeak latencies (IPLs) were compared between the groups. Results: There were significant differences in the BDI and BRIEF-A scores between the groups, with more symptoms of depression and challenges in daily life in the burnout group. There were no differences in objective performance measures in the EF task between the groups. However, centroparietal P3 amplitude was larger, and while there were no differences in N2 or P3 latencies, N2-P3 IPL was longer in the Go condition in the burnout than in non-burnout group. Both ERP measures correlated significantly with burnout symptoms. A regression model from centroparietal P3 amplitude and N2-P3 IPL predicted significantly both the BBI-15 score and the BRIEF-A metacognition index. Discussion: We conclude that burnout is linked with challenges in EF in daily life and alterations in the underlying neural processes. While cognitive performance in the task was equal, electrophysiological measures differed between the groups. Prolonged N2-P3 IPL points toward slowed transition from one cognitive process to another. Increased P3 amplitude, on the other hand, reflects increased allocation of neural processing resources. This may be a compensatory mechanism, allowing for equal performance with controls. These electrophysiological measures, obtained during the EF task, show promise as brain physiology-based biomarkers of burnout, contributing to its improved and objective detection. In addition, these results indicate occupational burnout is linked with objective alterations in brain physiology.Peer reviewe

Human Brain Reacts to Transcranial Extraocular Light

Transcranial extraocular light affects the brains of birds and modulates their seasonal changes in physiology and behavior. However, whether the human brain is sensitive to extraocular light is unknown. To test whether extraocular light has any effect on human brain functioning, we measured brain electrophysiology of 18 young healthy subjects using event-related potentials while they performed a visual attention task embedded with emotional distractors. Extraocular light delivered via ear canals abolished normal emotional modulation of attention related brain responses. With no extraocular light delivered, emotional distractors reduced centro-parietal P300 amplitude compared to neutral distractors. This phenomenon disappeared with extraocular light delivery. Extraocular light delivered through the ear canals was shown to penetrate at the base of the scull of a cadaver. Thus, we have shown that extraocular light impacts human brain functioning calling for further research on the mechanisms of action of light on the human brain.Public Library of Science open acces

Systematically reviewing and synthesizing evidence from conversation analytic and related discursive research to inform healthcare communication practice and policy: an illustrated guide

Background Healthcare delivery is largely accomplished in and through conversations between people, and healthcare quality and effectiveness depend enormously upon the communication practices employed within these conversations. An important body of evidence about these practices has been generated by conversation analysis and related discourse analytic approaches, but there has been very little systematic reviewing of this evidence. Methods We developed an approach to reviewing evidence from conversation analytic and related discursive research through the following procedures: • reviewing existing systematic review methods and our own prior experience of applying these • clarifying distinctive features of conversation analytic and related discursive work which must be taken into account when reviewing • holding discussions within a review advisory team that included members with expertise in healthcare research, conversation analytic research, and systematic reviewing • attempting and then refining procedures through conducting an actual review which examined evidence about how people talk about difficult future issues including illness progression and dying Results We produced a step-by-step guide which we describe here in terms of eight stages, and which we illustrate from our ‘Review of Future Talk’. The guide incorporates both established procedures for systematic reviewing, and new techniques designed for working with conversation analytic evidence. Conclusions The guide is designed to inform systematic reviews of conversation analytic and related discursive evidence on specific domains and topics. Whilst we designed it for reviews that aim at informing healthcare practice and policy, it is flexible and could be used for reviews with other aims, for instance those aiming to underpin research programmes and projects. We advocate systematically reviewing conversation analytic and related discursive findings using this approach in order to translate them into a form that is credible and useful to healthcare practitioners, educators and policy-makers