A Role for the Amygdala in Impairments of Affective Behaviors Following Mild Traumatic Brain Injury

Abstract

Mild traumatic brain injury (TBI) results in chronic affective disorders such as depression, anxiety, and fear that persist up to years following injury and significantly impair the quality of life for patients. Although a great deal of research has contributed to defining symptoms of mild TBI, there are no adequate drug therapies for brain-injured individuals. Preclinical studies have modeled these deficits in affective behaviors post-injury to understand the underlying mechanisms with a view to developing appropriate treatment strategies. These studies have also unveiled sex differences that contribute to the varying phenotypes associated with each behavior. Although clinical and preclinical studies have viewed these behavioral deficits as separate entities with unique neurobiological mechanisms, mechanistic similarities suggest that a novel approach is needed to advance research on drug therapy. This review will discuss the circuitry involved in the expression of deficits in affective behaviors following mild TBI in humans and animals and provide evidence that the manifestation of impairment in these behaviors stems from an amygdala-dependent emotional processing deficit. It will highlight mechanistic similarities between these different types of affective behaviors that can potentially advance mild TBI drug therapy by investigating treatments for the deficits in affective behaviors as one entity, requiring the same treatment.

Life after mild traumatic brain injury: Widespread structural brain changes associated with psychological distress revealed with multimodal magnetic resonance imaging

“…Results showed an association between increased amygdala thickness and psychological distress symptoms post TBI. This confirms previous findings that link amygdala increased connectivity and activation to impairment in memory, attention and learning on a cognitive level, as well as to depression, anxiety and fear-related behaviors on the emotional domain [60].…”

Measuring Anxiety-Like Behaviors in Rodent Models of Traumatic Brain Injury

“…The authors reported that only about 13% of the injured animals were found to be "vulnerable, " showing increased exploration of anxiogenic regions during testing compared to baseline behavior and to sham-treated animals (Popovitz et al, 2021). The behavior of the vulnerable mice had neurobiological correlates in the medial prefrontal cortex, basolateral amygdala, and ventral hippocampus; all areas that are associated with stress and anxiety (Almeida-Suhett et al, 2014;Bryant and Barker, 2020;Kenwood et al, 2021;Liu et al, 2021;McCorkle et al, 2021;Pentkowski et al, 2021). Statz et al employed a different "affective profiling" technique to identify "affected" and "unaffected" rats 3 weeks or 6 months following exposure to repeated blast overpressure (Statz et al, 2019).…”

Traumatic brain injury-induced fear generalization in mice involves hippocampal memory trace dysfunction and is alleviated by (R,S)-ketamine

“…Finally, we quantified memory traces in two subregions of the AMG, the BA and CeA, as these are the two primary subregions of the AMG that are essential for expression of fear ( Figures 3A-C ) [31-32]. In the BA, there were no significant differences in the number of EYFP + ( Figure 3D ) or c-fos + ( Figure 3E ) cells between the groups.…”