Objective Documentation of Traumatic Brain Injury Subsequent to Mild Head Trauma

Lewine, Jeffrey D.; Davis, J. Terrance; Bigler, Erin D.; Thoma, Robert J.; Hill, Dina E.; Funke, Michael; Sloan, John H.; Hall, Sandra; Orrison, William W.

doi:10.1097/01.htr.0000271115.29954.27

Cited by 207 publications

(156 citation statements)

References 43 publications

(56 reference statements)

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“…Human studies by Lewine et al, and our laboratory showed that the brains of mTBI patients generate abnormal low-frequency magnetic fields that can be measured and localized by resting-state MEG (Huang et al, 2009(Huang et al, , 2012Lewine et al, 1999Lewine et al, , 2007. MEG was also found to be more sensitive than conventional MRI or EEG in detecting abnormalities in mTBI patients (Lewine et al, 1999(Lewine et al, , 2007.…”

Section: Clinicalmentioning

confidence: 72%

“…These experiments concluded that cortical de-afferentation was an important factor in abnormal delta-wave production, owing to WM lesions (i.e., axonal injury) and/or defects in the cholinergic pathway (Schaul, 1998). In the human brain, the projections of cholinergic pathways highly overlap with the WM fiber tracts (Selden et al, 1998), which make the cholinergic pathways similarly susceptible as the WM tracts to TBI.Human studies by Lewine et al, and our laboratory showed that the brains of mTBI patients generate abnormal low-frequency magnetic fields that can be measured and localized by resting-state MEG (Huang et al, 2009(Huang et al, , 2012Lewine et al, 1999Lewine et al, , 2007. MEG was also found to be more sensitive than conventional MRI or EEG in detecting abnormalities in mTBI patients (Lewine et al, 1999(Lewine et al, , 2007.…”

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confidence: 91%

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The role of biomarkers and MEG-based imaging markers in the diagnosis of post-traumatic stress disorder and blast-induced mild traumatic brain injury

Huang

Risling

Baker

2016

Psychoneuroendocrinology

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SummaryBackground: Pervasive use of improvised explosive devices (IEDs), rocket-propelled grenades, and land mines in the recent conflicts in Iraq and Afghanistan has brought traumatic brain injury (TBI) and its impact on health outcomes into public awareness. Blast injuries have been deemed signature wounds of these wars. War-related TBI is not new, having become prevalent during WWI and remaining medically relevant in WWII and beyond. Medicine's past attempts to accurately diagnose and disentangle the pathophysiology of war-related TBI parallels current lines of inquiry and highlights limitations in methodology and attribution of symptom etiology, be it organic, psychological, or behavioral. New approaches and biomarkers are needed. Preclinical: Serological biomarkers and biomarkers of injury obtained with imaging techniques represent cornerstones in the translation between experimental data and clinical observations. Experimental models for blast related TBI and PTSD can generate critical data on injury threshold, for example for white matter injury from acceleration. Carefully verified and validated models can be evaluated with gene expression arrays and proteomics to identify new candidates for serological biomarkers. Such models can also be analyzed with diffusion MRI and microscopy in order to identify criteria for detection of diffuse white matter injuries, such as DAI (diffuse axonal injury). The experimental models can also be analyzed with focus on injury outcome in brain stem regions, such as locus coeruleus or nucleus raphe magnus that can be involved in response to anxiety changes. * Corresponding author at: UCSD Radiology Imaging Laboratory, San Diego, CA 92121, USA. Tel.: +1 858 534 1254; fax: +1 8585346046. E-mail address: mxhuang@ucsd.edu (M. Huang). Clinical: Mild (and some moderate) TBI can be difficult to diagnose because the injuries are often not detectable on conventional MRI or CT. There is accumulating evidence that injured brain tissues in TBI patients generate abnormal low-frequency magnetic activity (ALFMA, peaked at 1-4 Hz) that can be measured and localized by magnetoencephalography (MEG). MEG imaging detects TBI abnormalities at the rates of 87% for the mild TBI, group (blast-induced plus non-blast causes) and 100% for the moderate group. Among the mild TBI patients, the rates of abnormalities are 96% and 77% for the blast and non-blast TBI groups, respectively. There is emerging evidence based on fMRI and MEG studies showing hyper-activity in the amygdala and hypo-activity in prefrontal cortex in individuals with PTSD. MEG signal may serve as a sensitive imaging marker for mTBI, distinguishable from abnormalities generated in association with PTSD. More work is needed to fully describe physiological mechanisms of post-concussive symptoms.Published by Elsevier Ltd. BackgroundBlast injuries are deemed the signature wounds of the first wars (Afghanistan and Iraq) of the 21st century (Lancet, 2007;Galarneau et al., 2008). According to a recent U.S. Department Veterans Affairs (DVA) ...

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Section: Clinicalmentioning

confidence: 72%

mentioning

confidence: 91%

The role of biomarkers and MEG-based imaging markers in the diagnosis of post-traumatic stress disorder and blast-induced mild traumatic brain injury

Huang

Risling

Baker

2016

Psychoneuroendocrinology

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“…If boxing is considered a model for detecting "pre-clinical" or asymptomatic brain injury, recent diffusion tensor imaging studies have demonstrated abnormalities in boxers (Chappell et al, 2006;Zhang et al, 2006b). Thus, animal and human studies support the contention of injury on a continuum, implicating that understanding the variables that relate to severity of injury are likely very important in understanding neuropsychological sequelae (see Wilde et al, in press;Lewine et al, 2007).…”

Section: Is Brain Injury On a Continuum: Concussion R Severe Tbi?mentioning

confidence: 93%

Neuropsychology and clinical neuroscience of persistent post-concussive syndrome

Bigler

2007

J Int Neuropsychol Soc

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359

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On the mild end of the acquired brain injury spectrum, the terms concussion and mild traumatic brain injury (mTBI) have been used interchangeably, where persistent post-concussive syndrome (PPCS) has been a label given when symptoms persist for more than three months post-concussion. Whereas a brief history of concussion research is overviewed, the focus of this review is on the current status of PPCS as a clinical entity from the perspective of recent advances in the biomechanical modeling of concussion in human and animal studies, particularly directed at a better understanding of the neuropathology associated with concussion. These studies implicate common regions of injury, including the upper brainstem, base of the frontal lobe, hypothalamic-pituitary axis, medial temporal lobe, fornix, and corpus callosum. Limitations of current neuropsychological techniques for the clinical assessment of memory and executive function are explored and recommendations for improved research designs offered, that may enhance the study of long-term neuropsychological sequelae of concussion. (JINS, 2008, 14, 1-22.)

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“…Furthermore, MEG measures of functional connectivity are comparable to fMRI, but include the additional dimensions of time and oscillatory frequency that are present in neurophysiological data 23. Using a resting state protocol, it has been shown that the location of slow waves in the delta (1–4 Hz) frequency range corresponded to sites of brain injury24, 25 and differentiated individuals with mTBI from controls 26. Functional connectivity metrics acquired from resting state MEG recordings demonstrated decreases in functional connectivity even in mTBI27 and correlated with cognitive recovery and neuropsychological assessments in acquired brain injury 28.…”

Section: Introductionmentioning

confidence: 99%

Reduced brain connectivity and mental flexibility in mild traumatic brain injury

Pang

Dunkley

Doesburg

et al. 2015

Ann Clin Transl Neurol

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ObjectiveA mild traumatic brain injury (mTBI), or concussion, has known neuropsychological sequelae, and neuroimaging shows disturbed brain connectivity during the resting state. We hypothesized that task‐based functional connectivity measures, using magnetoencephalography (MEG), would better link the neurobiological underpinnings of cognitive deficits to specific brain damage.MethodsWe used a mental flexibility task in the MEG and compared brain connectivity between adults with and without mTBI.ResultsAffected individuals showed significant reductions in connectivity. When challenged with a more difficult task, these individuals were not able to “boost” their connectivity, and as such, showed deterioration in performance.InterpretationWe discuss these findings in the context of limitations in cognitive reserve as a consequence of a mTBI.

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Objective Documentation of Traumatic Brain Injury Subsequent to Mild Head Trauma

Abstract: Functional brain imaging data collected in a resting state can provide objective evidence of brain injury in mild blunt head trauma patients with persistent postconcussive somatic and/or cognitive symptoms. MEG proved to be particularly informative for patients with cognitive symptoms.

Cited by 207 publications

References 43 publications

The role of biomarkers and MEG-based imaging markers in the diagnosis of post-traumatic stress disorder and blast-induced mild traumatic brain injury

The role of biomarkers and MEG-based imaging markers in the diagnosis of post-traumatic stress disorder and blast-induced mild traumatic brain injury

Neuropsychology and clinical neuroscience of persistent post-concussive syndrome

Reduced brain connectivity and mental flexibility in mild traumatic brain injury

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