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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. [ABSTRACT FROM AUTHOR]

Background: Alterations in executive functions, emotion regulation, and their interaction are common concomitants of depression. Executive dysfunction frequently lingers after treatment, has adverse effects on daily life, and predisposes to recurrence of depression. Yet, sensitive measures of executive function for reliable assessment of cognitive outcomes are still lacking in clinical practice. To better understand the impact of depression and its most effective treatment, electroconvulsive therapy (ECT), on cognition, we assessed executive functions pre- and post-ECT and whether objective measures reflecting alterations in emotion–executive function interaction correlate with depression severity or with cognitive outcome. Methods: Executive functions were assessed in 21 patients with major depressive disorder (MDD) before and after ECT using subjective measures from the Behavior Rating Inventory of Executive Function—Adult version (BRIEF-A) and objective cognitive performance measures derived from computer-based test of executive function, Executive Reaction Time (RT) Test. In addition, we created novel indices reflecting emotional modulation of cognitive performance by subtracting different performance measures in the context of neutral distractors from those in the context of threat-related distractors. We correlated these indices with Beck Depression Inventory (BDI) and BRIEF-A scores. Results: Depression was significantly alleviated, and executive functions improved post-ECT, as seen in reduced BDI scores, BRIEF-A scores, and number of errors in Executive RT Test. Pre-ECT BDI scores correlated with threat modulation of RT (tmRT) and threat modulation of working memory (tmWM). Post-ECT tmRT correlated with several Behavioral Regulation scales and tmWM with several Metacognition scales of BRIEF-A. Conclusion: While caution is warranted, results from both subjective and objective measures suggest that ECT significantly improves executive functions and emotion regulation along with alleviation of depression. Novel indices derived from threat modulation of executive function and working memory show promise as objective biomarkers of depression severity pre-ECT and cognitive outcome post-ECT with potential for guiding depression treatments. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Deep brain stimulation (DBS) of anterior thalamic nuclei (ANT) is a novel promising therapeutic method for treating refractory epilepsy. Despite reports of subjective memory impairments and mood disturbances in patients with ANT–DBS, little is known of its effects on cognitive and affective processes. Hypothesis: The anterior thalamus has connections to prefrontal and limbic networks important for cognitive control and emotional reactivity. More specifically, anterior cingulate cortex (ACC), linked with ANT, has been assigned roles related to response inhibition and attention allocation to threat. Thus, we hypothesized ANT–DBS to influence executive functions, particularly response inhibition, and modulate emotional reactivity to threat. Method: Twelve patients having undergone ANT–DBS for intractable epilepsy participated in the study. Patients performed a computer-based executive reaction time (RT) test—that is, a go/no-go visual discrimination task with threat-related emotional distractors and rule switching, while the DBS was switched ON (5/5 mA constant current) and OFF every few minutes. Results: ANT–DBS increased the amount of commission errors—that is, errors where subjects failed to withhold from responding. Furthermore, ANT–DBS slowed RTs in context of threat-related distractors. When stimulation was turned off, threat-related distractors had no distinct effect on RTs. Conclusion: We found immediate objective effects of ANT–DBS on human cognitive control and emotion–attention interaction. We suggest that ANT–DBS compromised response inhibition and enhanced attention allocation to threat due to altered functioning of neural networks that involve the DBS-target, ANT, and the regions connected to it such as ACC. The results highlight the need to consider affective and cognitive side-effects in addition to the therapeutic effect when adjusting stimulation parameters. Furthermore, this study introduces a novel window into cognitive and affective processes by modulating the associative and limbic networks with direct stimulation of key nodes in the thalamus. [ABSTRACT FROM AUTHOR]

Hemispheric asymmetries in affective and cognitive functions have been extensively studied. While both cerebral hemispheres contribute to most affective and cognitive processes, neuroscientific literature and neuropsychological evidence support an overall right hemispheric dominance for emotion, attention and arousal. Emotional stimuli, especially those with survival value such as threat, tend to be prioritized in attentional resource competition. Arousing unpleasant emotional stimuli have prioritized access, especially to right-lateralized attention networks. Interference of task performance may be observed when limited resources are exhausted by task- and emotion-related processing. Tasks that rely on right hemisphere-dependent processing, like attending to the left visual hemifield or global-level visual features, are especially vulnerable to interference due to attention capture by unpleasant emotional stimuli. The aim of this review is to present literature regarding the special role of the right hemisphere in affective and attentional brain processes and their interaction. Furthermore, clinical and technological implications of this interaction will be presented. Initially, the effects of focal right hemisphere lesion or atrophy on emotional functions will be introduced. Neurological right hemisphere syndromes including aprosodia, anosognosia and neglect, which further point to the predominance of the intact right hemisphere in emotion, attention and arousal will be presented. Then there will be a brief review of electrophysiological evidence, as well as evidence from patients with neglect that support attention capture by emotional stimuli in the right hemisphere. Subsequently, experimental work on the interaction of emotion, attention and cognition in the right hemispheres of healthy subjects will be presented. Finally, clinical implications for better understanding and assessment of alterations in emotion–attention interaction due to brain disorder or treatment, such as neuromodulation, that impact affective brain functions will be discussed. It will be suggested that measuring right hemispheric emotion–attention interactions may provide basis for novel biomarkers of brain health. Such biomarkers allow for improved diagnostics in brain damage and disorders and optimized treatments. To conclude, future technological applications will be outlined regarding brain physiology-based measures that reflect engagement of the right hemisphere in affective and attentional processes. [ABSTRACT FROM AUTHOR]

Patients treated with deep brain stimulation (DBS) provide an opportunity to study affective processes in humans with “lesion on demand” at key nodes in the limbic circuitries, such as at the anterior thalamic nuclei (ANT). ANT has been suggested to play a role in emotional control with its connection to the orbitofrontal cortex and the anterior cingulate cortex. However, direct evidence for its role in emotional function in human subjects is lacking. Reported side effects of ANT–DBS in the treatment of refractory epilepsy include depression related symptoms. In line with these mood-related clinical side effects, we have previously reported that stimulating the anterior thalamus increased emotional interference in a visual attention task as indicated by prolonged reaction times due to threat-related emotional distractors. We used event-related potentials to investigate potential attentional mechanism behind this behavioural observation. We hypothesized that ANT–DBS leads to greater attention capture by threat-related distractors. We tested this hypothesis using centro-parietal N2–P3 peak-to-peak amplitude as a measure of allocated attentional resources. Six epileptic patients treated with deep brain stimulation at ANT participated in the study. Electroencephalography was recorded while the patients performed a computer based Executive-Reaction Time test with threat-related emotional distractors. During the task, either ANT or a thalamic control location was stimulated, or the stimulation was turned off. Stimulation of ANT was associated with increased centro-parietal N2–P3 amplitude and increased reaction time in the context of threat-related emotional distractors. We conclude that high frequency electric stimulation of ANT leads to greater attentional capture by emotional stimuli. This is the first study to provide direct evidence from human subjects with on-line electric manipulation of ANT for its role in emotion–attention interaction. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]