Patricia M. Arenth

Applications of Functional Near-Infrared Spectroscopy (fNIRS) to Neurorehabilitation of Cognitive Disabilities

Functional Near-Infrared Spectroscopy (fNIRS) is a neuroimaging technique that utilizes light in the near-infrared spectrum (between 700 and 1000 nm) to detect hemodynamic changes within the cortex when sensory, motor, or cognitive activation occurs. FNIRS principles have been used to study brain oxygenation for several decades, but have more recently been applied to study cognitive processes. This paper provides a description of basic fNIRS techniques, and provides a review of the rehabilitation-related literature. The authors discuss strengths and weaknesses of this technique, assert that fNIRS may be particularly beneficial to neurorehabilitation of cognitive disabilities, and suggest future applications.

Exploratory associations with tumor necrosis factor-α, disinhibition and suicidal endorsement after traumatic brain injury.

PURPOSE To examine the relationship of Tumor Necrosis Factor (TNF)-α to disinhibition and suicidal endorsement after traumatic brain injury (TBI). PARTICIPANTS Adults with moderate to severe TBI (acute serum levels: n=48, n=543 samples; acute CSF levels: n=37, n=389 samples; chronic serum levels: n=48, n=326 samples). MAIN MEASURES TNFα levels (CSF, Serum) from time of injury to 12 months post-injury; Frontal Systems Behavior Scale - Disinhibition Subscale at 6 and 12 months post-injury; Patient Health Questionnaire at 6 and 12 months post-injury. RESULTS Participants with TBI had significantly higher CSF and serum TNFα levels than healthy controls (p<0.05). Acute and chronic serum TNFα was significantly associated with disinhibition at 6 months post-injury (p=0.009, p=0.029 respectively), and 6 month disinhibition was associated with suicidal endorsement at both 6 and 12 months (p=0.045, p=0.033 respectively) and disinhibition at 12 months post-injury (p<0.001). CONCLUSION These preliminary data suggest a biological to behavioral pathway of suicidality after TBI, from TNFα to disinhibition to suicidal endorsement. Future investigation is warranted to validate these findings and clarify what biological mechanisms might underlie these relationships.

Persistent hypogonadism influences estradiol synthesis, cognition and outcome in males after severe TBI

Objective: Acute hypogonadotropic hypogonadism (AHH) occurs frequently after TBI, as does chronic hypogonadotropic hypogonadism. However, AHH and persistent hypogonadotropic hypogonadism (PHH) after TBI are not well studied. The objective of this study was to characterize longitudinal hormone profiles and the impact of AHH and PHH on outcome. Methods: In this prospective cohort study, men with severe TBI (n = 38) had serum gonadal and gonadotropic hormones measured during weeks 1–52 post-injury. AHH, PHH and/or early resolving hypogonadotropic hypogonadism (ERHH) were based on temporal hormone assessments. PHH and hormone profiles were then compared to multiple outcome measures 6–12 months post-TBI. Results: AHH affected 100% of the population, while 37% subsequently developed PHH. Acute testosterone (TEST) and estradiol/testosterone (E2/TEST) ratios were associated with PHH and outcome. Over time, post-acute TEST and E2 levels for the ERHH group approached normal range, while levels for the PHH group remained low. Post-acute gonadotrophin levels were within the normal range for both groups. PHH, along with lower post-acute TEST and E2 profiles, was associated with worse functional and cognitive outcomes at 6 and 12 months post-injury. Conclusions: These results support screening for post-acute secondary hypogonadism and further research to assess the mechanisms underlying PHH and associated functional and cognitive deficits.

Corpus callosum integrity and neuropsychological performance after traumatic brain injury: a diffusion tensor imaging study.

Objectives:(1) Detailed analysis of diffusion tensor imaging (DTI) parameters (fractional anisotropy and radial diffusivity) to evaluate white matter integrity in the corpus callosum (CC), and (2) examine correlations between DTI data and performance on multiple measures of cognitive functioning. Participants:Twelve individuals with a history of complicated mild, moderate, or severe traumatic brain injury (TBI) who were an average of 1.7 years postinjury and 12 control participants. Main Measures:Standardized and experimental neuropsychological tests; detailed analysis of DTI parameters. Results:The TBI group demonstrated DTI values suggesting decreased white matter integrity and correlations with severity of injury. Both groups showed correlations between DTI parameters and cognitive measures, with more significant correlations observed for the TBI group. White matter changes in the CC were evident chronically and were related to severity of injury. Conclusions:Diffusion tensor imaging parameters suggesting disruptions in white matter in the CC may be implicated in impaired performance, both in terms of cognitive tasks and reaction time, after TBI.

Unique Contribution of Fatigue to Disability in Community-Dwelling Adults With Traumatic Brain Injury

OBJECTIVE To examine the unique contribution of fatigue to self-reported disability in community-dwelling adults with traumatic brain injury (TBI). DESIGN A cross-sectional cohort design. SETTING Community dwellings. PARTICIPANTS Adults (N=50) with a history of mild to severe TBI were assessed. INTERVENTION Not applicable. MAIN OUTCOME MEASURES This study assessed the contribution of fatigue (Modified Fatigue Impact Scale) to disability (Mayo-Portland Adaptability Inventory), controlling for executive functions (Frontal Systems Behavior Scale), depression status (major depression in partial remission/current major depression/depressive symptoms or no history of depression), and initial injury severity (uncomplicated mild, complicated mild, moderate, or severe). RESULTS Fatigue was found to contribute uniquely to the variance in self-reported disability (β=.47, P<.001) after controlling for injury severity, executive functions, and depression status. The overall model was significant (F(4,45)=17.32, P<.001) and explained 61% of the variance in self-reported disability, with fatigue alone accounting for 12% of the variance in self-reported disability (F(1,45)=13.97, P<.001). CONCLUSIONS Fatigue contributes uniquely to disability status among community-dwelling adults with chronic TBI, independent of injury severity, executive functions, and depression. Addressing fatigue through targeted interventions may help to improve self-perceived disability in this population.

Early trajectory of psychiatric symptoms after traumatic brain injury: relationship to patient and injury characteristics.

Psychiatric disturbance is common and disabling after traumatic brain injury (TBI). Few studies have investigated the trajectory of psychiatric symptoms in the first 6 months postinjury, when monitoring and early treatment might prevent persistent difficulties. The aim of this study was to examine the trajectory of psychiatric symptoms 1-6 months post-TBI, the patient/injury characteristics associated with changes, and characteristics predictive of persisting symptoms. A secondary analysis was performed on data from a clinical trial with three data collection points. Across eight centers, 872 participants with complicated mild to severe TBI were administered the Brief Symptom Inventory (BSI) at 30, 90, and 180 days postinjury. Mixed-effects models were used to assess longitudinal changes in the BSI Global Severity Index (GSI). Multi-variate logistic regression was used to assess predictors of clinically significant GSI elevations persisting to 6 months post-TBI. In general, GSI scores improved over time. Women improved faster than men; race/ethnicity was also significantly associated with rate of change, with Hispanics showing the most and African Americans the least improvement. Clinically significant psychiatric symptoms (caseness) occurred in 42% of the sample at 6 months, and more than one type of symptom was common. Significant predictors of caseness included African American race, age from 30 to 60 years, longer post-traumatic amnesia (PTA) duration, pre-TBI unemployment, and pre-TBI risky alcohol use. Findings indicate that psychiatric symptoms are common in the first 6 months post-TBI and frequently extend beyond the depression and anxiety symptoms that may be most commonly screened. Patients with longer PTA and preinjury alcohol misuse may need more intensive monitoring for symptom persistence.

Preliminary associations between brain derived neurotrophic factor, memory impairment, functional cognition, and depressive symptoms following severe TBI

Background. Traumatic brain injury (TBI) often leads to mood and cognitive complications, affecting functional recovery. Understanding neurobiological alterations common in post-TBI depression (PTD) and cognition may identify novel biomarkers for TBI complications. Brain-derived neurotrophic factor (BDNF) is a likely target based on evidence of reduced BDNF signaling in experimental TBI and depression models and its role in learning and memory. Objective. To evaluate BDNF as a biomarker for PTD, cognitive impairment, and functional cognition in a prospective cohort with severe TBI. Methods. Participants with TBI (n = 113) were evaluated for PTD (Patient Health Questionnaire-9 [PHQ-9]), cognitive impairment (cognitive composite score), and functional cognition (Functional Independence Measure–Cognition, FIM-Cog). BDNF levels were measured in cerebrospinal fluid and serum at 0 to 6 days postinjury and in serum at 6 and 12 months postinjury. Results. Serum BDNF was reduced after TBI versus controls at all time points. Acute serum BDNF positively correlated with memory composites (6 months: r = 0.43, P = .019, n = 30; 12 months: r = 0.53, P = .005, n = 26) and FIM-Memory scores (6 months: r = 0.35, P = .019, n = 45; 12 months: r = 0.38, P = .018, n = 38). Acute serum BDNF negatively correlated with 12-month PHQ-9 scores (r = −0.38; P = .044; n = 29). At 12 months, chronic serum BDNF tended to be lower in participants with PTD (P = .07) and correlated with PHQ-9 scores (r = −0.41; P = .019; n = 32). Conclusions. Acute BDNF associations with memory recovery may implicate hippocampal damage/degeneration. Comparatively, BDNF associations with PTD status were not as strong as associations with PTD severity. Further investigation may delineate longitudinal BDNF patterns, and BDNF responsive treatments, reflecting mood and cognitive recovery following TBI.

Trajectories of Life Satisfaction After Traumatic Brain Injury: Influence of Life Roles, Age, Cognitive Disability, and Depressive Symptoms

OBJECTIVES (a) Identify life satisfaction trajectories after moderate to severe traumatic brain injury (TBI); (b) establish a predictive model for these trajectories across the first 5 years postinjury; and (c) describe differences in these life satisfaction trajectory groups, focusing on age, depressive symptoms, disability, and participation in specific life roles. RESEARCH METHOD Analysis of the longitudinal TBI Model Systems National Database was performed on data collected prospectively at 1-, 2-, and 5-years post-TBI. Participants (n = 3,012) had a moderate to severe TBI and were 16 years old and older. RESULTS Four life satisfaction trajectories were identified across the first 5 years postinjury, including: stable satisfaction, initial satisfaction declining, initial dissatisfaction improving, and stable dissatisfaction. Age, depressive symptoms, cognitive disability, and life role participation as a worker, leisure participant, and/ or religious participant at 1-year postinjury significantly predicted trajectory group membership. Life role participation and depressive symptoms were strong predictors of life satisfaction trajectories across the first 5 years post-TBI. CONCLUSIONS The previously documented loss of life roles and prevalence of depression after a moderate to severe TBI make this a vulnerable population for whom low or declining life satisfaction is a particularly high risk. Examining individual life role participation may help to identify relevant foci for community-based rehabilitation interventions or supports.

Pilot feasibility of an mHealth system for conducting ecological momentary assessment of mood-related symptoms following traumatic brain injury.

Abstract Objective: This study assessed pilot feasibility and validity of a mobile health (mHealth) system for tracking mood-related symptoms after traumatic brain injury (TBI). Design: A prospective, repeated measures design was used to assess compliance with daily ecological momentary assessments (EMA) conducted via a smartphone application over an 8-week period. Methods: An mHealth system was developed specifically for individuals with TBI and utilized previously validated tools for depressive and anxiety symptoms (Patient Health Questionnaire-9, Generalized Anxiety Disorder-7). Feasibility was assessed in 20 community-dwelling adults with TBI via an assessment of compliance, satisfaction and usability of the smartphone applications. The authors also developed and implemented a clinical patient safety management mechanism for those endorsing suicidality. Results: Participants correctly completed 73.4% of all scheduled assessments, demonstrating good compliance. Daily assessments took <2 minutes to complete. Participants reported high satisfaction with smartphone applications (6.3 of 7) and found them easy to use (6.2 of 7). Comparison of assessments obtained via telephone-based interview and EMA demonstrated high correlations (r = 0.81–0.97), supporting the validity of conducting these assessments via smartphone application in this population. Conclusions: EMA conducted via smartphone demonstrates initial feasibility among adults with TBI and presents numerous opportunities for long-term monitoring of mood-related symptoms in real-world settings.

CDP-Choline as a Biological Supplement During Neurorecovery: A Focused Review

Cytidine 5′‐diphosphocholine (CDP‐choline or citicoline) is a highly bioavailable compound with potential benefits for aiding neural repair and increasing acetylcholine levels in the central and peripheral nervous system. As a result, many researchers have investigated the use of CDP‐choline for various types of neurological insult or conditions, including stroke, traumatic brain injury, and Alzheimer disease. Despite the fact that the safety of the compound has been verified across multiple international studies, evidence for efficacy remains less clear. This may be attributable, at least in part, to several issues, including a lack of randomized clinical trials, a lack of availability of the compound in the United States, and statistical power issues in reported trials. In addition, the fact that CDP‐choline has multiple potential points of therapeutic impact makes it an exciting treatment option in theory but also complicates the analysis of efficacy in the sense that multiple mechanisms and time points must be evaluated. Although some clinical conditions do not appear to benefit from CDP‐choline treatment, the majority of findings to date have suggested at least minor benefits of treatment. In this review we will examine the evidence in the published literature pertaining to use of CDP‐choline in rehabilitation populations and briefly consider the work yet to be done.