Functional outcome is tied to dynamic brain states after mild to moderate traumatic brain injury.
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ABSTRACT:
SUBMITTER: van der Horn HJ
PROVIDER: S-EPMC7268079 | biostudies-literature | 2020 Feb
REPOSITORIES: biostudies-literature
Publications
Functional outcome is tied to dynamic brain states after mild to moderate traumatic brain injury.
van der Horn Harm J HJ Vergara Victor M VM Espinoza Flor A FA Calhoun Vince D VD Mayer Andrew R AR van der Naalt Joukje J
Human brain mapping 20191021 3
The current study set out to investigate the dynamic functional connectome in relation to long-term recovery after mild to moderate traumatic brain injury (TBI). Longitudinal resting-state functional MRI data were collected (at 1 and 3 months postinjury) from a prospectively enrolled cohort consisting of 68 patients with TBI (92% mild TBI) and 20 healthy subjects. Patients underwent a neuropsychological assessment at 3 months postinjury. Outcome was measured using the Glasgow Outcome Scale Exten ...[more]
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Project description:ObjectivesResearch suggests that the majority of mild traumatic brain injury (mTBI) patients exhibit both cognitive and emotional dysfunction within the first weeks of injury, followed by symptom resolution 3-6 months postinjury. The neuronal correlates of said dysfunction are difficult to detect with standard clinical neuroimaging, complicating differential diagnosis and early identification of patients who may not recover. This study examined whether resting state functional magnetic resonance imaging (fMRI) provides objective markers of injury and predicts cognitive, emotional, and somatic complaints in mTBI patients semiacutely (<3 weeks postinjury) and in late recovery (3-5 month) phases.MethodsTwenty-seven semiacute mTBI patients and 26 gender, age, and education-matched controls were studied. Fifteen of 27 patients returned for a follow-up visit 3-5 months postinjury. The main dependent variables were spontaneous fluctuations (temporal correlation) in the default-mode (DMN) and fronto-parietal task-related networks as measured by fMRI.ResultsSignificant differences in self-reported cognitive, emotional, and somatic complaints were observed (all P < 0.05), despite normal clinical (T1 and T2) imaging and neuropsychological testing results. Mild TBI patients demonstrated decreased functional connectivity within the DMN and hyper-connectivity between the DMN and lateral prefrontal cortex. Measures of functional connectivity exhibited high levels of sensitivity and specificity for patient classification and predicted cognitive complaints in the semi-acute injury stage. However, no changes in functional connectivity were observed across a 4-month recovery period.ConclusionsAbnormal connectivity between the DMN and frontal cortex may provide objective biomarkers of mTBI and underlie cognitive impairment.
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Project description:The objective of this study was to estimate the independent association of sex with outcome after mild traumatic brain injury (mTBI). We performed an analysis of a subset of an established cohort involving 1425 mTBI patients presenting to an academic emergency department (ED). The associations between sex and three outcomes determined 3 months after the initial ED visit were examined: post-concussive symptom (PCS) score (0, 1-5, 6-16, and >16), the number of days to return of normal activities (0, 1-7, and >7), and the number of days of work missed (0, 1-7,and >7). Logistic regression analyses were used to determine the relationship between sex and each outcome after controlling for 12 relevant subject-level variables. Of the 1425 subjects, 643 (45.1%) were female and 782 (54.9%) were male. Three months after mTBI, males had significantly lower odds of being in a higher PCS score category (odds ratio [OR] 0.62, 95% confidence interval [CI]: 0.50, 0.78); this association appeared to be more prominent during child-bearing years for females. Males and females did not significantly differ with respect to the odds of poorer outcome as defined by the number of days to return of normal activities or the number of days of work missed. Female sex is associated with significantly higher odds of poor outcome after mTBI, as measured by PCS score, after control for appropriate confounders. The observed pattern of peak disability for females during the child-bearing years suggests disruption of endogenous estrogen or progesterone production. Attempts to better understand how mTBI affects production of these hormones acutely after injury and during the recovery period may shed light on the mechanism behind poorer outcome among females and putative therapeutic interventions.
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Project description:(1) Background: White matter changes among individuals with mild-to-moderate traumatic brain injury (TBI) may be sensitive imaging markers reflecting functional impairment, particularly in the context of post-concussion syndrome. The objective of this study was to examine the altered white matter integrity in mild-to-moderate TBI patients compared with age-matched normal controls. (2) Methods: Diffusion tensor imaging data from 15 individuals with TBI and 15 control subjects were retrospectively obtained. We investigated and compared white matter integrity in both groups, with regard to fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) and examined the relationship with cognitive dysfunction and impaired balance in patients. (3) Results: In comparison with controls, the TBI patients had significantly decreased FA as well as increased RD, in the right corticospinal tract. Decreased RD was observed in the left cerebellar area near the middle cerebellar peduncle. Decreased AD was observed in the left inferior cerebellar peduncle, showing positive correlation with poor balance control. We observed decreased FA and increased AD in the left superior longitudinal fasciculus showing positive and negative correlation, respectively, with cognitive function in the TBI group. (4) Conclusions: Altered white matter integrity in mild-to-moderate TBI cases may be indicative of cognitive dysfunction and impaired balance.
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Project description:Mild traumatic brain injury (mTBI) results in variable clinical trajectories and outcomes. The source of variability remains unclear, but may involve genetic variations, such as single nucleotide polymorphisms (SNPs). A SNP in catechol-o-methyltransferase (COMT) is suggested to influence development of post-traumatic stress disorder (PTSD), but its role in TBI remains unclear. Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether the COMT Val158Met polymorphism is associated with PTSD and global functional outcome as measured by the PTSD Checklist - Civilian Version and Glasgow Outcome Scale Extended (GOSE), respectively. Results in 93 predominately Caucasian subjects with mTBI show that the COMT Met158 allele is associated with lower incidence of PTSD (univariate odds ratio (OR) of 0.25, 95% CI [0.09-0.69]) and higher GOSE scores (univariate OR 2.87, 95% CI [1.20-6.86]) 6-months following injury. The COMT Val158Met genotype and PTSD association persists after controlling for race (multivariable OR of 0.29, 95% CI [0.10-0.83]) and pre-existing psychiatric disorders/substance abuse (multivariable OR of 0.32, 95% CI [0.11-0.97]). PTSD emerged as a strong predictor of poorer outcome on GOSE (multivariable OR 0.09, 95% CI [0.03-0.26]), which persists after controlling for age, GCS, and race. When accounting for PTSD in multivariable analysis, the association of COMT genotype and GOSE did not remain significant (multivariable OR 1.73, 95% CI [0.69-4.35]). Whether COMT genotype indirectly influences global functional outcome through PTSD remains to be determined and larger studies in more diverse populations are needed to confirm these findings.
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Project description:ObjectiveTo develop a measure of global functioning after moderate-severe TBI with similar measurement precision but a longer measurement range than the FIM.DesignPhase 1: retrospective analysis of 5 data sets containing FIM, Disability Rating Scale, and other assessment items to identify candidate items for extending the measurement range of the FIM; Phase 2: prospective administration of 49 candidate items from phase 1, with Rasch analysis to identify a unidimensional scale with an extended range.SettingSix TBI Model System rehabilitation hospitals.ParticipantsIndividuals (N=184) with moderate-severe injury recruited during inpatient rehabilitation or at 1-year telephone follow-up.InterventionsParticipants were administered the 49 assessment items in person or via telephone.Main outcome measuresItem response theory parameters: item monotonicity, infit/outfit statistics, and Factor 1 variance.ResultsAfter collapsing misordered rating categories and removing misfitting items, we derived the Brain Injury Functional Outcome Measure (BI-FOM), a 31-item assessment instrument with high reliability, greatly extended measurement range, and improved unidimensionality compared with the FIM.ConclusionsThe BI-FOM improves global measurement of function after moderate-severe brain injury. Its high precision, relative lack of floor and ceiling effects, and feasibility for telephone follow-up, if replicated in an independent sample, are substantial advantages.
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