Faculty Bibliography

Unprecedented media coverage of concussion in sport has led to increased fears regarding the potential negative effects of participation in contact sports including North American football and ice hockey. Initial responses of professional sports leagues to implementation of acute concussion management practices and reports of a neurodegenerative condition known as chronic traumatic encephalopathy (CTE) developing in retired players caused an atmosphere of distrust whereby the leagues were accused of maintaining cover-ups analogous to what had been seen in association with studies of tobacco and smoking. This article reviews the important role that psychology has played in the study of sports concussion and in the establishment of methods currently used to diagnose and track concussion symptoms. Results of existing studies have shown that the neurobiological effects of concussion are rather short-lived with development of persisting symptoms in some individuals associated more with psychosocial factors than underlying physiological effects. With regard to CTE, the status of the science remains preliminary with little definitive information known about its epidemiology or cause. In the midst of the ongoing controversy, a polarized climate has developed in association with concussion and CTE, divided by believers in the dangers of long-term consequences and deniers who question the status of the existing science. The conclusion is that it is important for psychology to extend its scope of study to provide increased understanding of the social factors underlying the current polarized climate while continuing to provide the public with an accurate and reliable account of the existing science. (PsycInfo Database Record (c) 2020 APA, all rights reserved)Public Significance Statement"”Continued media reporting of the sports concussion and its potential long-term effects has been accompanied by public concerns about the safety of contact sports and potential development of chronic traumatic encephalopathy (CTE). Controversies have emerged about the status of the science, creating polarization on the topic. Psychology has provided significant contributions to our scientific knowledge on sports concussion and has the potential to provide a key to understanding the factors underlying division on these topics. (PsycInfo Database Record (c) 2020 APA, all rights reserved)Une couverture médiatique sans précédent des commotions cérébrales dans le sport a entraîné une augmentation des craintes quant aux effets négatifs potentiels de la participation aux sports de contact, notamment au football et au hockey sur glace en Amérique du Nord. Les premières réponses des ligues sportives professionnelles à la mise en Å“uvre de pratiques de gestion des commotions aiguës et les déclarations de maladie neurodégénérative connue sous le nom d"™encéphalopathie traumatique chronique (CTE) en développement chez les joueurs retraités ont provoqué une atmosphère de méfiance où les ligues ont été accusées de dissimulations de manière similaire à ce qui avait été observé avec les études sur le tabac et le tabagisme. Le présent article examine le rôle important que la psychologie a joué dans l"™Ã©tude des commotions liées au sport et dans l"™Ã©tablissement de méthodes actuellement utilisées pour diagnostiquer et surveiller les symptômes de commotion cérébrale. Les résultats des études existantes ont montré que les effets neurobiologiques de commotion cérébrale sont plutôt de courte durée avec l"™apparition de symptômes persistants, chez certaines personnes, plutôt associés à des facteurs psychosociaux qu"™aux effets physiologiques sous-jacents. En ce qui concerne la CTE, le statut de la science reste préliminaire, avec peu de renseignements définitifs connus sur son épidémiologie ou sa cause. Au cÅ“ur de la controverse actuelle, un climat polarisé s"™est développé en lien avec la commotion cérébrale et la CTE, divisé par les croyants aux dangers des conséquences à long terme et les négateurs qui remettent en question le statut de la science existante. En conclusion, il est important pour la psychologie d"™Ã©tendre sa portée d"™Ã©tude afin de mieux comprendre les facteurs sociaux sous-jacents au climat polarisé actuel tout en continuant à fournir au public un compte rendu exact et fiable de la science existante. (PsycInfo Database Record (c) 2020 APA, all rights reserved)

Studies of sensorimotor integration often use sensory stimuli that require a simple motor response, such as a reach or a grasp. Recent advances in neural recording techniques, motion capture technologies, and time-synchronization methods enable studying sensorimotor integration using more complex sensory stimuli and performed actions. Here, we demonstrate that prehensile actions that require using complex sensory instructions for manipulating different objects can be characterized using high-density electroencephalography and motion capture systems. In 20 participants, we presented stimuli in different sensory modalities (visual, auditory) containing different contextual information about the object with which to interact. Neural signals recorded near motor cortex and posterior parietal cortex discharged based on both the instruction delivered and object manipulated. Additionally, kinematics of the wrist movements could be discriminated between participants. These findings demonstrate a proof-of-concept behavioral paradigm for studying sensorimotor integration of multidimensional sensory stimuli to perform complex movements. Such a framework will prove vital for studying neural control of movements in clinical populations in which sensorimotor integration is impaired due to information no longer being communicated correctly between brain regions (e.g. stroke). Such a framework is the first step towards developing a neural rehabilitative system for restoring function more effectively.

OBJECTIVE:To assay EEG signal quality recorded with tripolar concentric ring electrodes (TCREs) compared to regular EEG electrodes. METHODS:EEG segments were recorded simultaneously by TCREs and regular electrodes, low-pass filtered at 35 Hz (REG35) and 70 Hz (REG70). Clips were rated blindly by nine electroencephalographers for presence or absence of key EEG features, relative to the "gold-standard" of the clinical report. RESULTS:TCRE showed less EMG artifact (F = 15.4, p < 0.0001). Overall quality rankings were not significantly different. Focal slowing was better detected by TCRE and spikes were better detected by regular electrodes. Seizures (n = 85) were detected by TCRE in 64 cases (75.3%), by REG70 in 75 (88.2%) and REG35 in 69 (81.2%) electrodes. TCRE detected 9 (10.6%) seizures not detected by one of the other 2 methods. In contrast, 14 seizures (16.5%) were not detected by TCRE, but were by REG35 electrodes. Each electrode detected interictal spikes when the other did not. CONCLUSIONS:TCRE produced similar overall quality and confidence ratings versus regular electrodes, but less muscle artifact. TCRE recordings detected seizures in 7% of instances where regular electrodes did not. SIGNIFICANCE/CONCLUSIONS:The combination of the two types increased detection of epileptiform events compared to either alone.

Background/UNASSIGNED:Glioma is a family of primary brain malignancies with limited treatment options and in need of novel therapies. We previously demonstrated that the adhesion G protein-coupled receptor GPR133 (ADGRD1) is necessary for tumor growth in adult glioblastoma, the most advanced malignancy within the glioma family. However, the expression pattern of GPR133 in other types of adult glioma is unknown. Methods/UNASSIGNED:We used immunohistochemistry in tumor specimens and non-neoplastic cadaveric brain tissue to profile GPR133 expression in adult gliomas. Results/UNASSIGNED:We show that GPR133 expression increases as a function of WHO grade and peaks in glioblastoma, where all tumors ubiquitously express it. Importantly, GPR133 is expressed within the tumor bulk, as well as in the brain-infiltrating tumor margin. Furthermore, GPR133 is expressed in both isocitrate dehydrogenase (IDH) wild-type and mutant gliomas, albeit at higher levels in IDH wild-type tumors. Conclusion/UNASSIGNED:The fact that GPR133 is absent from non-neoplastic brain tissue but de novo expressed in glioma suggests that it may be exploited therapeutically.

OBJECTIVE:Generalized epileptiform discharges (GEDs) can occur during seizures or without obvious clinical accompaniment. Motor vehicle driving risk during apparently subclinical GEDs is uncertain. Our goals were to develop a feasible, realistic test to evaluate driving safety during GEDs, and to begin evaluating electroencephalographic (EEG) features in relation to driving safety. METHODS:Subjects were aged ≥15 years with generalized epilepsy, GEDs on EEG, and no clinical seizures. Using a high-fidelity driving simulator (miniSim) with simultaneous EEG, a red oval visual stimulus was presented every 5 minutes for baseline testing, and with each GED. Participants were instructed to pull over as quickly and safely as possible with each stimulus. We analyzed driving and EEG signals during GEDs. RESULTS:Nine subjects were tested, and five experienced 88 GEDs total with mean duration 2.31 ± 1.89 (SD) seconds. Of these five subjects, three responded appropriately to all stimuli, one failed to respond to 75% of stimuli, and one stopped driving immediately during GEDs. GEDs with no response to stimuli were significantly longer than those with appropriate responses (8.47 ± 3.10 vs 1.85 ± 0.69 seconds, P < .001). Reaction times to stimuli during GEDs were significantly correlated with GED duration (r = 0.30, P = .04). In addition, EEG amplitude was greater for GEDs with no response to stimuli than GEDs with responses, both for overall root mean square voltage amplitude (66.14 μV vs 52.99 μV, P = .02) and for fractional power changes in the frequency range of waves (P < .05) and spikes (P < .001). SIGNIFICANCE:High-fidelity driving simulation is feasible for investigating driving behavior during GEDs. GEDs with longer duration and greater EEG amplitude showed more driving impairment. Future work with a large sample size may ultimately enable classification of GED EEG features to predict individual driving risk.

BACKGROUND AND PURPOSE/OBJECTIVE:In this study, we used power analysis to calculate required sample sizes to detect group-level changes in quantitative neuroanatomical estimates derived from MRI scans obtained from multiple imaging centers. Sample size estimates were derived from (i) standardized 3T image acquisition protocols and (ii) nonstandardized clinically acquired images obtained at both 1.5 and 3T as part of the multicenter Human Epilepsy Project. Sample size estimates were compared to assess the benefit of standardizing acquisition protocols. METHODS:Cortical thickness, hippocampal volume, and whole brain volume were estimated from whole brain T1-weighted MRI scans processed using Freesurfer v6.0. Sample sizes required to detect a range of effect sizes were calculated using (i) standard t-test based power analysis methods and (ii) a nonparametric bootstrap approach. RESULTS:A total of 32 participants were included in our analyses, aged 29.9 ± 12.62 years. Standard deviation estimates were lower for all quantitative neuroanatomical metrics when assessed using standardized protocols. Required sample sizes per group to detect a given effect size were markedly reduced when using standardized protocols, particularly for cortical thickness changes <.2 mm and hippocampal volume changes <10%. CONCLUSIONS:The use of standardized protocols yielded up to a five-fold reduction in required sample sizes to detect disease-related neuroanatomical changes, and is particularly beneficial for detecting subtle effects. Standardizing image acquisition protocols across scanners prior to commencing a study is a valuable approach to increase the statistical power of multicenter MRI studies.

OBJECTIVES/OBJECTIVE:This study aims to investigate the role and mechanism of FGFR3 in macrophages and their biological effects on the pathology of arthritis. METHODS:Mice with conditional knockout of FGFR3 in myeloid cells (R3cKO) were generated. Gait behaviours of the mice were monitored at different ages. Spontaneous synovial joint destruction was evaluated by digital radiographic imaging and μCT analysis; changes of articular cartilage and synovitis were determined by histological analysis. The recruitment of macrophages in the synovium was examined by immunostaining and monocyte trafficking assay. RNA-seq analysis, Western blotting and chemotaxis experiment were performed on control and FGFR3-deficient macrophages. The peripheral blood from non-osteoarthritis (OA) donors and patients with OA were analysed. Mice were treated with neutralising antibody against CXCR7 to investigate the role of CXCR7 in arthritis. RESULTS:R3cKO mice but not control mice developed spontaneous cartilage destruction in multiple synovial joints at the age of 13 months. Moreover, the synovitis and macrophage accumulation were observed in the joints of 9-month-old R3cKO mice when the articular cartilage was not grossly destructed. FGFR3 deficiency in myeloid cells also aggravated joint destruction in DMM mouse model. Mechanically, FGFR3 deficiency promoted macrophage chemotaxis partly through activation of NF-κB/CXCR7 pathway. Inhibition of CXCR7 could significantly reverse FGFR3-deficiency-enhanced macrophage chemotaxis and the arthritic phenotype in R3cKO mice. CONCLUSIONS:Our study identifies the role of FGFR3 in synovial macrophage recruitment and synovitis, which provides a new insight into the pathological mechanisms of inflammation-related arthritis.