Posts Tagged mTBI

[REVIEW ARTICLE] Blood Biomarkers for Traumatic Brain Injury: A Quantitative Assessment of Diagnostic and Prognostic Accuracy – Full Text

Blood biomarkers have been explored for their potential to provide objective measures in the assessment of traumatic brain injury (TBI). However, it is not clear which biomarkers are best for diagnosis and prognosis in different severities of TBI. Here, we compare existing studies on the discriminative abilities of serum biomarkers for four commonly studied clinical situations: detecting concussion, predicting intracranial damage after mild TBI (mTBI), predicting delayed recovery after mTBI, and predicting adverse outcome after severe TBI (sTBI). We conducted a literature search of publications on biomarkers in TBI published up until July 2018. Operating characteristics were pooled for each biomarker for comparison. For detecting concussion, 4 biomarker panels and creatine kinase B type had excellent discriminative ability. For detecting intracranial injury and the need for a head CT scan after mTBI, 2 biomarker panels, and hyperphosphorylated tau had excellent operating characteristics. For predicting delayed recovery after mTBI, top candidates included calpain-derived αII-spectrin N-terminal fragment, tau A, neurofilament light, and ghrelin. For predicting adverse outcome following sTBI, no biomarker had excellent performance, but several had good performance, including markers of coagulation and inflammation, structural proteins in the brain, and proteins involved in homeostasis. The highest-performing biomarkers in each of these categories may provide insight into the pathophysiologies underlying mild and severe TBI. With further study, these biomarkers have the potential to be used alongside clinical and radiological data to improve TBI diagnostics, prognostics, and evidence-based medical management.

Introduction

Traumatic brain injury (TBI) is a common cause of disability and mortality in the US (1) and worldwide (2). Pathological responses to TBI in the CNS include structural and metabolic changes, as well as excitotoxicity, neuroinflammation, and cell death (34). Fluid biomarkers that may track these injury and inflammatory processes have been explored for their potential to provide objective measures in TBI assessment. However, at present there are limited clinical guidelines available regarding the use of biomarkers in both the diagnosis of TBI and outcome prediction following TBI. To inform future guideline formulation, it is critical to distinguish between different clinical situations for biomarker use in TBI, such as detection of concussion, prediction of positive and negative head computed tomography (CT) findings, and prediction of outcome for different TBI severities. This allows for comparisons to determine which biomarkers may be used most appropriately to characterize different aspects of TBI.

The identification of TBI severity has become a contentious issue. Currently, inclusion in TBI clinical trials is primarily based on the Glasgow Coma Scale (GCS), which stratifies patients into categories of mild, moderate, and severe TBI. The GCS assesses consciousness and provides prognostic information, but it does not inform the underlying pathologies that may be targeted for therapy (56). Furthermore, brain damage and persistent neurological symptoms can occur across the spectrum of TBI severity, limiting the use of GCS-determined injury severity to inform clinical management. Biomarkers in TBI have the potential to provide objective and quantitative information regarding the pathophysiologic mechanisms underlying observed neurological deficits. Such information may be more appropriate for guiding management than initial assessments of severity alone. Since the existing literature primarily focuses on applications of biomarkers in either suspected concussion, mild TBI (mTBI), or severe TBI (sTBI), we will discuss biomarker usage in these contexts.

Concussion is a clinical syndrome involving alteration in mental function induced by head rotational acceleration. This may be due to direct impact or unrestrained rapid head movements, such as in automotive crashes. Although there are over 30 official definitions of concussion, none include the underlying pathology. Missing from the literature have been objective measures to not only identify the underlying pathology associated with the given clinical symptoms, but also to indicate prognosis in long-term survival. Indeed, current practices in forming an opinion of concussion involve symptom reports, neurocognitive testing, and balance testing, all of which have elements of subjectivity and questionable reliability (7). While such information generally reflects functional status, it does not identify any underlying processes that may have prognostic or therapeutic consequences. Furthermore, because patients with concussion typically present with negative head CT findings, there is a potential role for blood-based biomarkers to provide objective information regarding the presence of concussion, based on an underlying pathology. This information could inform management decisions regarding resumption of activities for both athletes and non-athletes alike.

Blood-based biomarkers have utility far beyond a simple detection of concussion by elucidating specific aspects of the injury that could drive individual patient management. For example, biomarkers may aid in determining whether a mTBI patient presenting to the emergency department requires a CT scan to identify intracranial pathology. The clinical outcome for a missed epidural hematoma in which the patient is either discharged or admitted for routine observation is catastrophic; 25% are left severely impaired or dead (8). The Canadian CT Head Rule (9) and related clinical decision instruments achieve high sensitivities in predicting the need for CT scans in mild TBI cases. However, they do this at specificities of only 30–50% (10). Adding a blood biomarker to clinical evaluation may be useful to improve specificity without sacrificing sensitivity, as recently suggested (11). In addition, given concern about radiation exposure from head CT scans in concussion cases, particularly in pediatric populations, identification of patients who would be best assessed with neuroimaging is crucial. Thus, the use of both sensitive and specific biomarkers may serve as cost-effective tools to aid in acute assessment, especially in the absence of risk factors for intracranial injury (12). S-100B, an astroglial protein, has been the most extensively studied biomarker for TBI thus far and has been incorporated into some clinical guidelines for CT scans (1314). However, S-100B is not CNS-specific (1516) and has shown inconsistent predictive capacity in the outcome of mild TBI (1718). Given that several other promising biomarkers have also been investigated in this context, it is important to evaluate and compare the discriminative abilities of S-100B with other candidate blood-based biomarkers for future use.

Blood biomarkers also have the potential to help predict unfavorable outcomes across the spectrum of TBI severity. Outcome predication is difficult; in mTBI, existing prognostic models performed poorly in an external validation study (19). Identifying biomarkers that best predict delayed recovery or persistent neurological symptoms following mTBI would help with the direction of resources toward patients who may benefit most from additional rehabilitation or prolonged observation. In sTBI, poorer outcome has often been associated with a low GCS score (20). However, factors such as intoxication or endotracheal intubation may make it difficult to assess GCS reliably in the acute setting (2122). The addition of laboratory parameters to head CT and admission characteristics have improved prognostic models (23). Thus, prognostic biomarkers in sTBI could help determine whether patients are likely to benefit from intensive treatment. Several candidate biomarkers that correlate with various pathologies of mild and severe TBI have been studied (24), but their relative prognostic abilities remain unclear.

Existing reviews on biomarkers in TBI have provided valuable insight into the pathologic correlates of biomarkers, as well as how biomarkers may be used for diagnosis and prognosis (2531). However, there has been no previous quantitative comparison of the literature regarding biomarkers’ discriminative abilities in specific clinical situations. Here, we compare existing studies on the discriminative abilities of serum biomarkers for four commonly studied clinical situations: detecting concussion, predicting intracranial damage after mTBI, predicting delayed recovery after mTBI, and predicting adverse outcome after sTBI.[…]

 

Continue —-> Frontiers | Blood Biomarkers for Traumatic Brain Injury: A Quantitative Assessment of Diagnostic and Prognostic Accuracy | Neurology

Figure 2. Anatomical locations of potential TBI biomarkers. The biomarkers included in this schematic all rated as “good” (AUC=0.800.89) or better for any of the four clinical situations studied (detecting concussion, predicting intracranial damage after concussion, predicting delayed recovery after concussion, and predicting adverse outcome after severe TBI). Biomarkers with a pooled AUC <0.8 are not shown. 1Also found in adipose tissue; 2synthesized in cells of stomach and pancreas; may regulate HPA axis; 3found mostly in pons; 4also found extracellularly; 5lectin pathway of the complement system; 6also found in endothelial cells. BBB, blood brain barrier. ECM, Extracellular matrix. Image licensed under Creative Commons Attribution-ShareAlike 4.0 International license. https://creativecommons.org/licenses/by-sa/4.0/deed.en. See Supplementary Material for image credits and licensing.

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[ARTICLE] Effort and Fatigue-Related Functional Connectivity in Mild Traumatic Brain Injury – Full Text

Mental fatigue in healthy individuals is typically observed under conditions of high cognitive demand, particularly when effort is required to perform a task for a long period of time—thus the concepts of fatigue and effort are closely related. In brain injured individuals, mental fatigue can be a persistent and debilitating symptom. Presence of fatigue after brain injury is prognostic for return to work/school and engagement in activities of daily life. As such, it should be a high priority for treatment in this population, but because there is little understanding of its behavioral and neural underpinnings, the target for such treatment is unknown. Here, the neural underpinnings of fatigue and effort are investigated in active duty military service members with mild traumatic brain injury (mTBI) and demographically-matched orthopedic controls. Participants performed a Constant Effort task for which they were to hold a pre-defined effort level constant for long durations during fMRI scanning. The task allowed for investigation of the neural systems underlying fatigue and their relationship with sense of effort. While brain activation associated with effort and fatigue did not differentiate the mTBI and controls, functional connectivity amongst active brain regions did. The mTBI group demonstrated immediate hyper-connectivity that increased with effort level but diminished quickly when there was a need to maintain effort. Controls, in contrast, demonstrated a similar pattern of hyper-connectivity, but only when maintaining effort over time. Connectivity, particularly between the left anterior insula, rostral anterior cingulate cortex, and right-sided inferior frontal regions, correlated with effort-level and state fatigue in mTBI participants. These connections also correlated with effort level in the Control group, but only the connection between the left insula and superior medial frontal gyrus correlated with fatigue, suggesting a differing pattern of connectivity. These findings align, in part, with the dopamine imbalance, and neural efficiency hypotheses that pose key roles for medial frontal connections with insular or striatal regions in motivating or optimizing performance. Sense of effort and fatigue are closely related. As people fatigue, sense of effort increases systematically. The data propose a complex link between sense of effort, fatigue, and mTBI that is centered in what may be an inefficient neural system due to brain trauma that warrants further investigation.

Introduction

A signature injury of service members deployed during the conflicts in Iraq and Afghanistan is traumatic brain injury (TBI). Of the approximately 360,000 service members who suffer from TBI, 70% are classified as mild injuries (mTBI; DVBIC Quarterly Reports). At least 19% of the service members with mTBI have persistent symptoms that contribute to difficulty engaging in social and work activities. The consequences of persistent fatigue in mTBI pose a real challenge to rehabilitation (1). High levels of mental fatigue commonly persist and relate to failure to return to work and loss of productivity (23). In fact, presence of fatigue is the strongest predictive factor of poor outcomes following TBI (1). Despite the prevalence of fatigue in TBI, our understanding of its behavioral and neural underpinnings is lacking.

Mental fatigue is a complex process that is operationally defined by time on task and increased mental effort. When performance suffers (reaction time, accuracy, etc.) over time, presumably from fatigue, there tends to be fairly diffusely increased brain activity (4). Simultaneously, there may also be decreased motivation under high effort (5). According to Kahneman’s “resource capacity theory,” the amount of effort needed to perform a task is related to the complexity of the task and an individual’s limited general capacity to perform mental work [i.e., resource capacity, (67)]. When a task is difficult, the demand for resources is high, and performance suffers when resources near depletion. When a person recognizes that performance is suffering, tasks are perceived as more difficult, and require greater effort, which Kahneman equates with the experience of mental fatigue.

Brain imaging in mTBI indicates an increase in brain activity with increased time on task regardless of the type or demand requirements of the task (8). In contrast, healthy individuals have decreased activation over time without a serious decrement in performance, and without reporting significant fatigue. This brain response in TBI may suggest a perception of higher levels of effort when the task is long, or that individuals with TBI inefficiently regulate cognitive control and exert more mental effort to maintain a high-level of performance, resulting in fatigue.

While there is a plethora of literature reporting that task demand causes degradation of performance in mTBI, few have investigated whether task demand results in fatigue more so than in healthy controls, or how this fatigue manifests in behavior or in neural function. The few available studies have small sample sizes [e.g., (9)] limiting their generalizability. The brain networks implicated in effort and fatigue include frontostriatal circuitry, or the ventromedial prefrontal cortex more specifically. Damage to these brain regions is thought to diminish resource capacity and impair allocation of resources, resulting in an increased perception of expended effort (1012). Additionally, fatigue related to lack of motivation to engage and maintain performance on a task, or to predict and manage change in performance based on feedback about performance, is associated with the integrity of the ventromedial prefrontal cortical. That is, individuals with larger lesions of this brain region report more fatigue and apathy (1314). The frontostriatal network is involved in coding the incentive value for an expected outcome (15), and is mediated by dopaminergic frontostriatal networks (131619). Breakdowns in ventromedial prefrontal cortex-related network connectivity may disrupt the ability to appropriately detect, monitor, and self-correct errors or to adequately motivate behavior (2021). For example, the anterior cingulate cortex is associated with monitoring and detecting errors, the pre-supplementary motor area with engaging in task, and the connectivity amongst these two regions is related to fatigue (22).

One gap in the existing literature on fatigue is that paradigms infer “probable” fatigue [exception is Wylie et al. (22)], rather than directly measuring it. In the present study, we investigate brain activity and network connectivity in mTBI participants while they perform a task explicitly designed to study the relationship between task-related effort and fatigue. We assess fatigue with a questionnaire about fatigue over the week prior to scanning (trait) as well as with task manipulation during brain imaging [state, Constant Effort Task [CE]]. For Constant Effort, subjects are asked to squeeze a bulb to a prescribed effort level and hold it constant for a discrete period of time. The task is considered a general index of central fatigue as it is not specific to motor system engagement (2324). Varying effort levels result in predictable changes in the ability to maintain pressure on the bulb such that the time it takes to fatigue is slower at low effort levels than at higher effort levels. Performance on the CE task during functional fMRI allowed for identification of the neural systems underlying effort and fatigue as well as the differences in these systems in mTBI relative to control. We hypothesize that fatigue in mTBI arises when there is an altered perception of the amount of effort needed to perform the task, either because there is a failure to:

a) update the amount of effort given to the task based on internal feedback about performance, which is assessed by contrasting performance across effort levels,

b) sustain a given effort level, which is assessed via time on task, or

c) both.

Because estimating and maintaining effort are likely a result of a complex network of interacting brain regions, we examined not only brain activation during task performance, but also functional connectivity (FC) amongst the regions active during the task. We predict that mTBI participants will demonstrate increased pre-frontal and anterior cingulate cortex activation, as well as increased connectivity of these regions to ventral-striatal regions relative to Control participants.[…]

 

Continue —> Frontiers | Effort and Fatigue-Related Functional Connectivity in Mild Traumatic Brain Injury | Neurology

Figure 1. Effort and Fatigue in the Constant Effort task demonstrated differing regional effects with effort associated with caudal, medial prefrontal cortex (red) while fatigue was associated with rostral prefrontal cortex as well as postcentral and posterior cingulate cortex (blue). Controls demonstrated significantly higher activity than mTBI in a small area of the right medial prefrontal cortex (green) while mTBI had more activity in the posterior occipital cortex, but there were no other significant group effects. When these regions were used in computing functional connectivity, it was only the connectivity amongst the regions of the effort effect (red) that demonstrated group differences in connection strength. For example, the connection between the left insula (A) and the right inferior frontal gyrus (B, pars orbitalis) was significantly stronger in the TBI group for time on task at 75% effort.

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[ARTICLE] Clinical Findings in a Multicenter MRI Study of Mild TBI

Abstract

Background: Uncertainty continues to surround mild traumatic brain injury (mTBI) diagnosis, symptoms, prognosis, and outcome due in part to a lack of objective biomarkers of injury and recovery. As mTBI gains recognition as a serious public health epidemic, there is need to identify risk factors, diagnostic tools, and imaging biomarkers to help guide diagnosis and management.

Methods: One hundred and eleven patients (15–50 years old) were enrolled acutely after mTBI and followed with up to four standardized serial assessments over 3 months. Each encounter included a clinical exam, neuropsychological assessment, and magnetic resonance imaging (MRI). Chi-square and linear mixed models were used to assess changes over time and determine potential biomarkers of mTBI severity and outcome.

Results: The symptoms most frequently endorsed after mTBI were headache (91%), not feeling right (89%), fatigue (86%), and feeling slowed down (84%). Of the 104 mTBI patients with a processed MRI scan, 28 (27%) subjects had white matter changes which were deemed unrelated to age, and 26 of these findings were deemed unrelated to acute trauma. Of the neuropsychological assessments tested, 5- and 6-Digit Backward Recall, the modified Balance Error Scoring System (BESS), and Immediate 5-Word Recall significantly improved longitudinally in mTBI subjects and differentiated between mTBI subjects and controls. Female sex was found to increase symptom severity scores (SSS) at every time point. Age ≥ 25 years was correlated with increased SSS. Subjects aged ≥ 25 also did not improve longitudinally on 5-Digit Backward Recall, Immediate 5-Word Recall, or Single-Leg Stance of the BESS, whereas subjects < 25 years improved significantly. Patients who reported personal history of depression, anxiety, or other psychiatric disorder had higher SSS at each time point.

Conclusions: The results of this study show that 5- and 6-Digit Backward Recall, the modified BESS, and Immediate 5-Word Recall should be considered useful in demonstrating cognitive and vestibular improvement during the mTBI recovery process. Clinicians should take female sex, older age, and history of psychiatric disorder into account when managing mTBI patients. Further study is necessary to determine the true prevalence of white matter changes in people with mTBI.

Introduction

Mild traumatic brain injury (mTBI) is defined as a traumatically induced physiological disruption of brain function (1). Although mTBI accounts for at least 75% of traumatic brain injuries and imposes an excessive societal burden (23), mTBI diagnosis continues to lack objective clinical and imaging biomarkers. As of now, the best marker for severity and recovery is a subjective assessment of acute symptom burden (4). Uncertainty continues to surround mTBI diagnosis, symptoms, prognosis, and outcome for physicians and patients as reliable biomarkers remain elusive. As injury rates increase and mTBI becomes a serious public health epidemic (5), there is an increasing role for identification of potential imaging biomarkers, specific neuropsychological assessments, and validated risk factors to help guide prognoses and return to play decisions.

Given the current subjective nature of symptom burden assessment, there is a role for neuropsychological assessments in evaluating the cognitive impairment of patients after injury. The sport concussion assessment tool (SCAT) has been demonstrated as an effective tool to differentiate between mTBI subjects and controls in non-athlete populations and is widely used in mTBI studies (68). Tests of memory, balance, and cognition are incorporated into the SCAT (910), but research has not demonstrated their effectiveness as longitudinal assessments (11). Separately, 3-word recall is commonly employed in patients with mTBI to assess memory function (12). This test is usually normal and is probably inadequate for assessing these patients.

The risk factors for mTBI severity are debated in the literature. Demographic factors commonly explored include sex, age, previous concussions, learning disability, psychiatric history, and migraine/headache history (13). Although each of these preinjury characteristics has been studied in numerous protocols, a consensus has not been reached. Further research is needed to establish the risk factors for mTBI severity so that they may be incorporated into clinical care.

Moreover, routine imaging techniques are limited in their value of serving as biomarkers of severity or prognosis in the mTBI population, and the extent of incidental magnetic resonance imaging (MRI) findings in mTBI patients also remains unclear. Conventional structural MR imaging is felt to be limited in its yield of disease severity or prognosis. Further research is necessary to investigate the anatomical characteristics of the mTBI population that present to medical attention. Better characterization of the specific abnormalities in anatomic imaging in this population is necessary.

The aim of this study was to incorporate patient history, clinical exams, imaging, and multiple neurological assessments into a prospective longitudinal study of patients presenting with an acute mild traumatic brain injury to provide guidance for hypothesis generation and future study design of mTBI research. Traditional neuropsychological assessments were developed to further attempt to detect abnormalities in patients with mTBI. Although MR imaging is not routinely performed for acute mTBI, recent advances in MRI based techniques have allowed researchers to incorporate imaging into mTBI trials. This study specifically investigated the presence of white matter hyperintensities on structural imaging. This combination of assessments and time points provided a more comprehensive and detailed assessment of symptoms and outcomes of mTBI patients than found in previous studies. This allows for identification of previously elusive potential risk factors which may influence outcome measures for mTBI populations.[…]

 

Continue —>  Frontiers | Clinical Findings in a Multicenter MRI Study of Mild TBI | Neurology

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[Study] Transcranial Electrical Stimulation for mTBI (TES for mTBI)

Recruitment Status  : Recruiting

Study Description

Brief Summary:

Mild traumatic brain injury (mTBI) is a leading cause of sustained physical, cognitive, emotional, and behavioral deficits in OEF/OIF/OND Veterans and the general public. However, the underlying pathophysiology is not completely understood, and there are few effective treatments for post-concussive symptoms (PCS). In addition, there are substantial overlaps between PCS and post-traumatic stress disorder (PTSD) symptoms in mTBI. IASIS is among a class of passive neurofeedback treatments that combine low-intensity pulses for transcranial electrical stimulation (LIP-tES) with electroencephalography (EEG) monitoring. LIP-tES techniques have shown promising results in alleviating PCS individuals with TBI. However, the neural mechanisms underlying the effects of LIP-tES treatment in TBI are unknown, owing to the dearth of neuroimaging investigations of this therapeutic intervention. Conventional neuroimaging techniques such as MRI and CT have limited sensitivity in detecting physiological abnormalities caused by mTBI, or in assessing the efficacy of mTBI treatments. In acute and chronic phases, CT and MRI are typically negative even in mTBI patients with persistent PCS. In contrast, evidence is mounting in support of resting-state magnetoencephalography (rs-MEG) slow-wave source imaging (delta-band, 1-4 Hz) as a marker for neuronal abnormalities in mTBI. The primary goal of the present application is to use rs-MEG to identify the neural underpinnings of behavioral changes associated with IASIS treatment in Veterans with mTBI. Using a double-blind placebo controlled design, the investigators will study changes in abnormal MEG slow-waves before and after IASIS treatment (relative to a ‘sham’ treatment group) in Veterans with mTBI. In addition, the investigators will examine treatment-related changes in PCS, PTSD symptoms, neuropsychological test performances, and their association with changes in MEG slow-waves. The investigators for the first time will address a fundamental question about the mechanism of slow-waves in brain injury, namely whether slow-wave generation in wakefulness is merely a negative consequence of neuronal injury or if it is a signature of ongoing neuronal rearrangement and healing that occurs at the site of the injury. Specific Aim 1 will detect the loci of injury in Veterans with mTBI and assess the mechanisms underlying functional neuroimaging changes related to IASIS treatment using rs-MEG slow-wave source imaging. The investigators hypothesize that MEG slow-wave source imaging will show significantly higher sensitivity than conventional MRI in identifying the loci of injury on a single-subject basis. The investigators also hypothesize that in wakefulness, slow-wave generation is a signature of ongoing neural rearrangement / healing, rather than a negative consequence of neuronal injury. Furthermore, the investigators hypothesize IASIS will ultimately reduce abnormal MEG slow-wave generation in mTBI by the end of the treatment course, owing to the accomplishment of neural rearrangement / healing. Specific Aim 2 will examine treatment-related changes in PCS and PTSD symptoms in Veterans with mTBI. The investigators hypothesize that compared with the sham group, mTBI Veterans in the IASIS treatment group will show significantly greater decreases in PCS and PTSD symptoms between baseline and post-treatment assessments. Specific Aim 3 will study the relationship among IASIS treatment-related changes in rs-MEG slow-wave imaging, PCS, and neuropsychological measures in Veterans with mTBI. The investigators hypothesize that Reduced MEG slow-wave generation will correlate with reduced total PCS score, individual PCS scores (e.g., sleep disturbance, post-traumatic headache, photophobia, and memory problem symptoms), and improved neuropsychological exam scores between post-IASIS and baseline exams. The success of the proposed research will for the first time confirm that facilitation of slow-wave generation in wakefulness leads to significant therapeutic benefits in mTBI, including an ultimate reduction of abnormal slow-waves accompanied by an improvement in PCS and cognitive functioning.

MORE —>  Transcranial Electrical Stimulation for mTBI – No Study Results Posted – ClinicalTrials.gov

 

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[VIDEO] 5 Tips for Surviving the Holidays with an mTBI — How to manage your TBI & still enjoy the holidays – YouTube

Kim & Brie are back! This time they’re here to give you some tips on how to comfortably celebrate the holidays after a TBI. Post Concussion Syndrome can make holidays even more overwhelming than usual, but some forethought and planning can help. The TBI Rockstars guide you through some of their own holiday experiences post brain injury.

 

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[BLOG POST] Study: Transcranial e-stim beneficial in mild traumatic brain injury

Researchers from the University of California San Diego and from the Veterans Affairs San Diego Healthcare System have improved neural function in a group of people with mild traumatic brain injury using low-impulse electrical stimulation to the brain, according to a study published in Brain Injury.

Although little is understood about the pathology of mild TBI, the team of researchers noted that previous work has shown that passive neuro-feedback, low-intensity pulses applied to the brain through transcranial electrical stimulation, has promise as a potential treatment.

The team’s pilot study enrolled six people with mild TBI who were experiencing post-concussion symptoms. Researchers used a form of LIP-tES combined with concurrent electroencephalography monitoring and assessed the treatment’s effect using a non-invasive functional imaging technique, magnetoencephalography, before and after treatment.

“Our previous publications have shown that MEG detection of abnormal brain slow-waves is one of the most sensitive biomarkers for mild traumatic brain injury (concussions), with about 85 percent sensitivity in detecting concussions and, essentially, no false-positives in normal patients,” senior author Dr. Roland Lee said in prepared remarks. “This makes it an ideal technique to monitor the effects of concussion treatments such as LIP-tES.”

Researchers reported that the brains in all six patients had abnormal slow-waves at the time of initial scans. After treatment, MEG scans showed reduced abnormal slow-waves and the study participants reported a significant reduction in post-concussion scores.

“For the first time, we’ve been able to document with neuroimaging the effects of LIP-tES treatment on brain functioning in mild TBI,” first author Ming-Xiong Huang added. “It’s a small study, which certainly must be expanded, but it suggests new potential for effectively speeding the healing process in mild traumatic brain injuries.”

Source: Study: Transcranial e-stim beneficial in mild traumatic brain injury – MassDevice

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[ARTICLE] Fatigue and Cognitive Fatigability in Mild Traumatic Brain Injury are Correlated with Altered Neural Activity during Vigilance Test Performance – Full Text

Introduction: Fatigue is the most frequently reported persistent symptom following a mild traumatic brain injury (mTBI), but the explanations for the persisting fatigue symptoms in mTBI remain controversial. In this study, we investigated the change of cerebral blood flow during the performance of a psychomotor vigilance task (PVT) by using pseudo-continuous arterial spin labeling (PCASL) MRI technique to better understand the relationship between fatigability and brain activity in mTBI.

Material and methods: Ten patients (mean age: 37.5 ± 11.2 years) with persistent complaints of fatigue after mTBI and 10 healthy controls (mean age 36.9 ± 11.0 years) were studied. Both groups completed a 20-min long PVT inside a clinical MRI scanner during simultaneous measurements of reaction time and regional cerebral blood flow (rCBF) with PCASL technique. Cognitive fatigability and neural activity during PVT were analyzed by dividing the performance and rCBF data into quintiles in addition to the assessment of self-rated fatigue before and after the PVT.

Results: The patients showed significant fatigability during the PVT while the controls had a stable performance. The variability in performance was also significantly higher among the patients, indicating monitoring difficulty. A three-way ANOVA, modeling of the rCBF data demonstrated that there was a significant interaction effect between the subject group and performance time during PVT in a mainly frontal/thalamic network, indicating that the pattern of rCBF change for the mTBI patients differed significantly from that of healthy controls. In the mTBI patients, fatigability at the end of the PVT was related to increased rCBF in the right middle frontal gyrus, while self-rated fatigue was related to increased rCBF in left medial frontal and anterior cingulate gyri and decreases of rCBF in a frontal/thalamic network during this period.

Discussion: This study demonstrates that PCASL is a useful technique to investigate neural correlates of fatigability and fatigue in mTBI patients. Patients suffering from fatigue after mTBI used different brain networks compared to healthy controls during a vigilance task and in mTBI, there was a distinction between rCBF changes related to fatigability vs. perceived fatigue. Whether networks for fatigability and self-rated fatigue are different, needs to be investigated in future studies.

Introduction

Fatigue is a frequently reported symptom after mild traumatic brain injury (mTBI) (13) and a major reason why patients fail to return to work (4). The subjective experience of fatigue may be concomitant with physiological fatigue or with deteriorating performance, but may also be a sole complaint (56). Research on the relationship between underlying neural correlates to fatigue in mTBI, and possible performance decrements is complicated by the fact that fatigue is still not a well-defined concept. It is multidimensional in its nature, involving both physiological and psychological components (79) and, therefore, a single explanatory mechanism is unlikely (310).

Kluger and coworkers (11) suggested distinguishing the self-rated fatigue measures from objective measures of fatigue by labeling the later as fatigability. Such distinction might encourage among others more focused correlational studies; such as fatigue in relation to the neural activity. Measuring performance during sustained cognitive process provides a method to evaluate fatigue/fatigability objectively (1214). For example, sustained attention during vigilance performance is a demanding cognitive task and performance induced fatigability has been demonstrated as increased error rate and reaction time (15). Our group has also found fatigability in mTBI on a higher order attention demanding task (16).

More recently, we studied the behavioral correlates of changes in resting-state functional connectivity before and after performing a 20-min psychomotor vigilance task (PVT) for mTBI patients with persistent post-concussion fatigue (17). Taking advantage of a quantitative data-driven analysis approach developed by us, we were able to demonstrate that there was a significant linear correlation between the self-rated fatigue and functional connectivity in the thalamus and middle frontal cortex. Furthermore, we found that the 20 min PVT was sufficiently sensitive to invoke significant mental fatigue and specific functional connectivity changes in mTBI patients. These findings indicate that resting-state functional MRI (fMRI) measurements before and after a 20 min PVT may serve as a useful method for objective assessment of fatigue level in the neural attention system. However, these measurements neither provide any information about the dynamic change of the neural activities in the involved functional networks during the performance of PVT nor can they answer whether other neural systems mediate the observed functional connectivity change in the attention network.

Arterial spin labeling (ASL) MRI technique has recently been used to examine the cerebral blood flow (CBF) in patients with amnestic mild cognitive impairment and cognitively normal healthy controls both at rest and during the active performance of a memory task (18). As compared to rest, CBF measurement during the task performance showed increased group difference between patients and healthy controls indicating that CBF measures during a cognitive task may increase the discriminatory ability and the sensitivity to detect subtle functional changes in neurological diseases. In another ASL MRI study, Lim et al. (19) investigated the neural correlates of cognitive fatigue effects in a group of healthy volunteers during a 20-min PVT (19). They observed progressively slower reaction times and significantly increased mental fatigue ratings after the task and reported that such persistent cognitive fatigue effect was significantly correlated with regional cerebral blood flow (rCBF) decline in the right fronto-parietal attention network in addition to the basal ganglia and sensorimotor cortices. They also found that the rCBF at rest in the thalamus and right middle frontal gyrus before the PVT task was predictive of subjects’ subsequent performance decline. Based on these findings, they claimed that the rCBF at rest in the attention network might be a useful indicator of performance potential and a marker of the level of fatigue in neural attention system. However, it remains to be clarified how the relationship between the neural activity in mTBI patients and their fatigability is dynamically influenced by the performance of a difficult cognitive task.

Pseudo-Continuous Arterial Spin Labeling (PCASL) can provide quantitative rCBF measurements with whole-brain coverage and high signal-to-noise ratio. Furthermore, it is non-invasive and repetitive experiments can be carried out. It has been shown that fMRI experiments based on PCASL perfusion measurements may have higher sensitivity than experimental designs based on blood oxygenation level-dependent (BOLD) fMRI, particularly when studying slow neural activity changes within a subject (2022) and useful as a biomarker of brain function (18). To shed light on the questions discussed above, in this study we used PCASL MRI technique to measure the rCBF changes during a 20 min PVT in a group of mTBI patients with chronic fatigue and matched healthy control subjects. The aims of the present study are the following: (1) evaluate the PVT induced fatigability over time by dividing the performance data (error rate and reaction time) into quintiles to verify if the change of fatigability for mTBI patients follows the same pattern as that for healthy controls; (2) estimate the dynamic change of neural activity during PVT in terms of rCBF measurements in each quintile to reveal brain activities significantly associated with the change of fatigability. (3) Voxel-wise assessment of the rCBF values pre- and post-PVT to detect brain activity associated with changes in self-rated fatigue level. […]

Continue —> Frontiers | Fatigue and Cognitive Fatigability in Mild Traumatic Brain Injury are Correlated with Altered Neural Activity during Vigilance Test Performance | Neurology

Figure 4. Summary of the F-score results from the three-way ANOVA modeling of the regional cerebral blood flow data acquired during a 20-min psychomotor vigilance task (PVT) performance to illustrate the brain regions of statistically significant differences (family-wise error rate, p ≤ 0.05) in neural activity associated with the two fixed factors (the PVT performance time and subject group) and their interaction. (A) The effect of PVT performance time; (B) the interaction effect between the PVT performance time and subject groups. The color bar indicates the F-score of the three-way ANOVA results.

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[WEB SITE] Study: Magnetics Help Traumatic Brain Injury Headaches

Apr 15, 2015    |    Gale Scott

Drugs have not been shown effective in relieving the debilitating headaches that can follow mild traumatic brain injury (MTBI)

In a study presented at the American Society of Interventional Pain Physicians meeting in Orlando, FL April 11, Robert McLay, MD, PhD and colleagues at the University of California San Diego and the Veterans Administration San Diego Healthcare System in La Jolla, CA, looked at the effects of repetitive transcranial magnetic stimulation (rTMS).

The treatment involves using a basic electromagnetic coupling principle in which a rapid discharge of electric current is converted into dynamic magnetic flux allowing the induction of a localized current in the brain. The idea is to achieve neuromodulation. The treatment has been used for treating other types of headaches.

The researchers treated 6 men with MTBI headaches. To be included in the study, they had to have headaches lasting more than 48 hours. Measured on a pain scale, the average intensity of these headaches was 5.50 before treatment and 2.67 after receiving rTMS.

In addition, headache intensity was reduced by an average of 53.05%, and the average headache exacerbation frequency was reduced by 78.97% with 2 patients reporting no more severe headaches.

The authors concede that randomized trials are needed to confirm their results but say their findings are encouraging.

“MTBI headaches are often treatment-resistant, but in this case series patients were found to have improvements in severity, frequency and duration of their headaches after rTMS,” they wrote in the abstract.

The authors had no conflicts to disclose.

via Study: Magnetics Help Traumatic Brain Injury Headaches.

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[WEB SITE] Cognitive and Communication Disorders – Center for Neuro Skills

What Are the Cognitive and Communication Problems That Result From Traumatic Brain Injury?

Cognitive and communication problems that result from traumatic brain injury vary from person to person. These problems depend on many factors which include an individual’s personality, preinjury abilities, and the severity of the brain damage.

The effects of the brain damage are generally greatest immediately following the injury. However, some effects from traumatic brain injury may be misleading. The newly injured brain often suffers temporary damage from swelling and a form of “bruising” called contusions. These types of damage are usually not permanent and the functions of those areas of the brain return once the swelling or bruising goes away. Therefore, it is difficult to predict accurately the extent of long-term problems in the first weeks following traumatic brain injury.

Focal damage, however, may result in long-term, permanent difficulties. Improvements can occur as other areas of the brain learn to take over the function of the damaged areas. Children’s brains are much more capable of this flexibility than are the brains of adults. For this reason, children who suffer brain trauma might progress better than adults with similar damage.

more –> Traumatic Brain Injury Resource Guide – Cognitive and Communication Disorders.

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[WEB SITE] What is a Mild Traumatic Brain Injury (mTBI)?

…Brain injuries are classified mild, moderate, or severe. The leading causes are vehicle-related collisions, falls, sports injuries, and assaults. Of these brain injuries, 70-90% are considered “mild”. It is important to realize, however, that there is nothing “mild” about a traumatic brain injury.

A brain injury, of any classification, must be taken very seriously. The brain is complex; any injury that causes a disruption of its normal functioning is a traumatic injury.

Unfortunately, many people do not realize that a concussion is a mild traumatic brain injury (mTBI). Because of this, mTBIs are often not fully recognized or properly prioritized.

An mTBI affects each person differently. The extent and combination of effects will vary depending on the areas of the brain involved and the individual person.

Symptoms experienced by brain injury victims may include, but are not limited to:

  1. Physical: headaches, ringing in the ear, dizziness, insomnia, fatigue, trouble with senses
  2. Cognitive: problems with attention, concentration, memory, information processing, reasoning, planning
  3. Emotional: irritability, depression, anxiety, mood swings

These symptoms can last from a few hours to years. Concussions and mTBIs should not be dismissed, as their effects can be far-reaching. Instead, if you have been in an accident and are experiencing these symptoms, you should seek treatment for a brain injury.

Over the next few months, we will be releasing a series of videos dealing with this important topic.

Check back with us to learn about the following mTBI topics:

  • Why are Mild Traumatic Brain Injuries Often Missed?
  • Accessing Funding after Suffering an mTBI in a Motor Vehicle Accident
  • Finding the Right Team for Your Mild Traumatic Brain Injury
  • Coping with the Emotional and Psychological Impact of a Mild Traumatic Brain Injury

Roger R. Foisy is a knowledgeable Personal Injury Lawyer in Ontario with experience helping clients who have sustained brain injuries. If you have suffered a brain injury, do not hesitate to contact us today for immediate support and a free consultation.

via What is a Mild Traumatic Brain Injury (mTBI)? [Video].

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