Publications by authors named "Andrew R Mayer"

175 Publications

Early targeted heart rate aerobic exercise versus placebo stretching for sport-related concussion in adolescents: a randomised controlled trial.

Lancet Child Adolesc Health 2021 Sep 30. Epub 2021 Sep 30.

Department of Psychiatry, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.

Background: Sport-related concussion is a public health problem, particularly in adolescents. Quality of life is reduced in adolescents with persistent post-concussive symptoms (symptoms >28 days). We replicated a previous randomised controlled trial to validate the safety, efficacy, and generalisability of, and objective adherence to, prescribed early targeted heart rate subsymptom threshold aerobic exercise compared with placebo-like stretching exercise for adolescent recovery from sport-related concussion and for reducing the risk of persistent post-concussive symptoms.

Methods: This randomised controlled trial was done at three community and hospital-affiliated sports medicine concussion centres in the USA. Male and female adolescent athletes (aged 13-18 years) presenting within 10 days of sport-related concussion were randomly assigned to individualised subsymptom threshold aerobic or stretching exercise at least 20 min daily, for up to 4 weeks after injury. Exercise adherence and intensity were measured by heart rate monitors. The primary outcome was clinical recovery (ie, return to baseline symptoms, normal exercise tolerance, and a normal physical examination) within the 4-week intervention period, and development of persistent post-concussive symptoms beyond 28 days after injury. This study is registered with ClinicalTrials.gov, NCT02959216.

Findings: Between Aug 1, 2018, and March 31, 2020, 118 adolescents were recruited (61 were randomly assigned to the aerobic exercise group and 57 to the stretching exercise group) and included in the intention-to-treat analysis. On survival analysis, controlling for sex, site, and mean daily exercise time, patients assigned to aerobic exercise were more likely to recover within 4 weeks after injury compared with those assigned to stretching exercise, with a 48% reduced risk of persistent post-concussive symptoms (hazard ratio for stretching vs aerobic exercise of 0·52 [95% CI 0·28-0·97], p=0·039). No adverse events were reported.

Interpretation: This multicentre study found that early treatment with subsymptom threshold aerobic exercise safely speeds recovery from sport-related concussion and reduces the risk for persistent post-concussive symptoms, an important result given the impact of delayed recovery on adolescent quality of life. Adherence was good and there were no adverse events from this non-pharmacological treatment. These results suggest that physicians should not only permit, but consider prescribing, early subsymptom threshold physical activity to adolescents as treatment for sport-related concussion and to reduce the risk of persistent post-concussive symptoms.

Funding: American Medical Society for Sports Medicine.
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http://dx.doi.org/10.1016/S2352-4642(21)00267-4DOI Listing
September 2021

Test-Retest Reliability of a Semi-Structured Interview to Aid in Pediatric Traumatic Brain Injury Diagnosis.

J Int Neuropsychol Soc 2021 Aug 11:1-13. Epub 2021 Aug 11.

The Mind Research Network/Lovelace Biomedical Research Institute, Albuquerque, NM, USA.

Objective: Retrospective self-report is typically used for diagnosing previous pediatric traumatic brain injury (TBI). A new semi-structured interview instrument (New Mexico Assessment of Pediatric TBI; NewMAP TBI) investigated test-retest reliability for TBI characteristics in both the TBI that qualified for study inclusion and for lifetime history of TBI.

Method: One-hundred and eight-four mTBI (aged 8-18), 156 matched healthy controls (HC), and their parents completed the NewMAP TBI within 11 days (subacute; SA) and 4 months (early chronic; EC) of injury, with a subset returning at 1 year (late chronic; LC).

Results: The test-retest reliability of common TBI characteristics [loss of consciousness (LOC), post-traumatic amnesia (PTA), retrograde amnesia, confusion/disorientation] and post-concussion symptoms (PCS) were examined across study visits. Aside from PTA, binary reporting (present/absent) for all TBI characteristics exhibited acceptable (≥0.60) test-retest reliability for both Qualifying and Remote TBIs across all three visits. In contrast, reliability for continuous data (exact duration) was generally unacceptable, with LOC and PCS meeting acceptable criteria at only half of the assessments. Transforming continuous self-report ratings into discrete categories based on injury severity resulted in acceptable reliability. Reliability was not strongly affected by the parent completing the NewMAP TBI.

Conclusions: Categorical reporting of TBI characteristics in children and adolescents can aid clinicians in retrospectively obtaining reliable estimates of TBI severity up to a year post-injury. However, test-retest reliability is strongly impacted by the initial data distribution, selected statistical methods, and potentially by patient difficulty in distinguishing among conceptually similar medical concepts (i.e., PTA vs. confusion).
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http://dx.doi.org/10.1017/S1355617721000928DOI Listing
August 2021

Neuroimaging Biomarkers of New-Onset Psychiatric Disorders Following Traumatic Brain Injury.

Biol Psychiatry 2021 Jun 12. Epub 2021 Jun 12.

Department of Psychiatry and Behavioral Sciences, University of New Mexico School of Medicine, Albuquerque, New Mexico.

Traumatic brain injury (TBI) has traditionally been associated with cognitive and behavioral changes during both the acute and chronic phases of injury. Because of its noninvasive nature, neuroimaging has the potential to provide unique information on underlying macroscopic and microscopic biological mechanisms that may serve as causative agents for these neuropsychiatric sequelae. This broad scoping review identifies at least 4 common macroscopic pathways that exist between TBI and new-onset psychiatric disorders, as well as several examples of how neuroimaging is currently being utilized in clinical research. The review then critically examines the strengths and limitations of neuroimaging for elucidating TBI-related microscopic pathology, such as microstructural changes, neuroinflammation, proteinopathies, blood-brain barrier damage, and disruptions in cellular signaling. A summary is then provided for how neuroimaging is currently being used to investigate TBI-related pathology in new-onset neurocognitive disorders, depression, and posttraumatic stress disorder. Identified gaps in the literature include a lack of prospective studies to definitively associate imaging findings with the development of new-onset psychiatric disorders, as well as antemortem imaging studies subsequently confirmed with postmortem correlates in the same study cohort. Although the spatial resolution and specificity of imaging biomarkers has greatly improved over the last 2 decades, we conclude that neuroimaging biomarkers do not yet exist for the definitive in vivo diagnosis of cellular pathology. This represents a necessary next step for further elucidating causal relationships between TBI and new-onset psychiatric disorders.
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http://dx.doi.org/10.1016/j.biopsych.2021.06.005DOI Listing
June 2021

DNA methylation under the major depression pathway predicts pediatric quality of life four-month post-pediatric mild traumatic brain injury.

Clin Epigenetics 2021 Jul 12;13(1):140. Epub 2021 Jul 12.

Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, Emory University, 55 Park Place NE, 18th Floor, Atlanta, GA, 30303, USA.

Background: Major depression has been recognized as the most commonly diagnosed psychiatric complication of mild traumatic brain injury (mTBI). Moreover, major depression is associated with poor outcomes following mTBI; however, the underlying biological mechanisms of this are largely unknown. Recently, genomic and epigenetic factors have been increasingly implicated in the recovery following TBI.

Results: This study leveraged DNA methylation within the major depression pathway, along with demographic and behavior measures (features used in the clinical model) to predict post-concussive symptom burden and quality of life four-month post-injury in a cohort of 110 pediatric mTBI patients and 87 age-matched healthy controls. The results demonstrated that including DNA methylation markers in the major depression pathway improved the prediction accuracy for quality of life but not persistent post-concussive symptom burden. Specifically, the prediction accuracy (i.e., the correlation between the predicted value and observed value) of quality of life was improved from 0.59 (p = 1.20 × 10) (clinical model) to 0.71 (p = 3.89 × 10); the identified cytosine-phosphate-guanine sites were mainly in the open sea regions and the mapped genes were related to TBI in several molecular studies. Moreover, depression symptoms were a strong predictor (with large weights) for both post-concussive symptom burden and pediatric quality of life.

Conclusion: This study emphasized that both molecular and behavioral manifestations of depression symptoms played a prominent role in predicting the recovery process following pediatric mTBI, suggesting the urgent need to further study TBI-caused depression symptoms for better recovery outcome.
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http://dx.doi.org/10.1186/s13148-021-01128-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274037PMC
July 2021

Reproducibility and Characterization of Head Kinematics During a Large Animal Acceleration Model of Traumatic Brain Injury.

Front Neurol 2021 9;12:658461. Epub 2021 Jun 9.

Enroute Care Group, U.S. Army Aeromedical Research Laboratory, Fort Rucker, AL, United States.

Acceleration parameters have been utilized for the last six decades to investigate pathology in both human and animal models of traumatic brain injury (TBI), design safety equipment, and develop injury thresholds. Previous large animal models have quantified acceleration from impulsive loading forces (i.e., machine/object kinematics) rather than directly measuring head kinematics. No study has evaluated the reproducibility of head kinematics in large animal models. Nine (five males) sexually mature Yucatan swine were exposed to head rotation at a targeted peak angular velocity of 250 rad/s in the coronal plane. The results indicated that the measured peak angular velocity of the skull was 51% of the impulsive load, was experienced over 91% longer duration, and was multi- rather than uni-planar. These findings were replicated in a second experiment with a smaller cohort ( = 4). The reproducibility of skull kinematics data was mostly within acceptable ranges based on published industry standards, although the coefficients of variation (8.9% for peak angular velocity or 12.3% for duration) were higher than the impulsive loading parameters produced by the machine (1.1 vs. 2.5%, respectively). Immunohistochemical markers of diffuse axonal injury and blood-brain barrier breach were not associated with variation in either skull or machine kinematics, suggesting that the observed levels of variance in skull kinematics may not be biologically meaningful with the current sample sizes. The findings highlight the reproducibility of a large animal acceleration model of TBI and the importance of direct measurements of skull kinematics to determine the magnitude of angular velocity, refine injury criteria, and determine critical thresholds.
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http://dx.doi.org/10.3389/fneur.2021.658461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219951PMC
June 2021

A Commentary on Silverberg and the Many Expert Panel Definitions of Mild Head Injury.

Authors:
Andrew R Mayer

Arch Phys Med Rehabil 2021 06;102(6):1238-1239

The Mind Research Network/Lovelace Biomedical Research Institute, Albuquerque, MN; Neurology, Psychiatry, and Psychology Departments, University of New Mexico School of Medicine, Albuquerque, NM.

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http://dx.doi.org/10.1016/j.apmr.2021.01.088DOI Listing
June 2021

Reward Processing in Novelty Seekers: A Transdiagnostic Psychiatric Imaging Biomarker.

Biol Psychiatry 2021 Oct 30;90(8):529-539. Epub 2021 Jan 30.

Centre for Population Neuroscience and Stratified Medicine, Institute for Science and Technology of Brain-Inspired Intelligence, Fudan University, Shanghai, China.

Background: Dysfunctional reward processing is implicated in multiple mental disorders. Novelty seeking (NS) assesses preference for seeking novel experiences, which is linked to sensitivity to reward environmental cues.

Methods: A subset of 14-year-old adolescents (IMAGEN) with the top 20% ranked high-NS scores was used to identify high-NS-associated multimodal components by supervised fusion. These features were then used to longitudinally predict five different risk scales for the same and unseen subjects (an independent dataset of subjects at 19 years of age that was not used in predictive modeling training at 14 years of age) (within IMAGEN, n ≈1100) and even for the corresponding symptom scores of five types of patient cohorts (non-IMAGEN), including drinking (n = 313), smoking (n = 104), attention-deficit/hyperactivity disorder (n = 320), major depressive disorder (n = 81), and schizophrenia (n = 147), as well as to classify different patient groups with diagnostic labels.

Results: Multimodal biomarkers, including the prefrontal cortex, striatum, amygdala, and hippocampus, associated with high NS in 14-year-old adolescents were identified. The prediction models built on these features are able to longitudinally predict five different risk scales, including alcohol drinking, smoking, hyperactivity, depression, and psychosis for the same and unseen 19-year-old adolescents and even predict the corresponding symptom scores of five types of patient cohorts. Furthermore, the identified reward-related multimodal features can classify among attention-deficit/hyperactivity disorder, major depressive disorder, and schizophrenia with an accuracy of 87.2%.

Conclusions: Adolescents with higher NS scores can be used to reveal brain alterations in the reward-related system, implicating potential higher risk for subsequent development of multiple disorders. The identified high-NS-associated multimodal reward-related signatures may serve as a transdiagnostic neuroimaging biomarker to predict disease risks or severity.
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http://dx.doi.org/10.1016/j.biopsych.2021.01.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322149PMC
October 2021

Ventromedial Prefrontal-Anterior Cingulate Hyperconnectivity and Resilience to Apathy in Traumatic Brain Injury.

J Neurotrauma 2021 Aug 10;38(16):2264-2274. Epub 2021 Jun 10.

Department of Psychiatry and Behavioral Sciences, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.

Apathy is a common and impairing sequela of traumatic brain injury (TBI). Yet, little is known about the neural mechanisms determining in which patients apathy does or does not develop post-TBI. We aimed to elucidate the impact of TBI on motivational neural circuits and how this shapes apathy over the course of TBI recovery. Resting-state functional magnetic resonance imaging data were collected in patients with subacute mild TBI ( = 44), chronic mild-to-moderate TBI ( = 26), and nonbrain-injured control participants (CTRL;  = 28). We measured ventromedial prefrontal cortex (vmPFC) functional connectivity (FC) as a function of apathy, using an vmPFC seed adopted from a motivated decision-making study in an independent TBI study cohort. Patients reported apathy using a well-validated tool for assaying apathy in TBI. The vmPFC-to-wholebrain FC was contrasted between groups, and we fit regression models with apathy predicting vmPFC FC. Subacute and chronic TBI caused increased apathy relative to CTRL, replicating previous work suggesting that apathy has an enduring impact in TBI. The vmPFC was functionally connected to the canonical default network, and this architecture did not differ between subacute TBI, chronic TBI, and CTRL groups. Critically, in TBI, increased apathy scores predicted decreased vmPFC-dorsal anterior cingulate cortex (dACC) FC. Last, we subdivided the TBI group based on patients above versus below the threshold for "clinically significant apathy," finding that TBI patients with clinically significant apathy demonstrated comparable vmPFC-dACC FC to CTRLs, whereas TBI patients with subthreshold apathy scores demonstrated vmPFC-dACC hyperconnectivity relative to both CTRLs and patients with clinically significant apathy. Post-TBI vmPFC-dACC hyperconnectivity may represent an adaptive compensatory response, helping to maintain motivation and enabling resilience to the development of apathy after neurotrauma. Given the role of vmPFC-dACC circuits in value-based decision making, rehabilitation strategies designed to improve this ability may help to reduce apathy and improve functional outcomes in TBI.
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http://dx.doi.org/10.1089/neu.2020.7363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328044PMC
August 2021

The clinical relevance of gray matter atrophy and microstructural brain changes across the psychosis continuum.

Schizophr Res 2021 03 17;229:12-21. Epub 2021 Feb 17.

The Mind Research Network/Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM 87106, USA; Department of Psychiatry, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA; Department of Psychology, University of New Mexico, Albuquerque, NM 87131, USA; Department of Neurology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA. Electronic address:

Patients with psychotic spectrum disorders (PSD) exhibit similar patterns of atrophy and microstructural changes that may be associated with common symptomatology (e.g., symptom burden and/or cognitive impairment). Gray matter concentration values (proxy for atrophy), fractional anisotropy (FA), mean diffusivity (MD), intracellular neurite density (V) and isotropic diffusion volume (V) measures were therefore compared in 150 PSD (schizophrenia, schizoaffective disorder, and bipolar disorder Type I) and 63 healthy controls (HC). Additional analyses evaluated whether regions showing atrophy and/or microstructure abnormalities were better explained by DSM diagnoses, symptom burden or cognitive dysfunction. PSD exhibited increased atrophy within bilateral medial temporal lobes and subcortical structures. Gray matter along the left lateral sulcus showed evidence of increased atrophy and MD. Increased MD was also observed in homotopic fronto-temporal regions, suggesting it may serve as a precursor to atrophic changes. Global cognitive dysfunction, rather than DSM diagnoses or psychotic symptom burden, was the best predictor of increased gray matter MD. Regions of decreased FA (i.e., left frontal gray and white matter) and V (i.e., frontal and temporal regions and along central sulcus) were also observed for PSD, but were neither spatially concurrent with atrophic regions nor associated with clinical symptoms. Evidence of expanding microstructural spaces in gray matter demonstrated the greatest spatial overlap with current and potentially future regions of atrophy, and was associated with cognitive deficits. These results suggest that this particular structural abnormality could potentially underlie global cognitive impairment that spans traditional diagnostic categories.
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http://dx.doi.org/10.1016/j.schres.2021.01.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137524PMC
March 2021

Symptoms upon postural change and orthostatic hypotension in adolescents with concussion.

Brain Inj 2021 01 17;35(2):226-232. Epub 2021 Jan 17.

UBMD Department of Orthopaedics and Sports Medicine, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, USA.

: Concussion is associated with dysautonomia, altered blood pressure (BP) control, and may cause Orthostatic Hypotension (OH). We measured prevalence of OH using the 1-minute supine-to-standing OH Test in adolescents with concussion and controls.: Adolescents within 10 days of injury (Concussion Group, n = 297, 15.0 ± 1.7 years, 59% male) were compared with controls (Control Group, n = 214, 15.0 ± 1.5 years, 58% male).: BP, heart rate (HR), and complaints of lightheadedness/dizziness were measured after 2-minute supine and 1-minute standing. Control Group was assessed once. Concussion Group was assessed twice; (1) initial visit (mean 6.0 ± 3 days-since-injury) and (2) after clinical recovery (mean 46.3 ± 42 days-since-injury).: Initial visit; Concussion Group reported feeling lightheaded/dizzy on postural change more often than the Control Group (37% vs 4%,  < .001) but did not differ in meeting standard OH criteria (3% vs 5%,  = .32). Experiencing symptoms did not correlate with meeting OH criteria, but correlated with abnormal vestibulo-ocular reflex. After clinical recovery; Concussion Group did not differ in experiencing lightheaded/dizziness on postural change than controls (4%,  = .65).: Adolescents commonly experience orthostatic intolerance after concussion without meeting the standard criteria for OH.
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http://dx.doi.org/10.1080/02699052.2021.1871951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033637PMC
January 2021

Association of Previous Concussion with Hippocampal Volume and Symptoms in Collegiate-Aged Athletes.

J Neurotrauma 2021 May 16;38(10):1358-1367. Epub 2021 Feb 16.

Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

There is concern that previous concussion and contact-sport exposure may have negative effects on brain structure and function. Accurately quantifying previous concussion is complicated by the fact that multiple definitions exist, with recent definitions allowing for diagnosis based on the presence of symptoms alone (Concussion in Sport Group criteria; CISG) rather than the presence of acute injury characteristics such as alterations in mental status (American Congress of Rehabilitation Medicine criteria; ACRM). The goals of the current work were to determine the effects of previous concussion and contact-sport exposure on gray matter structure and clinical measures in healthy, young-adult athletes and determine the extent to which these associations are influenced by diagnostic criteria used to retrospectively quantify concussions. One-hundred eight collegiate-aged athletes were enrolled; 106 athletes were included in final analyses (age, 21.37 ± 1.69; 33 female). Participants completed a clinical battery of self-report and neurocognitive measures and magnetic resonance imaging to quantify subcortical volumes and cortical thickness. Semistructured interviews were conducted to measure exposure to contact sports and the number of previous concussions based on CISG and ACRM criteria. There was a significant association of concussion-related and psychological symptoms with previous concussions based on ACRM (s < 0.05), but not CISG, criteria. Hippocampal volume was inversely associated with the number of previous concussions for both criteria (s < 0.05). Findings provide evidence that previous concussions are associated with smaller hippocampal volumes and greater subjective clinical symptoms in otherwise healthy athletes and highlight the importance of diagnostic criteria used to quantify previous concussion.
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http://dx.doi.org/10.1089/neu.2020.7143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082726PMC
May 2021

Use of Medical Cannabis to Treat Traumatic Brain Injury.

J Neurotrauma 2021 Jul 25;38(14):1904-1917. Epub 2021 Jan 25.

The Mind Research Network/Lovelace Biomedical and Environmental Research Institute, Pete & Nancy Domenici Hall, Albuquerque, New Mexico, USA.

There is not a single pharmacological agent with demonstrated therapeutic efficacy for traumatic brain injury (TBI). With recent legalization efforts and the growing popularity of medical cannabis, patients with TBI will inevitably consider medical cannabis as a treatment option. Pre-clinical TBI research suggests that cannabinoids have neuroprotective and psychotherapeutic properties. In contrast, recreational cannabis use has consistently shown to have detrimental effects. Our review identified a paucity of high-quality studies examining the beneficial and adverse effects of medical cannabis on TBI, with only a single phase III randomized control trial. However, observational studies demonstrate that TBI patients are using medical and recreational cannabis to treat their symptoms, highlighting inconsistencies between public policy, perception of potential efficacy, and the dearth of empirical evidence. We conclude that randomized controlled trials and prospective studies with appropriate control groups are necessary to fully understand the efficacy and potential adverse effects of medical cannabis for TBI.
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http://dx.doi.org/10.1089/neu.2020.7148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260892PMC
July 2021

Severity of Ongoing Post-Concussive Symptoms as a Predictor of Cognitive Performance Following a Pediatric Mild Traumatic Brain Injury.

J Int Neuropsychol Soc 2021 08 27;27(7):686-696. Epub 2020 Nov 27.

The Mind Research Network/Lovelace Biomedical Research Institute, Albuquerque, NM, USA.

Objective: This study aimed to examine the predictors of cognitive performance in patients with pediatric mild traumatic brain injury (pmTBI) and to determine whether group differences in cognitive performance on a computerized test battery could be observed between pmTBI patients and healthy controls (HC) in the sub-acute (SA) and the early chronic (EC) phases of injury.

Method: 203 pmTBI patients recruited from emergency settings and 159 age- and sex-matched HC aged 8-18 rated their ongoing post-concussive symptoms (PCS) on the Post-Concussion Symptom Inventory and completed the Cogstate brief battery in the SA (1-11 days) phase of injury. A subset (156 pmTBI patients; 144 HC) completed testing in the EC (~4 months) phase.

Results: Within the SA phase, a group difference was only observed for the visual learning task (One-Card Learning), with pmTBI patients being less accurate relative to HC. Follow-up analyses indicated higher ongoing PCS and higher 5P clinical risk scores were significant predictors of lower One-Card Learning accuracy within SA phase, while premorbid variables (estimates of intellectual functioning, parental education, and presence of learning disabilities or attention-deficit/hyperactivity disorder) were not.

Conclusions: The absence of group differences at EC phase is supportive of cognitive recovery by 4 months post-injury. While the severity of ongoing PCS and the 5P score were better overall predictors of cognitive performance on the Cogstate at SA relative to premorbid variables, the full regression model explained only 4.1% of the variance, highlighting the need for future work on predictors of cognitive outcomes.
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http://dx.doi.org/10.1017/S1355617720001228DOI Listing
August 2021

Mind-body (hypnotherapy) treatment of women with urgency urinary incontinence: changes in brain attentional networks.

Am J Obstet Gynecol 2021 05 26;224(5):498.e1-498.e10. Epub 2020 Oct 26.

Mind Research Network, Albuquerque, New Mexico.

Background: Prior study of patients with urgency urinary incontinence by functional magnetic resonance imaging showed altered function in areas of the brain associated with interoception and salience and with attention. Our randomized controlled trial of hypnotherapy for urgency urinary incontinence demonstrated marked improvement in urgency urinary incontinence symptoms at 2 months. A subsample of these women with urgency urinary incontinence underwent functional magnetic resonance imaging before and after treatment.

Objective: This study aimed to determine if hypnotherapy treatment of urgency urinary incontinence compared with pharmacotherapy was associated with altered brain activation or resting connectivity on functional magnetic resonance imaging.

Study Design: A subsample of women participating in a randomized controlled trial comparing hypnotherapy vs pharmacotherapy for treatment of urgency urinary incontinence was evaluated with functional magnetic resonance imaging. Scans were obtained pretreatment and 8 to 12 weeks after treatment initiation. Brain activation during bladder filling and resting functional connectivity with an empty and partially filled bladder were assessed. Brain regions of interest were derived from those previously showing differences between healthy controls and participants with untreated urgency urinary incontinence in our prior work and included regions in the interoceptive and salience, ventral attentional, and dorsal attentional networks.

Results: After treatment, participants in both groups demonstrated marked improvement in incontinence episodes (P<.001). Bladder-filling task functional magnetic resonance imaging data from the combined groups (n=64, 30 hypnotherapy, 34 pharmacotherapy) demonstrated decreased activation of the left temporoparietal junction, a component of the ventral attentional network (P<.01) compared with baseline. Resting functional connectivity differed only with the bladder partially filled (n=54). Compared with pharmacotherapy, hypnotherapy participants manifested increased functional connectivity between the anterior cingulate cortex and the left dorsolateral prefrontal cortex, a component of the dorsal attentional network (P<.001).

Conclusion: Successful treatment of urgency urinary incontinence with both pharmacotherapy and hypnotherapy was associated with decreased activation of the ventral (bottom-up) attentional network during bladder filling. This may be attributable to decreased afferent stimuli arising from the bladder in the pharmacotherapy group. In contrast, decreased ventral attentional network activation associated with hypnotherapy may be mediated by the counterbalancing effects of the dorsal (top-down) attentional network.
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http://dx.doi.org/10.1016/j.ajog.2020.10.041DOI Listing
May 2021

Cerebral Perfusion Effects of Cognitive Training and Transcranial Direct Current Stimulation in Mild-Moderate TBI.

Front Neurol 2020 7;11:545174. Epub 2020 Oct 7.

Mind Research Network, Albuquerque, NM, United States.

Persistent post-traumatic symptoms (PPS) after traumatic brain injury (TBI) can lead to significant chronic functional impairment. Pseudocontinuous arterial spin labeling (pCASL) has been used in multiple studies to explore changes in cerebral blood flow (CBF) that may result in acute and chronic TBI, and is a promising neuroimaging modality for assessing response to therapies. Twenty-four subjects with chronic mild-moderate TBI (mmTBI) were enrolled in a pilot study of 10 days of computerized executive function training combined with active or sham anodal transcranial direct current stimulation (tDCS) for treatment of cognitive PPS. Behavioral surveys, neuropsychological testing, and magnetic resonance imaging (MRI) with pCASL sequences to assess global and regional CBF were obtained before and after the training protocol. Robust improvements in depression, anxiety, complex attention, and executive function were seen in both active and sham groups between the baseline and post-treatment visits. Global CBF decreased over time, with differences in regional CBF noted in the right inferior frontal gyrus (IFG). Active stimulation was associated with static or increased CBF in the right IFG, whereas sham was associated with reduced CBF. Neuropsychological performance and behavioral symptoms were not associated with changes in CBF. The current study suggests a complex picture between mmTBI, cerebral perfusion, and recovery. Changes in CBF may result from physiologic effect of the intervention, compensatory neural mechanisms, or confounding factors. Limitations include a small sample size and heterogenous injury sample, but these findings suggest promising directions for future studies of cognitive training paradigms in mmTBI.
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http://dx.doi.org/10.3389/fneur.2020.545174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575722PMC
October 2020

Prospective study of the association between sport-related concussion and brain morphometry (3T-MRI) in collegiate athletes: study from the NCAA-DoD CARE Consortium.

Br J Sports Med 2021 Feb 11;55(3):169-174. Epub 2020 Sep 11.

Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA

Objectives: To determine the acute and early long-term associations of sport-related concussion (SRC) and subcortical and cortical structures in collegiate contact sport athletes.

Methods: Athletes with a recent SRC (n=99) and matched contact (n=91) and non-contact sport controls (n=95) completed up to four neuroimaging sessions from 24 to 48 hours to 6 months postinjury. Subcortical volumes (amygdala, hippocampus, thalamus and dorsal striatum) and vertex-wise measurements of cortical thickness/volume were computed using FreeSurfer. Linear mixed-effects models examined the acute and longitudinal associations between concussion and structural metrics, controlling for intracranial volume (or mean thickness) and demographic variables (including prior concussions and sport exposure).

Results: There were significant group-dependent changes in amygdala volumes across visits (p=0.041); this effect was driven by a trend for increased amygdala volume at 6 months relative to subacute visits in contact controls, with no differences in athletes with SRC. No differences were observed in any cortical metric (ie, thickness or volume) for primary or secondary analyses.

Conclusion: A single SRC had minimal associations with grey matter structure across a 6-month time frame.
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http://dx.doi.org/10.1136/bjsports-2020-102002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855484PMC
February 2021

Survival Rates and Biomarkers in a Large Animal Model of Traumatic Brain Injury Combined With Two Different Levels of Blood Loss.

Shock 2021 04;55(4):554-562

Enroute Care Group, U.S. Army Aeromedical Research Laboratory, Fort Rucker, Alabama.

Introduction: The pathology resulting from concurrent traumatic brain injury (TBI) and hemorrhagic shock (HS; TBI+HS) are leading causes of mortality and morbidity worldwide following trauma. However, the majority of large animal models of TBI+HS have utilized focal/contusional injuries rather than incorporating the types of brain trauma (closed-head injury caused by dynamic acceleration) that typify human injury.

Objective: To examine survival rates and effects on biomarkers from rotational TBI with two levels of HS.

Methods: Twenty-two sexually mature Yucatan swine (30.39 ± 2.25 kg; 11 females) therefore underwent either Sham trauma procedures (n = 6) or a dynamic acceleration TBI combined with either 55% (n = 8) or 40% (n = 8) blood loss in this serial study.

Results: Survival rates were significantly higher for the TBI+40% (87.5%) relative to TBI+55% (12.5%) cohort, with the majority of TBI+55% animals expiring within 2 h post-trauma from apnea. Blood-based neural biomarkers and immunohistochemistry indicated evidence of diffuse axonal injury (increased NFL/Aβ42), blood-brain barrier breach (increased immunoglobulin G) and inflammation (increased glial fibrillary acidic protein/ionized calcium-binding adaptor molecule 1) in the injured cohorts relative to Shams. Invasive hemodynamic measurements indicated increased shock index and decreased pulse pressure in both injury cohorts, with evidence of partial recovery for invasive hemodynamic measurements in the TBI+40% cohort. Similarly, although both injury groups demonstrated ionic and blood gas abnormalities immediately postinjury, metabolic acidosis continued to increase in the TBI+55% group ∼85 min postinjury. Somewhat surprisingly, both neural and physiological biomarkers showed significant changes within the Sham cohort across the multi-hour experimental procedure, most likely associated with prolonged anesthesia.

Conclusion: Current results suggest the TBI+55% model may be more appropriate for severe trauma requiring immediate medical attention/standard fluid resuscitation protocols whereas the TBI+40% model may be useful for studies of prolonged field care.
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http://dx.doi.org/10.1097/SHK.0000000000001653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112147PMC
April 2021

Differing functional mechanisms underlie cognitive control deficits in psychotic spectrum disorders.

J Psychiatry Neurosci 2020 11;45(6):430-440

From the The Mind Research Network/Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM (Stephenson, Shaikh, Shaff, Dodd, Wertz, Ryman, Hanlon, Ling, Mayer); the Department of Psychiatry, University of New Mexico School of Medicine, Albuquerque, NM (Bustillo, Stromberg, Lin, Abrams, Mayer); the Department of Psychology, University of New Mexico, Albuquerque, NM (Hogeveen, Yeo, Mayer); and the Department of Neurology, University of New Mexico School of Medicine, Albuquerque, NM (Mayer).

Background: Functional underpinnings of cognitive control deficits in unbiased samples (i.e., all comers) of patients with psychotic spectrum disorders (PSD) remain actively debated. While many studies suggest hypofrontality in the lateral prefrontal cortex (PFC) and greater deficits during proactive relative to reactive control, few have examined the full hemodynamic response.

Methods: Patients with PSD (n = 154) and healthy controls (n = 65) performed the AX continuous performance task (AX-CPT) during rapid (460 ms) functional neuroimaging and underwent full clinical characterization.

Results: Behavioural results indicated generalized cognitive deficits (slower and less accurate) across proactive and reactive control conditions in patients with PSD relative to healthy controls. We observed a delayed/prolonged neural response in the left dorsolateral PFC, the sensorimotor cortex and the superior parietal lobe during proactive control for patients with PSD. These proactive hemodynamic abnormalities were better explained by negative rather than by positive symptoms or by traditional diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR), with subsequent simulations unequivocally demonstrating how these abnormalities could be erroneously interpreted as hypoactivation. Conversely, true hypoactivity, unassociated with clinical symptoms or DSM-IV-TR diagnoses, was observed within the ventrolateral PFC during reactive control.

Limitations: In spite of guidance for AX-CPT use in neuroimaging studies, one-third of patients with PSD could not perform the task above chance and were more clinically impaired.

Conclusion: Current findings question the utility of the AX-CPT for neuroimaging-based appraisal of cognitive control across the full spectrum of patients with PSD. Previously reported lateral PFC "hypoactivity" during proactive control may be more indicative of a delayed/prolonged neural response, important for rehabilitative purposes. Negative symptoms may better explain certain behavioural and hemodynamic abnormalities in patients with PSD relative to DSM-IV-TR diagnoses.
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http://dx.doi.org/10.1503/jpn.190212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595736PMC
November 2020

Cumulative Effects of Prior Concussion and Primary Sport Participation on Brain Morphometry in Collegiate Athletes: A Study From the NCAA-DoD CARE Consortium.

Front Neurol 2020 28;11:673. Epub 2020 Jul 28.

Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, United States.

Prior studies have reported long-term differences in brain structure (brain morphometry) as being associated with cumulative concussion and contact sport participation. There is emerging evidence to suggest that similar effects of prior concussion and contact sport participation on brain morphometry may be present in younger cohorts of active athletes. We investigated the relationship between prior concussion and primary sport participation with subcortical and cortical structures in active collegiate contact sport and non-contact sport athletes. Contact sport athletes (CS; = 190) and matched non-contact sport athletes (NCS; = 95) completed baseline clinical testing and participated in up to four serial neuroimaging sessions across a 6-months period. Subcortical and cortical structural metrics were derived using FreeSurfer. Linear mixed-effects (LME) models examined the effects of years of primary sport participation and prior concussion (0, 1+) on brain structure and baseline clinical variables. Athletes with prior concussion across both groups reported significantly more baseline concussion and psychological symptoms (all s < 0.05). The relationship between years of primary sport participation and thalamic volume differed between CS and NCS ( = 0.015), driven by a significant inverse association between primary years of participation and thalamic volume in CS ( = 0.007). Additional analyses limited to CS alone showed that the relationship between years of primary sport participation and dorsal striatal volume was moderated by concussion history ( = 0.042). Finally, CS with prior concussion had larger hippocampal volumes than CS without prior concussion ( = 0.015). Years of contact sport exposure and prior concussion(s) are associated with differences in subcortical volumes in young-adult, active collegiate athletes, consistent with prior literature in retired, primarily symptomatic contact sport athletes. Longitudinal follow-up studies in these athletes are needed to determine clinical significance of current findings.
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http://dx.doi.org/10.3389/fneur.2020.00673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399344PMC
July 2020

The ENIGMA sports injury working group:- an international collaboration to further our understanding of sport-related brain injury.

Brain Imaging Behav 2021 Apr;15(2):576-584

H. Ben Taub Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, TX, USA.

Sport-related brain injury is very common, and the potential long-term effects include a wide range of neurological and psychiatric symptoms, and potentially neurodegeneration. Around the globe, researchers are conducting neuroimaging studies on primarily homogenous samples of athletes. However, neuroimaging studies are expensive and time consuming, and thus current findings from studies of sport-related brain injury are often limited by small sample sizes. Further, current studies apply a variety of neuroimaging techniques and analysis tools which limit comparability among studies. The ENIGMA Sports Injury working group aims to provide a platform for data sharing and collaborative data analysis thereby leveraging existing data and expertise. By harmonizing data from a large number of studies from around the globe, we will work towards reproducibility of previously published findings and towards addressing important research questions with regard to diagnosis, prognosis, and efficacy of treatment for sport-related brain injury. Moreover, the ENIGMA Sports Injury working group is committed to providing recommendations for future prospective data acquisition to enhance data quality and scientific rigor.
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http://dx.doi.org/10.1007/s11682-020-00370-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855299PMC
April 2021

Longitudinal white-matter abnormalities in sports-related concussion: A diffusion MRI study.

Neurology 2020 08 8;95(7):e781-e792. Epub 2020 Jul 8.

From the Departments of Radiology and Imaging Sciences (Y.-C.W., N.M.H.E., Q.W., S.M.M., A.J.S.), Psychiatry (Z.L., T.W.M.), and Biostatistics (L.D.R.), Indiana University School of Medicine, Indianapolis; Department of Epidemiology and Biostatistics (J.H.), School of Public Health, Indiana University, Bloomington; Nanoscope Technology LLC (S.M.M.), Bedford, TX; Departments of Radiology (K.M.K., A.S.N., Y.W.) and Neurosurgery (T.B.M., M.A.M.), Medical College of Wisconsin, Milwaukee; The Mind Research Network (A.R.M.), Albuquerque, NM; Department of Neurosurgery (C.C.G.), David Geffen School of Medicine at the University of California Los Angeles; Division of Pediatric Neurology (C.C.G.), Mattel Children's Hospital-UCLA; Departments of Family Medicine and Orthopedics (J.P.D.), Division of Sports Medicine, University of California Los Angeles; Primary Care Sports Medicine (J.P.D.), Hospital for Special Surgery, New York, NY; Matthew Gfeller Sport-Related Traumatic Brain Injury Research Center (K.M.G., J.P.M.), Department of Exercise and Sport Science, University of North Carolina, Chapel Hill; School of Biomedical Engineering and Sciences (S.M.L.), Wake-Forest and Virginia Tech University, Virginia Tech Carilion Research Institute, Roanoke; School of Biomedical Engineering and Sciences (S.M.D.), Wake-Forest and Virginia Tech University, Blacksburg; and NeuroTrauma Research Laboratory (S.P.B.), Michigan Concussion Center, University of Michigan, Ann Arbor.

Objective: To study longitudinal recovery trajectories of white matter after sports-related concussion (SRC) by performing diffusion tensor imaging (DTI) on collegiate athletes who sustained SRC.

Methods: Collegiate athletes (n = 219, 82 concussed athletes, 68 contact-sport controls, and 69 non-contact-sport controls) were included from the Concussion Assessment, Research and Education Consortium. The participants completed clinical assessments and DTI at 4 time points: 24 to 48 hours after injury, asymptomatic state, 7 days after return-to-play, and 6 months after injury. Tract-based spatial statistics was used to investigate group differences in DTI metrics and to identify white-matter areas with persistent abnormalities. Generalized linear mixed models were used to study longitudinal changes and associations between outcome measures and DTI metrics. Cox proportional hazards model was used to study effects of white-matter abnormalities on recovery time.

Results: In the white matter of concussed athletes, DTI-derived mean diffusivity was significantly higher than in the controls at 24 to 48 hours after injury and beyond the point when the concussed athletes became asymptomatic. While the extent of affected white matter decreased over time, part of the corpus callosum had persistent group differences across all the time points. Furthermore, greater elevation of mean diffusivity at acute concussion was associated with worse clinical outcome measures (i.e., Brief Symptom Inventory scores and symptom severity scores) and prolonged recovery time. No significant differences in DTI metrics were observed between the contact-sport and non-contact-sport controls.

Conclusions: Changes in white matter were evident after SRC at 6 months after injury but were not observed in contact-sport exposure. Furthermore, the persistent white-matter abnormalities were associated with clinical outcomes and delayed recovery time.
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http://dx.doi.org/10.1212/WNL.0000000000009930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605507PMC
August 2020

Resting-State Power and Regional Connectivity After Pediatric Mild Traumatic Brain Injury.

J Magn Reson Imaging 2020 12 27;52(6):1701-1713. Epub 2020 Jun 27.

The Mind Research Network/LBERI, Albuquerque, New Mexico, USA.

Background: Physiological recovery from pediatric mild traumatic brain injury (pmTBI) as a function of age remains actively debated, with the majority of studies relying on subjective symptom report rather than objective markers of brain physiology.

Purpose: To examine potential abnormalities in fractional amplitude of low-frequency fluctuations (fALFF) or regional homogeniety (ReHo) during resting-state fMRI following pmTBI.

Study Type: Prospective cohort.

Population: Consecutively recruited pmTBI (N = 105; 8-18 years old) and age- and sex-matched healthy controls (HC; N = 113).

Field Strength/sequence: 3T multiecho gradient T -weighted and single-shot gradient-echo echo-planar imaging.

Assessment: All pmTBI participants were assessed 1 week and 4 months postinjury (HC assessed at equivalent timepoints after the first visit). Comprehensive demographic, clinical, and cognitive batteries were performed in addition to primary investigation of fALFF and ReHo. All pmTBI were classified as "persistent" or "recovered" based on both assessment periods.

Statistical Tests: Chi-square, nonparametric, and generalized linear models for demographic data. Generalized estimating equations for clinical and cognitive data. Voxelwise general linear models (AFNI's 3dMVM) for fALFF and ReHo assessment.

Results: Evidence of recovery was observed for some, but not all, clinical and cognitive measures at 4 months postinjury. fALFF was increased in the left striatum for pmTBI relative to HC both at 1 week and 4 months postinjury; whereas no significant group differences (P > 0.001) were observed for ReHo. Age-at-injury did not moderate either resting-state metric across groups. In contrast to analyses of pmTBI as a whole, there were no significant (P > 0.001) differences in either fALFF or ReHo in patients with persistent postconcussive symptoms compared to recovered patients and controls at 4 months postinjury.

Data Conclusions: Our findings suggest prolonged clinical recovery and alterations in the relative amplitude of resting-state fluctuations up to 4 months postinjury, but no clear relationship with age-at-injury or subjective symptom report.

Level Of Evidence: 1 TECHNICAL EFFICACY: 2 J. MAGN. RESON. IMAGING 2020;52:1701-1713.
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http://dx.doi.org/10.1002/jmri.27249DOI Listing
December 2020

Evidence for asymmetric inhibitory activity during motor planning phases of sensorimotor synchronization.

Cortex 2020 08 15;129:314-328. Epub 2020 May 15.

Department of Neurology, University of New Mexico, Albuquerque, NM, USA.

Sensorimotor synchronization (SMS) is frequently dependent on coordination of excitatory and inhibitory activity across hemispheres, as well as the cognitive control over environmental distractors. However, the timing (motor planning versus execution) and cortical regions involved in these processes remain actively debated. Functional magnetic resonance imaging data were therefore analyzed from 34 strongly right-handed healthy adults performing a cued (to initiate motor planning) SMS task with either their right or left hand (motor execution phase) based on spatially congruent or incongruent visual stimuli. Behavioral effects of incongruent stimuli were limited to the first stimulus. Functionally, greater activation was observed in left sensorimotor cortex (SMC) and right cerebellar Lobule V for congruent versus incongruent stimuli. A negative blood-oxygen level dependent response, a putative marker of neural inhibition, was present in bilateral SMC, right supplemental motor area (SMA) and bilateral cerebellar Lobule V during the motor planning, but not execution phase. The magnitude of the inhibitory response was greater in right cortical regions and cerebellar Lobule V. Homologue connectivity was associated with inhibitory activity in the right SMA, suggesting that individual differences in intrinsic connectivity may mediate transcallosal inhibition. In summary, results suggest increased inhibition (i.e., greater negative BOLD response) within the right relative to left hemisphere, which was released once motor programs were executed. Both task and intrinsic functional connectivity results highlight a critical role of the left SMA in interhemispheric inhibition and motor planning.
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http://dx.doi.org/10.1016/j.cortex.2020.04.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390684PMC
August 2020

ENIGMA brain injury: Framework, challenges, and opportunities.

Hum Brain Mapp 2020 Jun 1. Epub 2020 Jun 1.

Department of Neurology, University of Utah School of Medicine, Salt Lake City, Utah, USA.

Traumatic brain injury (TBI) is a major cause of disability worldwide, but the heterogeneous nature of TBI with respect to injury severity and health comorbidities make patient outcome difficult to predict. Injury severity accounts for only some of this variance, and a wide range of preinjury, injury-related, and postinjury factors may influence outcome, such as sex, socioeconomic status, injury mechanism, and social support. Neuroimaging research in this area has generally been limited by insufficient sample sizes. Additionally, development of reliable biomarkers of mild TBI or repeated subconcussive impacts has been slow, likely due, in part, to subtle effects of injury and the aforementioned variability. The ENIGMA Consortium has established a framework for global collaboration that has resulted in the largest-ever neuroimaging studies of multiple psychiatric and neurological disorders. Here we describe the organization, recent progress, and future goals of the Brain Injury working group.
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http://dx.doi.org/10.1002/hbm.25046DOI Listing
June 2020

Prognosis for Persistent Post Concussion Symptoms using a Multifaceted Objective Gait and Balance Assessment Approach.

Gait Posture 2020 06 20;79:53-59. Epub 2020 Apr 20.

The Micheli Center for Sports Injury Prevention, Waltham, MA, USA; Division of Sports Medicine, Boston Children's Hospital.

Background: Concussion prognosis is a challenging clinical task. Identification of measures useful for persistent symptom risk can help optimize treatment pathways and allow clinicians to offer appropriate anticipatory guidance.

Research Question: Can a multifaceted single/dual-task postural control assessment within one week of a diagnosed concussion identify the odds of developing persistent post-concussion symptoms (PPCS; symptoms that persist for more than 28 days post-concussion)?

Methods: We conducted a prospective cohort study of youth and young adult athletes who were evaluated within 7 days of injury, and followed until they no longer reported concussion symptoms. Participants were grouped into those who developed PPCS and those who did not. During the initial evaluation, participants completed a postural control evaluation in single/dual-task conditions. We calculated six gait performance variables (in single/dual-task conditions), nine quiet stance performance variables, and three cognitive task performance (standing and walking) variables. We conducted between-group comparisons to identify candidate PPCS prognostic variables, and multivariable models to adjust for covariates (age, post-injury evaluation time, history of concussion, and BMI).

Results: Sixty-six participants completed the study: 24% reported PPCS (mean age = 16.9 ± 3.5 years; 50% female; evaluated 4.2 ± 1.9 days post-injury) and 74% (mean age = 18.3 ± 3.0 years; 52% female; evaluated 3.5 ± 1.6 days post-injury) did not. Between-group comparisons indicated greater dual-task transverse plane center-of-mass (COM) range of motion (ROM) (13.1 ± 4.3 vs. 9.9 ± 2.5 degrees; p = 0.013) and lateral step variability (5.1 ± 1.4 vs. 4.0 ± 1.2 cm; p = 0.003) for the PPCS group relative to the no PPCS group. After multivariable modeling, dual-task transverse plane COM ROM (adjusted odds ratio = 1.34, 95% CI = 1.07, 1.68) and lateral step variability (adjusted odds ratio = 1.85, 95% CI = 1.13, 3.05) were significantly associated with PPCS.

Significance: Dual-task transverse plane movement and lateral step variability demonstrate viable prognostic ability for PPCS among youth and young adult athletes and, along with other established factors, may add incremental value to PPCS prognosis models.
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http://dx.doi.org/10.1016/j.gaitpost.2020.04.013DOI Listing
June 2020

Fluid Biomarkers of Pediatric Mild Traumatic Brain Injury: A Systematic Review.

J Neurotrauma 2020 10 2;37(19):2029-2044. Epub 2020 Jun 2.

Departments of Neurosurgery, Cell Biology, Neurobiology and Anatomy, and Biomedical Engineering, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

Public concern is growing about the short- and long-term effects of pediatric mild traumatic brain injury (mTBI). This concern is amplified because pediatric mTBI has the potential to go undiagnosed in acute care settings, placing children at increased risk for reinjury prior to complete recovery. The management of mTBI can be particularly challenging due to the lack of validated biomarkers that clinicians can use to objectively diagnose pediatric mTBI, predict risk for prolonged recovery, or demonstrate mTBI recovery. Fluid-based biomarkers have drawn increased attention as an objective measure to diagnose and manage pediatric mTBI, but investigations of promising biomarkers may pose unique challenges in pediatric populations. Our systematic review confirms the relative paucity of high-quality, clinically impactful diagnostic or prognostic fluid biomarker studies, on samples representing only a small fraction of pediatric mTBI. Ultimately, well-designed longitudinal studies across diverse points of care are needed to truly characterize the utility of fluid biomarkers of injury and recovery for the pediatric mTBI patient.
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http://dx.doi.org/10.1089/neu.2019.6956DOI Listing
October 2020

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.

Transl Psychiatry 2020 03 20;10(1):100. Epub 2020 Mar 20.

Department of Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA, USA.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.
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http://dx.doi.org/10.1038/s41398-020-0705-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083923PMC
March 2020

Medical Cannabis Reduced Agitation in Acquired Brain Injury: A Case Study.

Psychosomatics 2020 Nov - Dec;61(6):819-824. Epub 2020 Feb 25.

Department of Psychiatry and Behavioral Sciences, University of New Mexico Health Sciences Center, Albuquerque, NM.

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http://dx.doi.org/10.1016/j.psym.2020.01.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483629PMC
February 2020

Amygdala response to emotional faces in adolescents with persistent post-concussion symptoms.

Neuroimage Clin 2020 19;26:102217. Epub 2020 Feb 19.

Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, United States. Electronic address:

Approximately 30% of adolescents with concussion develop persistent post-concussion symptoms (PPCS) that include emotional symptoms. Elevated amygdalae reactivity to emotional faces has been reported in a variety of psychopathologies characterized by emotional symptoms overlapping with those in PPCS. We tested the hypothesis that amygdalae reactivity to emotional faces in adolescents with PPCS+ is elevated compared to concussed adolescents without PPCS and healthy controls. Concussed adolescents (ages 14-18) with (PPCS+; n = 23) and without PPCS (PPCS-; n = 13) participated in visits at least 4 weeks post-injury. Adolescents without prior concussion served as controls (HC; n = 15). All participants completed a detailed clinical battery and a common emotional face processing task that involved matching of emotional faces or shapes. Compared to HC and PPCS-, adolescents with PPCS+ had elevated depression symptoms, anhedonia, general psychological symptoms, and anxiety symptoms. Contrary to our hypothesis, PPCS+ had lower amygdalae activity to the emotional faces versus shapes condition relative to HC and a trend for lower activity relative to PPCS-. There was a non-significant inverse association between anhedonia amygdalae activity in adolescents with PPCS. Results suggest that adolescents with PPCS have altered amygdalae activity during the processing of emotional face stimuli.
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http://dx.doi.org/10.1016/j.nicl.2020.102217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044530PMC
February 2021

Neurosensory Screening and Symptom Provocation in Pediatric Mild Traumatic Brain Injury.

J Head Trauma Rehabil 2020 Jul/Aug;35(4):270-278

The Mind Research Network/Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico (Drs Mayer, Stephenson, Hanlon, and Phillips, Messrs Wertz, Dodd, and Shaff, and Mss Robertson-Benta and Pabbathi Reddy); Departments of Psychiatry and Behavioral Sciences (Dr Mayer), Psychology (Drs Mayer and Campbell), Neurology (Drs Mayer and Phillips), and Emergency Medicine (Mr Oglesbee and Dr Park), University of New Mexico, Albuquerque; Department of Epidemiology and Biostatistics, University of Arizona, Tucson (Dr Bedrick); Center for Injury Research and Prevention, Department of Pediatrics (Drs Master, Grady, and Arbogast), and Division of Orthopedic Surgery (Drs Master and Grady), The Children's Hospital of Philadelphia, Philadelphia; Department of Pediatrics and Emergency Medicine, Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada (Dr Zemek); Department of Psychology (Dr Yeates), Alberta Children's Hospital Research Institute (Dr Yeates), and Hotchkiss Brain Institute (Dr Yeates), University of Calgary, Calgary, Alberta, Canada; Department of Neurosurgery, Medical College of Wisconsin, Milwaukee (Dr Meier); Departments of Cell Biology, Neurobiology and Anatomy (Dr Meier) and Biomedical Engineering (Dr Meier), Medical College of Wisconsin, Milwaukee; Division of Emergency Medicine, Boston Children's Hospital, Boston, Massachusetts (Dr Mannix); and UBMD Department of Orthopaedics and Sports Medicine, Jacobs School of Medicine, University at Buffalo, Buffalo, New York (Dr Leddy).

Objective: To evaluate diagnostic/prognostic implications of neurosensory testing during the subacute stage in patients with pediatric mild traumatic brain injury (pmTBI).

Setting: Recruitment from pediatric emergency department and urgent care clinics, assessment in a controlled environment.

Participants: In total, 146 pmTBI patients evaluated 7.4 ± 2.3 days and approximately 4 months postinjury; 104 age/sex-matched healthy controls (HCs) at equivalent time points.

Design: Prospective cohort study.

Main Measures: Neurosensory examination based on sequence of 10 established tests of vestibular-ocular, oculomotor, vestibulospinal, and visual functioning.

Results: The amount of symptom provocation (positive change from pretest symptomatology) was significantly increased in pmTBI relative to HCs on every subtest 1 week postinjury, as were deficits in monocular accommodative amplitude and King-Devick Test errors. However, symptom provocation did not meaningfully alter diagnostic sensitivity/specificity relative to more easily obtained pretest symptom ratings. Evidence of clinically significant symptom provocation 1 week postinjury improved sensitivity (Δ = +12.9%) of identifying patients with persistent postconcussive symptoms 4 months postinjury on an independent symptom measure.

Conclusions: The diagnostic sensitivity/specificity of neurosensory testing in acutely concussed youth may be limited at 1 week postinjury as a function of natural recovery occurring in most emergency department cohorts. Neurosensory screening may have greater utility for identifying patients who experience delayed recovery.
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http://dx.doi.org/10.1097/HTR.0000000000000560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335318PMC
September 2021
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