Impulsivity and Concussion in Juvenile Rats: Examining Molecular and Structural Aspects of the Frontostriatal Pathway

Abstract

Impulsivity and poor executive control have been implicated in the pathogenesis of many developmental and neuropsychiatric disorders. Similarly, concussions/mild traumatic brain injuries (mTBI) have been associated with increased risk for neuropsychiatric disorders and the development of impulsivity and inattention. Researchers and epidemiologists have therefore considered whether or not concussions induce symptoms of attention-deficit/hyperactivity disorder (ADHD), or merely unmask impulsive tendencies that were already present. The purpose of this study was to determine if a single concussion in adolescence could induce ADHD-like impulsivity and impaired response inhibition, and subsequently determine if inherent impulsivity prior to a pediatric mTBI would exacerbate post-concussion symptomology with a specific emphasis on impulsive and inattentive behaviours. As these behaviours are believed to be associated with the frontostriatal circuit involving the nucleus accumbens (NAc) and the prefrontal cortex (PFC), the expression patterns of 8 genes (Comt, Drd2, Drd3, Drd4, Maoa, Sert, Tph1, and Tph2) from these two regions were examined. In addition, Golgi-Cox staining of medium spiny neurons in the NAc provided a neuroanatomical examination of mTBI-induced structural changes. The study found that a single early brain injury could induce impulsivity and impairments in response inhibition that were more pronounced in males. Interestingly, when animals with inherent impulsivity experienced mTBI, injury-related deficits were exacerbated in female animals. The single concussion increased dendritic branching, but reduced synaptic density in the NAc, and these changes were likely associated with the increase in impulsivity. Finally, mTBI-induced impulsivity was associated with modifications to gene expression that differed dramatically from the gene expression pattern associated with inherent impulsivity, despite very similar behavioural phenotypes. Our findings suggest the need to tailor treatment strategies for mTBI in light of an individual’s premorbid characteristics, given significant differences in molecular profiles of the frontostriatal circuits that depend upon sex and the etiology of the behavioural phenotype.

Let’s call the whole thing off: evaluating gender and sex differences in executive function

“…Mild traumatic brain (mTBI) injury in rats was also found to have complex effects on executive function that varied by sex. mTBI led to more impulsive errors in the 5CSRTT in control males; however, more impulsive errors were identified only in females when examining offspring from nutrient-restricted dams [114], indicating that early life environment can also establish a sexdependent risk profile for future insults.…”

“…In the PFC, it is primarily excitatory synapses that are targeted for elimination [136]. Synaptic pruning is a key developmental process, as deficits in synaptic function are linked to neurodevelopmental disorders [137,138] and executive function deficits [114]. Further, executive function deficits have been suggested to relate to more subtle changes in neural function or microstructure rather than gross changes in neuron number or morphology [138].…”

Modeling sports‐related mild traumatic brain injury in animals—A systematic review

“…Likewise, in individuals with CTE symptoms, similar phenotypic manifestations have been reported as the condition progresses (Omalu et al, ). Results from the studies assessed here indicate increased anxiety and impaired attention (Hehar, Yeates, Kolb, Esser, & Mychasiuk, ; Wang et al, ; Yamakawa, Salberg, et al, ). There was also a consistent depression‐like response to the forced swim task in mTBI groups, as evidenced by immobility and disinclination to swim (Salberg et al, ).…”

Anemia predicts lower white matter volume and cognitive performance in sickle and non‐sickle cell anemia syndrome

“…Studies in rodent models with early, prepubescent traumatic brain injuries have revealed sexually dimorphic remodeling that persists into adulthood, possibly due to differences in brain maturation trajectories . The onset of WM volume changes may be occurring outside of the critical period in female subjects allowing appropriate compensation for early damage .…”