• diffusion tensor imaging
• endogenous pain measure
• mild traumatic brain injury
• post-traumatic headache
• psychological-related assessments

• R01 NS102415 NINDS NIH HHS
• UL1 TR002529 NCATS NIH HHS
• R01 NS112303 NINDS NIH HHS
• R01 AR083130 NIAMS NIH HHS
• UM1 TR004402 NCATS NIH HHS

• McCune-Albright syndrome
• central nervous system
• fibrous dysplasia
• pain
• psychological symptoms

• Humans
• Fibrous Dysplasia, Polyostotic/pathology
• Diffusion Tensor Imaging
• Prospective Studies
• Fibrous Dysplasia of Bone/pathology
• Neuralgia/diagnosis
• Neuralgia/etiology

• MAYDAY Fund and the Boston Children's Hospital CHMC Anesthesia Foundation
• MAYDAY Fund
• Boston Children’s Hospital CHMC Anesthesia Foundation
• NIH

Interest and uptake of science and medicine peer-reviewed literature by readers outside of a paper’s topical subject, field or even discipline is ever-expanding. While the application of knowledge from one field or discipline to others can stimulate innovative solutions to problems facing modern society, it is also fraught with danger for misuse. In the practice of law in the United States, academic papers are submitted to the courts as evidence in personal injury litigation from both the plaintiff (complainant) and defendant. Such transcendence of an academic publication over disciplinary boundaries is immediately met with the challenge of application by a group that inherently lacks in-depth knowledge on the scientific method, the practice of evidence-based medicine, or the publication process as a structured and internationally synthesized process involving peer review and guided by ethical standards and norms. A modern-day example of this is the ongoing conflict between the sensitivity of diffusion tensor imaging (DTI) and the legal standards for admissibility of evidence in litigation cases of mild traumatic brain injury (mTBI). In this review, we amalgamate the peer-reviewed research on DTI in mTBI with the court’s rationale underlying decisions to admit or exclude evidence of DTI abnormalities to support claims of brain injury. We found that the papers which are critical of the use of DTI in the courtroom reflect a primary misunderstanding about how diagnostic biomarkers differ legally from relevant and admissible evidence. The clinical use of DTI to identify white matter abnormalities in the brain at the chronic stage is a valid methodology both clinically as well as forensically, contributes data that may or may not corroborate the existence of white matter damage, and should be admitted into evidence in personal injury trials if supported by a clinician. We also delve into an aspect of science publication and peer review that can be manipulated by scientists and clinicians to publish an opinion piece and misrepresent it as an unbiased, evidence-based, systematic research article in court cases, the decisions of which establish precedence for future cases and have implications on future legislation that will impact the lives of every citizen and erode the integrity of science and medicine practitioners.

• Diffuse axonal injury
• Mild brain injury
• Magnetic resonance imaging
• Neuroimaging
• Medicolegal
• Litigation
• Medical jurisprudence
• Ethics
• Peer review
• Publishing

Cognitive and emotional impairments are frequent among patients with mild traumatic brain injury (mTBI) and may reflect alterations in the brain structural properties. The relationship between microstructural changes and cognitive and emotional deficits remains unclear in patients with mTBI at the acute stage. The purpose of this study was to analyze the alterations in white matter microstructure and connectome of patients with mTBI within 7 days after injury and investigate whether they are related to the clinical questionnaires. A total of 79 subjects (42 mTBI and 37 healthy controls) underwent neuropsychological assessment and diffusion-tensor MRI scan. The microstructure and connectome of white matter were characterized by tract-based spatial statistics (TBSSs) and graph theory approaches, respectively. Mini-mental state examination (MMSE) and self-rating depression scale (SDS) were used to evaluate the cognitive function and depressive symptoms of all the subjects. Patients with mTBI revealed early increases of fractional anisotropy in most areas compared with the healthy controls. Graph theory analyses showed that patients with mTBI had increased nodal shortest path length, along with decreased nodal degree centrality and nodal efficiency, mainly located in the bilateral temporal lobe and right middle occipital gyrus. Moreover, lower nodal shortest path length and higher nodal efficiency of the right middle occipital gyrus were associated with higher SDS scores. Significantly, the strength of the rich club connection in the mTBI group decreased and was associated with the MMSE. Our study demonstrated that the neuroanatomical alterations of mTBI in the acute stage might be an initial step of damage leading to cognitive deficits and depression symptoms, and arguably, these occur due to distinct mechanisms.

• National Natural Science Foundation of China
• Science and Technology Program of Gansu Province

• brainstem
• descending pain modulation
• diffusion tensor imaging
• diffusion tensor tractography
• pain

• DTI
• EEG
• MEG
• fMRI
• phantom limb pain

Background: In attempts to understand the migraine patients’ overall brain functional architecture, blood oxygenation level-dependent (BOLD) signals in the white matter (WM) and gray matter (GM) were considered in the current study. Migraine, a severe and multiphasic brain condition, is characterized by recurrent attacks of headaches. BOLD fluctuations in a resting state exhibit similar temporal and spectral profiles in both WM and GM. It is feasible to explore the functional interactions between WM tracts and GM regions in migraine.

Methods: Forty-eight migraineurs without aura (MWoA) and 48 healthy controls underwent resting-state functional magnetic resonance imaging. Pearson’s correlations between the mean time courses of 48 white matter (WM) bundles and 82 gray matter (GM) regions were computed for each subject. Two-sample t-tests were performed on the Pearson’s correlation coefficients (CC) to compare the differences between the MWoA and healthy controls in the GM-averaged CC of each bundle and the WM-averaged CC of each GM region.

Results: The MWoAs exhibited an overall decreased average temporal CC between BOLD signals in 82 GM regions and 48 WM bundles compared with healthy controls, while little was increased. In particular, WM bundles such as left anterior corona radiata, left external capsule and bilateral superior longitudinal fasciculus had significantly decreased mean CCs with GM in MWoA. On the other hand, 16 GM regions had significantly decreased mean CCs with WM in MWoA, including some areas that are parts of the somatosensory regions, auditory cortex, temporal areas, frontal areas, cingulate cortex, and parietal cortex.

Conclusion: Decreased functional connections between WM bundles and GM regions might contribute to disrupted functional connectivity between the parts of the pain processing pathway in MWoAs, which indicated that functional and connectivity abnormalities in cortical regions may not be limited to GM regions but are instead associated with functional abnormalities in WM tracts.

Mild Traumatic Brain Injury (MTBI) patients with persistent headaches are known to have diminished supraspinal modulatory connectivity from their prefrontal cortices. Repetitive transcranial magnetic stimulation (rTMS) is able to alleviate MTBI-related headache (MTBI-HA). This functional magnetic resonance imaging (fMRI) study assessed supraspinal correlates associated with the headache analgesic effect of rTMS at left prefrontal cortex (LPFC), hypothesizing real rTMS would significantly increase modulatory functions at LPFC in comparison to sham treatment. Subjects with MTBI-HA were randomized to receive either real or sham rTMS treatments and subjected to pre- and post-treatment resting state and evoked heat-pain fMRI as described in a prior study. Real rTMS consisted of 2000 pulses delivered at 10 Hz and 80% of the resting motor threshold at left dorsolateral prefrontal cortex, whereas sham treatment was delivered with same figure-of-eight coil turned 180 degrees. Follow-up fMRI was performed one-week post-treatment. All fMRI data was processed using BrainVoyager QX Software. 14 subjects receiving real and 12 subjects receiving sham treatments completed the study. The REAL group demonstrated significant (P < 0.02) decreases in headache frequency and intensity at one week following treatment. fMRI scans in the REAL group showed increased evoked heat pain activity (P < 0.002) and resting functional connectivity (P < 0.0001) at the LPFC after rTMS. Neither this significant analgesic effect nor these fMRI findings were seen in the sham group. Sham treatment was, however, associated with a decrease in resting state activity at the LPFC (P < 0.0001). This study correlates the demonstrated analgesic effect of rTMS in the treatment of MTBI-HA with enhanced supraspinal functional connectivity in the left prefrontal cortex, which is known to be involved in “top-down” pain inhibition along the descending midbrain-thalamic-cingulate pathway.

Trial Registration: This study was registered on September 24, 2013, on ClinicalTrials.gov with the identifier: NCT01948947. https://clinicaltrials.gov/ct2/show/NCT01948947.

• AUDIT, Alcohol Use Disorders Identification Test-Self Report
• B-IPF, Brief Inventory of Psychosocial Functioning
• CAP, Consortium to Alleviate PTSD
• CAPS-5, Clinician-Administered PTSD Scale for DSM-5
• CBT, cognitive-behavioral therapy
• CCBT, clinic-based cognitive-behavioral therapy intervention for headache
• CEQ, Credibility and Expectancy Questionnaire
• CGRP, calcitonin gene-related peptide
• CPRS, Computerized Patient Record System
• CPT, Cognitive Processing Therapy
• CRIS, Community Reintegration of Injured Service Members
• DRRI-2-D, Deployment Risk and Resilience Inventory-2-Deployment Environment
• DRRI-2-P, Deployment Risk and Resilience Inventory-Postbattle Experiences
• DSI-SS, Depressive Symptom Index-Suicide Subscale
• DoD, U.S. Department of Defense
• GAD-7, Generalized Anxiety Disorder Screener
• GLM, general linear mixed
• HIPAA, Health Insurance Portability and Accountability Act
• HIT-6, Headache Impact Test
• HMSE, Headache Management Self-Efficacy Scale
• HSLC, Headache-Specific Locus of Control Scale
• Headache
• ICHD-2, International Classification of Headache Disorders, 2nd Edition
• ICHD-3, International Classification of Headache Disorders, 3rd Edition
• IRB, institutional review board
• ISI, Insomnia Severity Index
• ITT, intent to treat
• LEC-5, Life Events Checklist for DSM-5
• NIH, National Institutes of Health
• NSI, Neurobehavioral Symptom Inventory
• OSU TBI-ID-SF, Ohio State University TBI Identification Method-Interview Form
• PCL-5, PTSD Checklist for DSM-5
• PHQ-15, Patient Health Questionnaire-15
• PHQ-9, Patient Health Questionnaire-9 Item
• PP, per protocol
• PRC, Polytrauma Rehabilitation Center
• PROMIS, Patient-Reported Outcomes Measurement Information System
• PTCI, Posttraumatic Cognitions Inventory
• PTH, posttraumatic headache
• PTHA Study, posttraumatic headache and PTSD study
• PTSD
• PTSD, posttraumatic stress disorder
• Polymorbidity
• QDS, Quick Drinking Screen
• RSES, Response to Stressful Experiences Scale
• SDIH-R, Structured Diagnostic Interview for Headache-Revised, Brief Version
• SITBI, Self-Injurious Thoughts and Behaviors Interview – Short Form
• STOP, Snoring, Tired, Observed, Blood Pressure
• TAU, treatment as usual
• TBI, traumatic brain injury
• Traumatic brain injury
• VA, U.S. Department of Veterans Affairs
• VHCS, Veterans Health Care System
• VR-12, Veterans RAND 12-Item Health Survey
• Veterans

• MTBI
• chronic post-traumatic headache
• functional magnetic resonance imaging
• pain modulation
• resting state functional activity
• traumatic brain injury

• Brain Concussion/complications
• Brain Concussion/diagnostic imaging
• Headache
• Humans
• Magnetic Resonance Imaging
• Neuralgia
• Pain Perception

• IK2 CX001508 CSRD VA
• I21 RX001359 RRD VA
• I01 CX000842 CSRD VA
• I01 RX002506 RRD VA
• I21 RX002366 RRD VA
• U.S. Department of Veterans Affairs
• U.S. Department of Defense

Objective: Many pieces of research have focused on pain within individuals, but little attention has been paid to whether pain can change an individual’s empathic ability and affect social relationships. The purpose of this study is to explore how chronic low back pain changes empathy.

Methods: Twenty-four chronic low back pain patients and 22 healthy controls were recruited. We set up an experimental pain-exposed model for each healthy subject. All subjects received a painful-empathic magnetic resonance scan. After the scan, all subjects rated the pain intensity and multiple empathy-related indicators. The clinical assessment scale was the 20-item Basic Empathy Scale in Adults.

Result: The chronic low back pain patients reported lower scores on the total scores of BES-A, the subscale scores of emotional disconnection and cognitive empathy, and the discomfort rating. The fMRI results in the chronic low back pain patients showed that there were multiple abnormal brain pathways centered on the anterior insula. The DTI results in the chronic low back pain patients showed that there were reduced fractional anisotropy values in the corpus callosum, bilateral anterior thalamic radiation (ATR), right posterior thalamic radiation (PTR), right superior longitudinal fasciculus (SLF), and left anterior corona radiate (ACR).

Conclusion: Our study found that patients with chronic low back pain have impaired empathy ability. The abnormal functional connectivity of multiple brain networks, multiple damaged white matter tracts, and the lower behavioral scores in chronic low back pain patients supported our findings.

• brain networks
• chronic low back pain
• diffusion tensor imaging
• empathy
• functional magnetic resonance imaging

• Chronic mild TBI related headaches
• Chronic persistent post-traumatic brain injury headache
• MTBI
• MTBI-HA
• Mild traumatic brain injury
• Neuropathic pain state
• PPTH
• Persistent post-traumatic headaches

• Brain Concussion/diagnosis
• Brain Concussion/epidemiology
• Brain Concussion/therapy
• Headache Disorders/diagnosis
• Headache Disorders/epidemiology
• Headache Disorders/therapy
• Humans
• Neuralgia/diagnosis
• Neuralgia/epidemiology
• Neuralgia/therapy
• Prevalence

Post-traumatic headache (PTH) may be considered a secondary headache, which is linked to severe disability and psychosocial impairment. Interestingly, nearly 30% of subjects with persistent post-traumatic headache (PPTH) also suffer from post-traumatic stress disorder (PTSD). Although existing studies demonstrated the existence of common pathophysiological characteristics in subjects with migraine and PPTH, the differences and similarities between these complex diseases are currently poorly understood and are yet to be comprehensively elucidated. Thus, the present review aimed to systematically investigate the nature of PPTH in the effort to better identify both the neurobiological and clinical aspects underlying this condition. Overall, the included studies reported that: (1) the predictors for persistent acute traumatic injury to the head were female gender, persistent symptoms related to mild post-traumatic brain injury (mTBI), PTSD, elevated inflammatory markers, prior mild traumatic brain injury, being injured while suffering from alcohol abuse; (2) static/dynamic functional connectivity differences, white matter tract abnormalities, and morphology changes were found between PPTH and migraine in brain regions involved in pain processing; and (3) clinical differences which were most prominent at early time points when they were linked to the increased risk of PPTH. Based on the selected reports, the relation between migraine and PPTH needs to be considered bidirectionally, but PTSD may play a critical role in this relation. The main implications of these findings, with a specific focus on PTSD, are discussed. Further longitudinal studies are needed to reveal the exact nature of this relation, as well as to clarify the distinct clinical characteristics of migraine, PPTH, and PTSD.

• migraine
• neurovascular response to trauma
• persistent post-traumatic headache
• post-traumatic headache
• psychiatric comorbidity

• Brain Concussion
• Female
• Headache
• Humans
• Migraine Disorders
• Post-Traumatic Headache
• Stress Disorders, Post-Traumatic

• TMS
• acute pain
• headache
• neuropathic pain
• pain
• persistent headache
• post-traumatic brain injury related headache
• primary headaches
• rTMS
• review
• transcranial magnetic stimulation
• treatment recommendation

• brain trauma
• post-concussion syndrome
• post-traumatic headache
• randomized controlled trial
• transcranial magnetic stimulation

• concussion
• functional Near Infrared Spectroscopy (fNIRS)
• post-concussion symptom
• rehabilitation
• transcranial magnetic stimulation (repetitive)