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Although mild traumatic brain injury (mTBI), or concussion, is not typically associated with abnormalities on computed tomography (CT), it nevertheless causes persistent cognitive dysfunction for many patients. Consequently, new prognostic methods for mTBI are needed to identify at-risk cases, especially at an early and potentially treatable stage. Here, we quantified plasma levels of the neurodegeneration biomarker calpain-cleaved alphaII-spectrin N-terminal fragment (SNTF) from 38 participants with CT-negative mTBI, orthopedic injury (OI) and normal uninjured controls (age range 12-30 years), and compared them with findings from diffusion tensor magnetic resonance imaging (DTI) and long-term cognitive assessment. SNTF levels were at least twice the lower limit of detection in 7 of 17 mTBI cases and in 3 of 13 OI cases, but in none of the uninjured controls. An elevation in plasma SNTF corresponded with significant differences in fractional anisotropy and the apparent diffusion coefficient in the corpus callosum and uncinate fasciculus measured by DTI. Furthermore, increased plasma SNTF on the day of injury correlated significantly with cognitive impairment that persisted for at least 3 months, both across all study participants and also among the mTBI cases by themselves. The elevation in plasma SNTF in the subset of OI cases, accompanied by corresponding white matter and cognitive abnormalities, raises the possibility of identifying undiagnosed cases of mTBI. These data suggest that the blood level of SNTF on the day of a CT-negative mTBI may identify a subset of patients at risk of white matter damage and persistent disability. SNTF could have prognostic and diagnostic utilities in the assessment and treatment of mTBI.

The objective of this study was to understand how novel psychiatric disorders (NPD) in children with mild traumatic brain injury (MTBI) are related to pre-injury variables, injury-related variables, and concurrent neurocognitive outcome. A group of 79 children, ages 5 to 14 years, who had experienced MTBI, were studied from consecutive hospital admissions with semistructured psychiatric interviews soon after injury (baseline); 60 children were reassessed 12 months post-injury. Standardized instruments were used to assess injury severity; lesion characteristics; pre-injury variables, including psychiatric disorder, family psychiatric history, family functioning, socioeconomic status, psychosocial adversity, adaptive functioning, and post-injury neurocognitive and adaptive functioning. NPD occurred in 17 of 60 participants (28%) in the 6-12-month interval after injury, with disorders that were significantly associated with socioeconomic status, psychosocial adversity, estimated pre-injury academic functioning, and concurrent deficits in adaptive functioning, academic performance, processing speed, memory, and expressive language. NPD was not significantly associated with pre-injury adaptive functioning, injury severity, family psychiatric history, pre-injury psychiatric disorder, lesion location, gender, or age at injury. These findings suggest that the short-term psychiatric morbidity associated with MTBI in children occurs more commonly than previously reported and is related to both pre-injury social factors and concurrent neurocognitive functioning.

The ability to make accurate judgments about the mental states of others, sometimes referred to as theory of mind (ToM), is often impaired following traumatic brain injury (TBI), and this deficit may contribute to problems with interpersonal relationships. The present study used an animated social attribution task (SAT) with functional magnetic resonance imaging (fMRI) to examine structures mediating ToM in adolescents with moderate to severe TBI. The study design also included a comparison group of matched, typically developing (TD) adolescents. The TD group exhibited activation within a number of areas that are thought to be relevant to ToM, including the medial prefrontal and anterior cingulate cortex, fusiform gyrus, and posterior temporal and parietal areas. The TBI subjects had significant activation within many of these same areas, but their activation was generally more intense and excluded the medial prefrontal cortex. Exploratory regression analyses indicated a negative relation between ToM-related activation and measures of white matter integrity derived from diffusion tensor imaging, while there was also a positive relation between activation and lesion volume. These findings are consistent with alterations in the level and pattern of brain activation that may be due to the combined influence of diffuse axonal injury and focal lesions.

Structural damage to the prefrontal-cingulate network has been implicated in cognitive and neurobehavioral deficits associated with traumatic brain injury (TBI). Forty-six children who had sustained moderate-to-severe TBI and 43 children with extracranial injury were imaged using diffusion tensor imaging (DTI). Decreased fractional anisotropy (FA) and increased apparent diffusion coefficient (ADC) values were found in the cingulum bundles bilaterally in the TBI group. Cingulum ADC was related to frontal lesion volume, injury severity, and injury mechanism. Finally, cingulum DTI parameters were related to cognitive control measures. DTI detects TBI-related injury to the cingulum, which may facilitate advances in assessment and treatment.

Diffusion tensor imaging (DTI) was performed in 39 right-handed children to examine structural hemispheric differences and the impact of age, socioeconomic status and sex on these differences. Apparent diffusion coefficient (ADC) values were smaller in the left relative to the right temporal, prefrontal, anterior internal capsular, and the thalamic regions and fractional anisotropy (FA) values were larger in the left as compared to right internal capsule, thalamus, and cingulate. Significant region-by-sex interactions disclosed that the relation of DTI asymmetries to performance depended on sex including the relation of temporal lobes to reading comprehension and the relation of frontal lobes to solving applied mathematical problems.