Impact of Mild Traumatic Brain Injury and Orbitofrontal Cortex Lesion on Affective and Cognitive Brain Functions

Mild traumatic brain injury (MTBI) is sometimes called an invisible injury. While normally subjects with MTBI recover well, remarkably many suffer from prolonged symptoms despite intact imaging and neuropsychological test results. A similar discrepancy between subjective cognitive and affective complaints and challenges in daily life, but intact neuropsychological test results are frequently encountered in patients with orbitofrontal cortex (OFC) lesion. The OFC has an important role in integrating emotional information into appropriate actions, with lesion to the OFC causing deficits in these processes. Symptoms and challenges related to alterations in emotion guided behaviors, emotion regulation, attention and executive functions (EFs) are common after MTBI and OFC injury, however, the underlying neural mechanisms predisposing to them remain unclear.
In this thesis, we aimed to better understand the neural mechanisms underlying affective and cognitive symptoms in MTBI and OFC injury. We also aimed at unraveling the role of intact OFC in the interplay between emotion and attention and the impact of OFC lesion and MTBI on it. In addition, we aimed to develop a novel electroencephalography (EEG) based biomarker of MTBI.

Subjects with MTBI (n = 27) and OFC lesion (n = 16) were included in the studies along with healthy control subjects. We used event-related potentials (ERPs) and frontal alpha asymmetry (FAA) to study injury-related alterations in brain physiology underlying emotion-attention interaction and cognitive control. EEG was recorded during a cognitive task (Executive RT Test), where threatening and neutral stimuli (task-relevant or irrelevant) were embedded into a Go-NoGo task. We assessed whether attention and cognitive control -related ERP components (N2, P3, N2P3) and task-performance differed between subjects with MTBI or OFC lesion and healthy controls. We further evaluated whether task-induced FAA and a novel index, emotional modulation of FAA (eFAA), reflect post-concussion symptoms (PCS) after MTBI. Self-report questionnaires of PCS, depression symptoms and EFs in daily life were collected to study correlations between symptom scores and objective physiological measures.

The MTBI group reported more emotional symptoms than control subjects. They also had larger N2P3 ERP amplitudes in context of task-relevant threat in the Go-condition coupled with faster reaction times. In the NoGo-condition, larger N2P3 amplitudes were detected both in context of task-relevant and task-irrelevant threat in the MTBI group, and more errors were committed with task-irrelevant threat. Further, rightward FAA i.e., relatively more activity on the right compared to the left frontal regions, a pattern associated with vulnerability to depression was observed in subjects with MTBI. eFAA distinguished subjects with MTBI and prolonged PCS from those without symptoms and from controls. Moreover, the eFAA obtained during the Executive RT Test was negatively correlated with subjective reports of depressive and post-concussion symptoms.

The OFC group exhibited larger N2P3 amplitudes in context with task-relevant threat in both Go- and NoGo-conditions. In contrast, when confronted with threat stimuli that were presented only as task-irrelevant distractors, they didn’t display an initial N2P3 increase but demonstrated pronounced late positive waves, indicative of emotional processing. The OFC group had generally worse task-performance when the task included emotional stimuli only as task-irrelevant distractors, whereas their task-performance seemed to slightly benefit from task-relevant threat. The OFC group also reported more challenges in EFs and more PCS than controls.

To summarize, we detected alterations in interactions of affective, attentional and EF processing after MTBI and OFC lesion. Subjects with MTBI allocated more attention to both task-irrelevant and task-relevant threat than controls while subjects with OFC lesion allocated more attention particularly to task-relevant threat. Alterations in attention to threat may contribute to emotional symptoms and vulnerability to depression in MTBI. We suggest the observed alterations reflect disruption of frontal-subcortical circuits subserving emotion-cognition interactions. The OFC is important in balancing voluntary and involuntary attention, especially in gearing attention to task-irrelevant emotion. Lesion to the OFC leads to challenges in swift allocation of attention to task-irrelevant but emotionally relevant stimuli. This may underlie some of the daily challenges experienced after OFC lesion, where timely evaluation of emotional stimuli and its appropriate integration into actions is crucial.

The results of this thesis shed new light on the role of OFC in attention to emotion and on the possible mechanisms of prolonged symptoms after MTBI. Finally, we introduce a novel biomarker for MTBI, known as eFAA, reflecting alterations in affective and cognitive brain circuits and functions due to brain injury.