The Behavioral Neuroscience of Traumatic Brain Injury.

Traumatic brain injury is a calamity of various causes, pathologies, and extremely varied and often complex clinical presentations. Because of its predilection for brain systems underlying cognitive and complex behavioral operations, it may cause chronic and severe psychiatric illness that requires expert management. This is more so for the modern epidemic of athletic and military brain injuries which are dominated by psychiatric symptoms. Past medical, including psychiatric, history, and comorbidities are important and relevant for formulation and management. Traumatic brain injury is a model for other neuropsychiatric disorders and may serve as an incubator of new ideas for neurodegenerative disease.

The p53 inactivators pifithrin-µ and pifithrin-α mitigate TBI-induced neuronal damage through regulation of oxidative stress, neuroinflammation, autophagy and mitophagy.

Traumatic brain injury (TBI) is one of the most common causes of death and disability worldwide. We investigated whether inhibition of p53 using pifithrin (PFT)-α or PFT-µ provides neuroprotective effects via p53 transcriptional dependent or -independent mechanisms, respectively. Sprague Dawley rats were subjected to controlled cortical impact TBI followed by the administration of PFTα or PFT-µ (2 mg/kg, i.v.) at 5 h after TBI. Brain contusion volume, as well as sensory and motor functions were evaluated at 24 h after TBI. TBI-induced impairments were mitigated by both PFT-α and PFT-µ. Fluoro-Jade C staining was used to label degenerating neurons within the TBI-induced cortical contusion region that, together with Annexin V positive neurons, were reduced by PFT-µ. Double immunofluorescence staining similarly demonstrated that PFT-µ significantly increased HO-1 positive neurons and mRNA expression in the cortical contusion region as well as decreased numbers of 4-hydroxynonenal (4HNE)-positive cells. Levels of mRNA encoding for p53, autophagy, mitophagy, anti-oxidant, anti-inflammatory related genes and proteins were measured by RT-qPCR and immunohistochemical staining, respectively. PFT-α, but not PFT-µ, significantly lowered p53 mRNA expression. Both PFT-α and PFT-µ lowered TBI-induced pro-inflammatory cytokines (IL-1ß and IL-6) mRNA levels as well as TBI-induced autophagic marker localization (LC3 and p62). Finally, treatment with PFT-µ mitigated TBI-induced declines in mRNA levels of PINK-1 and SOD2. Our data suggest that both PFT-µ and PFT-α provide neuroprotective actions through regulation of oxidative stress, neuroinflammation, autophagy, and mitophagy mechanisms, and that PFT-µ, in particular, holds promise as a TBI treatment strategy.

Relationships between executive function, working memory, and decision-making on the Iowa Gambling Task: Evidence from ventromedial patients, dorsolateral patients, and normal subjects.

The results of previous studies are inconsistent in regard to the relationship between the Iowa Gambling Task (IGT), working-memory (WM), and executive tasks, and whether these cognitive processes could be considered as mechanisms underlying a decision-making deficit. Moreover, the relationship between the IGT and executive measures is examined based on a limited number of executive tasks, within different populations showing diffuse damage. In addition, there are fewer studies carried out within control participants, with those studies also being inconclusive. It is also suggested that the association of the IGT performance with executive tasks depends on whether the IGT was running under ambiguity or under risk. In this work, all of these issues are studied. Results showed that both patients with ventromedial (VMPFC, N = 10) and dorsolateral (DLPFC, N = 10) prefrontal cortex lesions are significantly impaired on almost all executive tasks, WM tasks, and the IGT. Furthermore, when the IGT is run under risk, there are significant correlations between executive measures and the IGT for the DLPFC patients and the control participants (N = 34) but not the VMPFC patients. No correlation was found between WM tasks and the IGT for both frontal subgroups and control participants. These findings suggested that the mechanisms underlying the IGT deficit differ according to the lesion locations.

Exploring the factor structure of a battery of neuropsychological assessments among the CENC cohort.

OBJECTIVE: The goal of the Chronic Effects of Neurotrauma Consortium (CENC) study is to explore the effects of concussions among Service Members and Veterans. A factor model was fit to selected neuropsychological measures to identify potentially useful relationships between assessments collected on CENC-enrolled participants. METHOD: 492 post-9/11 participants with combat exposure were enrolled across four VA study sites. Participants completed assessments including concussion history, neurocognitive functioning, and self-report questionnaires. Exploratory factor analyses (EFA) using four different methods with varimax and promax rotations were used to analyse the cognitive variables. Final model selection was based on factor loadings towards simple structure. RESULTS: The scree plot suggested the number of factors to be extracted was between 4 and 5. EFA produced a 5-factor MINRES model with promax rotation that resulted in a factor loading with variables loading on only one factor with a predefined threshold (0.40). Variables loaded on five cognition domains: list learning, working memory/executive skills, cognitive control, fluency, and memory. CONCLUSION: These results provide reasonable evidence that data collected from the CENC neuropsychological battery can be reduced to five clinically useful factors. This will enable us to use the factors for further study of the impact of concussion on neurodegeneration.

Cognitive Outcomes of Patients with Traumatic Bifrontal Contusions.

OBJECTIVES: We aimed to investigate the prevalence and pattern of cognitive dysfunction in patients with traumatic bifrontal contusions and their association with functional outcome. MATERIALS AND METHODS: We prospectively recruited patients with bifrontal contusions in a regional neurosurgical center in Hong Kong over a 2-year period. Functional outcome was assessed by modified Rankin Scale (mRS), and cognitive outcomes were assessed by Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and a comprehensive neuropsychological battery. RESULTS: We recruited 34 patients with traumatic bifrontal contusions over a 2-year period. Nine (26%) patients had craniotomy for evacuation of left or right frontal contusions. Functional outcome using mRS was significantly correlated with cognitive outcomes using MMSE or MoCA. The effect of cognitive outcome using MMSE or MoCA persisted after adjustments of age, sex, admission Glasgow Coma Scale, and surgery. In patients who completed the comprehensive neuropsychological assessments, cognitive impairment in at least one of the neuropsychological tests was noted in 73% of them. CONCLUSIONS: Cognitive dysfunction had a significant impact on functional outcome, and treatment strategy should be developed to minimize them.