Publications by authors named "Andrew Mayer"

186 Publications

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

J Neurotrauma 2021 Mar 31. Epub 2021 Mar 31.

University of New Mexico Health Sciences Center, 12289, Psychiatry and Behavioral Sciences, 1101 Yale Boulevard NE, Pete and Nancy Domenici Hall, Albuquerque, New Mexico, United States, 87106;

Apathy is a common and impairing sequela of traumatic brain injury (TBI). Yet, little is known about the neural mechanisms determining which patients do or do not develop apathy post-TBI. Here 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 (rsfMRI) data were collected in patients with subacute mild TBI (N=44), chronic mild-to-moderate TBI (N=26), and non-brain-injured control participants (CTRL; N=28). We measured ventromedial prefrontal cortex (vmPFC) functional connectivity (FC) as a function of apathy, using an a priori 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. 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 prior work suggesting that apathy has an enduring impact in TBI. 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. Lastly, 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 represents 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/neu.2020.7363DOI Listing
March 2021

The importance of quality critical reagents for the entire developmental lifecycle of a biopharmaceutical: a pharmacokinetic case study.

Bioanalysis 2021 Mar 26. Epub 2021 Mar 26.

Bioanalysis, Immunogenicity & Biomarkers, In-Vitro/In-Vivo Translation, R&D Research, GlaxoSmithKline Pharmaceuticals, 1250 South Collegeville Rd, Collegeville, PA 19426, USA.

High-quality critical reagents are essential to the successful support of biotherapeutic drug development regardless of the analytical platform used for support. The lack of such a reagent, early in the development lifecycle of a biotherapeutic can have detrimental impact on resource and translation of data across development phases. Here, a pharmacokinetic assay case study is shared that illustrates what can occur when there is a lack of a reproducible and sustainable critical reagent early in the development lifecycle of a biotherapeutic. Various assay formats and critical reagents, as well as reagents generation programs, were initiated to find a reagent and assay format which was fit for purpose. Identification of appropriate critical reagents early in the development lifecycle of a biotherapeutic as advantageous.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4155/bio-2020-0253DOI Listing
March 2021

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

Schizophr Res 2021 Feb 16;229:12-21. Epub 2021 Feb 16.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.schres.2021.01.016DOI Listing
February 2021

The effectiveness of quality control samples in pharmaceutical bioanalysis.

Bioanalysis 2021 Feb 4;13(3):135-145. Epub 2021 Feb 4.

Bristol-Myers Squibb Co. Princeton, NJ 08540, USA.

The use of quality control (QC) samples in bioanalysis is well established and consistent with regulatory guidance. However, a systematic evaluation of whether QC samples serve the intended purpose of improving data quality has not been undertaken. The Translational and ADME Sciences Leadership Group (TALG) of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) conducted an evaluation to assess whether closer agreement is observed when comparing pharmacokinetic data from two passed runs, than when comparing data from failed and passed (retest) runs. Analysis of data collected across organizations, molecular types and analytical platforms, revealed that bioanalytical methods are very reproducible; and that QC samples improve the overall quality of pharmacokinetic concentration data and justifies their continued use.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4155/bio-2020-0265DOI Listing
February 2021

2020 White Paper on Recent Issues in Bioanalysis: BAV Guidance, CLSI H62, Biotherapeutics Stability, Parallelism Testing, CyTOF and Regulatory Feedback ( - Recommendations on Biotherapeutics Stability, PK LBA Regulated Bioanalysis, Biomarkers Assays, Cytometry Validation & Innovation - Regulatory Agencies' Inputs on Bioanalysis, Biomarkers, Immunogenicity, Gene & Cell Therapy and Vaccine).

Bioanalysis 2021 Mar 29;13(5):295-361. Epub 2021 Jan 29.

Health Canada, Ottawa, ON, Canada.

The 14 edition of the Workshop on Recent Issues in Bioanalysis (14 WRIB) was held virtually on June 15-29, 2020 with an attendance of over 1000 representatives from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations, and regulatory agencies worldwide. The 14 WRIB included three Main Workshops, seven Specialized Workshops that together spanned 11 days in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy and vaccine. Moreover, a comprehensive vaccine assays track; an enhanced cytometry track and updated Industry/Regulators consensus on BMV of biotherapeutics by LCMS were special features in 2020. As in previous years, this year's WRIB continued to gather a wide diversity of international industry opinion leaders and regulatory authority experts working on both small and large molecules to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance and achieving scientific excellence on bioanalytical issues. This 2020 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the Global Bioanalytical Community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2020 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication covers the recommendations on (Part 2A) BAV, PK LBA, Flow Cytometry Validation and Cytometry Innovation and (Part 2B) Regulatory Input. Part 1 (Innovation in Small Molecules, Hybrid LBA/LCMS & Regulated Bioanalysis), Part 3 (Vaccine, Gene/Cell Therapy, NAb Harmonization and Immunogenicity) are published in volume 13 of Bioanalysis, issues 4, and 6 (2021), respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4155/bio-2021-0005DOI Listing
March 2021

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

Brain Inj 2021 Jan 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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 Feb 16. 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/neu.2020.7143DOI Listing
February 2021

Use of Medical Cannabis to Treat Traumatic Brain Injury.

J Neurotrauma 2021 Jan 25. 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/neu.2020.7148DOI Listing
January 2021

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

J Int Neuropsychol Soc 2020 Nov 27:1-11. 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1355617720001228DOI Listing
November 2020

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

Am J Obstet Gynecol 2020 Oct 26. 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajog.2020.10.041DOI Listing
October 2020

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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 Apr;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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SHK.0000000000001653DOI Listing
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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

Western University of Health Sciences, Pomona, CA, 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hbm.25046DOI Listing
June 2020

Antibody Subunit LC-MS Analysis for Pharmacokinetic and Biotransformation Determination from In-Life Studies for Complex Biotherapeutics.

Anal Chem 2020 06 22;92(12):8268-8277. Epub 2020 May 22.

Complex biotherapeutics present challenges from drug discovery, screening, and development perspectives. While monoclonal antibody drugs are not monitored for metabolites in the same manner as small molecules, biotherapeutics such as fusion proteins, antibody-drug conjugates, or bispecific antibodies may undergo biotransformation (such as clipping, deamidation, or oxidation) in vivo, resulting in catabolites that can have a direct impact on drug safety or efficacy. Here antibody subunit LC-MS is utilized for evaluation of two classes of complex biotherapeutics: an antibody-drug conjugate and a mAb-fusion biotherapeutic. Pharmacokinetic concentration, biotransformation, and DAR data are collectively presented using the subunit LC-MS approach for the two molecules, and the methods shared in detail can be applied to any humanized IgG1 mAb biotherapeutic for preclinical study support. Overall, the data generated from antibody LC-MS analyses can provide key information in early phase development and deliver multiple study end points with a single data set.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.analchem.0c00520DOI 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.

Authors:
Paul M Thompson Neda Jahanshad Christopher R K Ching Lauren E Salminen Sophia I Thomopoulos Joanna Bright Bernhard T Baune Sara Bertolín Janita Bralten Willem B Bruin Robin Bülow Jian Chen Yann Chye Udo Dannlowski Carolien G F de Kovel Gary Donohoe Lisa T Eyler Stephen V Faraone Pauline Favre Courtney A Filippi Thomas Frodl Daniel Garijo Yolanda Gil Hans J Grabe Katrina L Grasby Tomas Hajek Laura K M Han Sean N Hatton Kevin Hilbert Tiffany C Ho Laurena Holleran Georg Homuth Norbert Hosten Josselin Houenou Iliyan Ivanov Tianye Jia Sinead Kelly Marieke Klein Jun Soo Kwon Max A Laansma Jeanne Leerssen Ulrike Lueken Abraham Nunes Joseph O' Neill Nils Opel Fabrizio Piras Federica Piras Merel C Postema Elena Pozzi Natalia Shatokhina Carles Soriano-Mas Gianfranco Spalletta Daqiang Sun Alexander Teumer Amanda K Tilot Leonardo Tozzi Celia van der Merwe Eus J W Van Someren Guido A van Wingen Henry Völzke Esther Walton Lei Wang Anderson M Winkler Katharina Wittfeld Margaret J Wright Je-Yeon Yun Guohao Zhang Yanli Zhang-James Bhim M Adhikari Ingrid Agartz Moji Aghajani André Aleman Robert R Althoff Andre Altmann Ole A Andreassen David A Baron Brenda L Bartnik-Olson Janna Marie Bas-Hoogendam Arielle R Baskin-Sommers Carrie E Bearden Laura A Berner Premika S W Boedhoe Rachel M Brouwer Jan K Buitelaar Karen Caeyenberghs Charlotte A M Cecil Ronald A Cohen James H Cole Patricia J Conrod Stephane A De Brito Sonja M C de Zwarte Emily L Dennis Sylvane Desrivieres Danai Dima Stefan Ehrlich Carrie Esopenko Graeme Fairchild Simon E Fisher Jean-Paul Fouche Clyde Francks Sophia Frangou Barbara Franke Hugh P Garavan David C Glahn Nynke A Groenewold Tiril P Gurholt Boris A Gutman Tim Hahn Ian H Harding Dennis Hernaus Derrek P Hibar Frank G Hillary Martine Hoogman Hilleke E Hulshoff Pol Maria Jalbrzikowski George A Karkashadze Eduard T Klapwijk Rebecca C Knickmeyer Peter Kochunov Inga K Koerte Xiang-Zhen Kong Sook-Lei Liew Alexander P Lin Mark W Logue Eileen Luders Fabio Macciardi Scott Mackey Andrew R Mayer Carrie R McDonald Agnes B McMahon Sarah E Medland Gemma Modinos Rajendra A Morey Sven C Mueller Pratik Mukherjee Leyla Namazova-Baranova Talia M Nir Alexander Olsen Peristera Paschou Daniel S Pine Fabrizio Pizzagalli Miguel E Rentería Jonathan D Rohrer Philipp G Sämann Lianne Schmaal Gunter Schumann Mark S Shiroishi Sanjay M Sisodiya Dirk J A Smit Ida E Sønderby Dan J Stein Jason L Stein Masoud Tahmasian David F Tate Jessica A Turner Odile A van den Heuvel Nic J A van der Wee Ysbrand D van der Werf Theo G M van Erp Neeltje E M van Haren Daan van Rooij Laura S van Velzen Ilya M Veer Dick J Veltman Julio E Villalon-Reina Henrik Walter Christopher D Whelan Elisabeth A Wilde Mojtaba Zarei Vladimir Zelman

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

Keck School of Medicine, University of Southern California, Los Angeles, 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.

View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/HTR.0000000000000560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335318PMC
July 2021

Brain activation and subjective anxiety during an anticipatory anxiety task is related to clinical outcome during prazosin treatment for alcohol use disorder.

Neuroimage Clin 2020 10;26:102162. Epub 2020 Jan 10.

Department of Psychiatry, New York University School of Medicine, New York, NY 10016, USA.

Background: Higher levels of anxiety, negative affect, and impaired emotion regulation are associated with alcohol use disorder (AUD) and contribute to relapse and worse treatment outcomes. Prazosin, while typically used to treat post-traumatic stress disorder (PTSD) and other anxiety disorders, has shown promise for treating AUD. In order to better understand these underlying neural processes in individuals with AUD, our aims in this study were to measure brain activation during an anticipatory anxiety task before treatment to determine whether observed patterns supported previous work. We then aimed to measure the effects of prazosin on patients with AUD and explore whether greater baseline anticipatory anxiety (as measured by subjective and neural measures) predicts better treatment outcomes.

Methods: Thirty-four individuals seeking treatment for AUD participated in a six-week placebo-controlled study of prazosin and underwent an anticipatory anxiety task during fMRI scans at baseline and three weeks. Alcohol use over six weeks was measured.

Results: Greater levels of subjective anxiety and deactivation in posterior cingulate cortex (PCC) and ventromedial prefrontal cortex (vmPFC) were observed during high-threat stimuli compared to low-threat stimuli. Compared to placebo, prazosin reduced subjective anxiety to high-threat stimuli but there were no observed significant effects of prazosin on brain activation during the task. However, AUD patients with greater vmPFC deactivation during high threat relative to low threat and patients with low baseline anticipatory anxiety during the task had worse clinical outcomes on prazosin.

Conclusions: Deactivation in PCC and vmPFC to high-threat stimuli replicated previous work and shows promise for further study as a marker for AUD. Although prazosin did not affect brain activation in the regions of interest during the anticipatory anxiety task, subjective levels of anxiety and brain activation in vmPFC predicted treatment outcomes in individuals with AUD undergoing treatment with prazosin, highlighting individuals more likely to benefit from prazosin than others.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nicl.2020.102162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229347PMC
February 2021

Comparison of Methods for Classifying Persistent Post-Concussive Symptoms in Children.

J Neurotrauma 2020 07 12;37(13):1504-1511. Epub 2020 Mar 12.

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

Pediatric mild traumatic brain injury (pmTBI) has received increased public scrutiny over the past decade, especially regarding children who experience persistent post-concussive symptoms (PPCS). However, several methods for defining PPCS exist in clinical and scientific literature, and even healthy children frequently exhibit non-specific, concussive-like symptoms. Inter-method agreement (six PPCS methods), observed misclassification rates, and other psychometric properties were examined in large cohorts of consecutively recruited adolescent patients with pmTBI ( = 162) 1 week and 4 months post-injury and in age/sex-matched healthy controls (HC;  = 117) at equivalent time intervals. Six published PPCS methods were stratified into Simple Change (e.g., , 10th revision [ICD-10]) and Standardized Change (e.g., reliable change indices) algorithms. Among HC, test-retest reliability was fair to good across the 4-month assessment window, with evidence of bias (i.e., higher symptom ratings) during retrospective relative to other assessments. Misclassification rates among HC were higher (>30%) for Simple Change algorithms, with poor inter-rater reliability of symptom burden across HC and their parents. A 49% spread existed in terms of the proportion of pmTBI patients "diagnosed" with PPCS at 4 months, with superior inter-method agreement among standardized change algorithms. In conclusion, the self-reporting of symptom burden is only modestly reliable in typically developing adolescents over a 4-month period, with additional evidence for systematic bias in both adolescent and parental ratings. Significant variation existed for identifying pmTBI patients who had "recovered" (i.e., those who did not meet individual criteria for PPCS) from concussion across the six definitions, representing a considerable challenge for estimating the true incidence rate of PPCS in published literature. Although relatively straightforward to obtain, current findings question the utility of the most commonly used Simple Change scores for diagnosis of PPCS in clinical settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/neu.2019.6805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307699PMC
July 2020

Persistent alterations in cerebrovascular reactivity in response to hypercapnia following pediatric mild traumatic brain injury.

J Cereb Blood Flow Metab 2020 12 5;40(12):2491-2504. Epub 2020 Jan 5.

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

Much attention has been paid to the effects of mild traumatic brain injury (mTBI) on cerebrovascular reactivity in adult populations, yet it remains understudied in pediatric injury. In this study, 30 adolescents (12-18 years old) with pediatric mTBI (pmTBI) and 35 age- and sex-matched healthy controls (HC) underwent clinical and neuroimaging assessments during sub-acute (6.9 ± 2.2 days) and early chronic (120.4 ± 11.7 days) phases of injury. Relative to controls, pmTBI reported greater initial post-concussion symptoms, headache, pain, and anxiety, resolving by four months post-injury. Patients reported increased sleep issues and exhibited deficits in processing speed and attention across both visits. In grey-white matter interface areas throughout the brain, pmTBI displayed increased maximal fit/amplitude of a time-shifted end-tidal CO regressor to blood oxygen-level dependent response relative to HC, as well as increased latency to maximal fit. The alterations persisted through the early chronic phase of injury, with maximal fit being associated with complaints of ongoing sleep disturbances during post hoc analyses but not cognitive measures of processing speed or attention. Collectively, these findings suggest that deficits in the speed and degree of cerebrovascular reactivity may persist longer than current conceptualizations about clinical recovery within 30 days.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0271678X19896883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820694PMC
December 2020