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.

Orbitofrontal Lesion Alters Brain Dynamics of Emotion-Attention and Emotion-Cognitive Control Interaction in Humans.

Patients with lesion to the orbitofrontal cortex (OFC) experience challenges in emotional control and emotion-guided behaviors. The OFC is known to participate in executive functions and attentional control of emotion and our previous research suggests OFC lesion alters the balance between voluntary and involuntary attention and cognitive control within the context of emotion. To better understand how OFC lesion affects the dynamics and interaction of these functions, we studied EEG and performance of 12 patients with lesion to the OFC and 11 control subjects with intact OFC in a Go/NoGo visual reaction time (RT) task with neutral targets and intervening threat-related emotional distractors (Executive RT Test). Event-related potentials (ERPs), specifically N2P3 peak-to-peak amplitude and the following late positive potential (LPP), were used to measure allocation of attention and cognitive control to emotional distractors. Task performance and Behavior Rating Inventory of Executive Functions-Adult version (BRIEF-A) scores were used to assess executive functions. As expected, the Control group showed increased N2P3 amplitude in the context of threat-related distractors, particularly over the right hemisphere, while LPP was not modulated by these distractors. In contrast, patients with OFC lesion showed no such impact of threat-related distractors on N2P3 amplitude but exhibited increased and prolonged left-lateralized impact of threat on LPP in the Go-condition. In NoGo-condition, the N2P3 amplitude was increased in both groups due to threat, but the impact was seen earlier, i.e., at the N2 peak in the OFC group and later at the P3 peak in Controls. The OFC group committed more errors in the Executive RT Test and reported more problems in BRIEF-A, thus both objective and subjective evidence for challenges in executive functions was obtained in patients with orbitofrontal lesion. Furthermore, the time-course of attention allocation and cognitive control towards task-irrelevant emotional stimuli was altered as evidenced by ERPs. We conclude that orbitofrontal lesion is associated with altered neural dynamics underlying the interaction of involuntary attention to emotion and cognitive control. These alterations in brain dynamics may underlie some of the challenges patients encounter in everyday life when emotional events interact with cognitive demands.

Greater Attention to Task-Relevant Threat Due to Orbitofrontal Lesion.

Injury to the orbitofrontal cortex (OFC) is a frequent consequence of head injury and may lead to dysfunctional regulation of emotional and social behavior. Dysfunctional emotional behavior may partly be related to the role of the OFC in emotion-attention interaction, as reported previously. In order to better understand its role in emotion-attention and emotion-cognitive control interactions, we investigated attention allocation to task-relevant and task-irrelevant threat-related emotional stimuli during a task requiring cognitive control in patients with lesion to the OFC. We measured the behavioral performance and event-related potentials (ERP) of 13 patients with OFC lesion and 11 control subjects during a Go/NoGo visual discrimination task. In the task, line drawings of threatening (spider) and neutral (flower) figures served as either task-relevant Go or NoGo signals, or as task-irrelevant distractors. Overall performance did not differ between the groups. In contrast to the control group performance, the orbitofrontal group performance was improved by relevant threat signal in comparison with neutral signal. Further, task-relevant threat signals evoked larger frontocentral N2-P3 amplitude in the orbitofrontal group. Taken together, behavioral and electrophysiological results suggest that patients with OFC injury allocated more attentional and cognitive control resources in the context of task-relevant emotional stimuli. This study provides new evidence for the role of the OFC in emotion-attention and emotion-cognitive control interactions. Further, the OFC seems to contribute to the balance between voluntary and involuntary attention networks in context of emotional stimuli. Better understanding of alterations in emotion-attention interaction offers insight into affective dysfunction due to OFC lesion.

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.