The Effect of Dual-Tasking on Information Processing in Contact Sport Athletes: Examining the long-term effects of Self-reported Concussion

Objective: Concussions have been linked to deficits in executive functions including, memory and attention, and oculomotor dysfunction, all of which are required to play safely and successfully at an elite level. The goal of the current research was to understand the information processing abilities of varsity hockey athletes in attempts to determine the long-term effects of concussions. Additionally, our research compared clinical and experimental neurocognitive tests for discriminating athletes with and without a history of concussion who have returned-to-play. Since hockey players need excellent memory, attention, and executive function skills, a novel dual-task paradigm was developed by incorporating tasks that require visuospatial working memory and auditory processing. Method: Participants were 29 varsity collegiate ice hockey players (15 females, mean age= 19.1 +1.26, 14 males, mean age= 22.7 + 1.3). Eighteen athletes were diagnosed with a history of concussion based on self-report questionnaires, health history questionnaires, and prior physician diagnosis. The number of concussions were reported as follows: one (n = 9), two (n = 7), and three (n = 2). Participants performed a dual-task involving visuospatial working memory (Corsi block test) and auditory tone discrimination. Each task was presented individually (Vis-Single, Aud-Single), then simultaneously (VisAud-Dual). Eye movements were recorded using the Eyelink II eyetracker during the experimental tests. Also, participants completed a clinical neurocognitive test for concussions called the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT). The main outcome measures were the Corsi block memory span and auditory tone discrimination accuracy. Four ImPACT composite outcome variables were measured including, Verbal Memory, Visual Memory, Visuomotor Processing Speed, and Reaction Time. Finally, the four oculomotor outcome variables measured were rate of task-relevant saccades, microsaccades, and other saccades, and saccade gain. Statistical analyses were completed using 2 and 3-way mixed ANOVA’s, and logistic regressions. The independent factors were two within-subject variables, Task Condition (single, dual), and Difficulty Level (# of targets to remember ranging from 3 to 7) and the between-subject variable was Concussion History (concussion, no concussion). Results: A 2-way mixed ANOVA on tone discrimination accuracy showed athletes with a history of concussion performed significantly worse on the tone discrimination task in the dual-task condition compared to the non-concussion athletes. No significant differences were shown when each task was performed alone, or on the Corsi block test in the dual-task condition. Two separate logistic regression models using ImPACT composites and dual-task measures identified auditory cost as the only significant predictor for Concussion History. Additionally, the dual-task test was more sensitive for discriminating athletes with and without a history of concussion compared to the ImPACT. A 3-way mixed model ANOVA on task-relevant saccades, microsaccades, and other saccades showed no significant differences between athletes with and without a history of concussion. However, a medium effect size was found for task-relevant saccades, which showed that athletes with a history of concussion had a higher rate of saccades. Additional analysis examining saccade gain for both horizontal and vertical saccades showed no significant difference between concussion history groups; however, a medium effect size was found which showed that athletes with a history of concussion had a higher saccade gain. Conclusions: Athletes with a history of concussion may have persistent deficits in executive functions. These deficits were only evident in previously concussed athletes when cognitive resources were stressed during the dual-task condition. In comparison to current clinical neurocognitive tests designed for concussions (i.e., ImPACT), tests examining executive functions appear to be more sensitive for discriminating athletes with and without a history of concussion, thus, should be included in current evaluation protocols. Finally, there were no statistically significant differences in gaze strategies; however, with the addition of more participants, gaze strategies may provide useful information into how athletes with and without a history of concussion encode visuospatial information. Therefore, further evaluation into encoding strategies may be helpful for developing training protocols for a safe return-to-play

Examining behavioural and electrophysiological markers of mental workload in individuals with and without a history of concussion

Objectives: The goal of this thesis was to examine the neurocognitive mechanisms of mental workload for the purpose of improving our knowledge of the long-term effects of concussion. Four experiments were performed manipulating mental workload in individuals with and without a history of concussion. Studies one and two increased mental workload by manipulating set size (i.e., number of items to be remembered) and task condition (single-task, dual-task) in individuals with and without a history of concussion, respectively. In addition, event-related potentials (ERPs) were recorded to examine the neural correlates of information processing that are affected by mental workload. Study three examined mental workload by changing the requirements of the task through the manipulation of pattern configuration characteristics. The fourth study examined mental workload in individuals with and without a history of concussion using three types of workload manipulation: set size, task condition, and pattern configuration complexity. Methods: Thirty-six participants (20 no-concussion, 16 asymptomatic) were recruited for studies one and two, and assessed using a dual-task paradigm involving a computerised eCorsi block task and auditory oddball task that progressively increased in workload (i.e., set size, task condition). ERPs were used to study the sensory and cognitive stages of information processing as a function of mental workload. Seventeen participants (14 no-concussion, 3 asymptomatic) were tested in study three using a computer and phone version of the eCorsi task, which manipulated workload by changing the average angle of a patterns at set sizes of five to eight blocks. Study four examined secondary auditory oddball performance as a function of eCorsi pattern complexity in nineteen participants (9 no-concussion, 10 asymptomatic). Results: The no concussion group showed reduced eCorsi recall accuracy as set size increased, which was maintained between task conditions (single, dual). In contrast, auditory oddball performance decreased (i.e., poorer accuracy, longer response times [RTs]) as mental workload increased (task, set size). ERP’s showed amplitude reductions in early sensory (P50) and later cognitive (P300) potentials when both tasks were performed simultaneously compared to alone. In contrast, later sensory (N100) ERP increased in amplitude. Sensory gating was consistent at both P50 and N100 potentials as a function of mental workload. The concussion history group showed poorer auditory (lower accuracy, more errors of commission, and longer RTs) when both tasks were performed simultaneously whereas no between-group differences were found on the eCorsi task. ERPs indicated poorer sensory gating (P50, N100) and cognitive processing (i.e., reduced P300 amplitude) in the asymptomatic group, which changed as a function of workload. Investigating the properties of the dual-task showed reduced eCorsi recall accuracy in hard patterns (smaller angles, more crosses, and longer distances) compared to easy patterns; however, this did not affect auditory oddball measures. Conclusions: Sensory and cognitive processes change as a function of mental workload (task, set size) and in those with a history of concussion suggesting these individuals have problems gating in important information, which may affect the efficiency of later cognitive processes and subsequent behavioural performance. Importantly, mental workload can be increased by task condition (single, dual), set size (# of items to remember), and path configuration difficulty (easy, hard), which reflect different types of load. These findings are particularly useful in the development of sensitive neurocognitive tests for identifying persisting deficits in individuals with a history of concussion

Saccade latency delays in young apolipoprotein E (APOE) epsilon 4 carriers

The final publication is available at Elsevier via https://dx.doi.org/10.1016/j.bbr.2018.07.002 © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/The apolipoprotein E (APOE) epsilon 4 isoform has been associated with a significantly greater risk of developing late onset Alzheimer’s disease (AD). However, the negative effects of APOE-ε4 allele on cognitive function vary across the lifespan: reduced memory and executive function have been found in older individuals but, paradoxically, young APOE-ε4 carriers perform better on cognitive tests and show higher neural efficiency. This study aimed to assess the association between APOE genotype and saccade latency using a prosaccade and antisaccade task in young individuals (N = 97, age: 17–35 years). Results showed that prosaccade latency was significantly delayed in a group of ε4 carriers in comparison to non-carriers, which was due to a lower rate of signal accumulation rather than a change in the criterion threshold. In contrast, there was no significant genotype difference for antisaccade latency in this young cohort. These results indicate that prosaccade latency may be useful in establishing the APOE behavioural phenotype, which could ultimately assist with distinguishing between normal and pathological aging.Propel Centre for Population Health Impact, University of Waterlo

Inherited variation in immune genes and pathways and glioblastoma risk

To determine whether inherited variations in immune function single-nucleotide polymorphisms (SNPs), genes or pathways affect glioblastoma risk, we analyzed data from recent genome-wide association studies in conjunction with predefined immune function genes and pathways. Gene and pathway analyses were conducted on two independent data sets using 6629 SNPs in 911 genes on 17 immune pathways from 525 glioblastoma cases and 602 controls from the University of California, San Francisco (UCSF) and a subset of 6029 SNPs in 893 genes from 531 cases and 1782 controls from MD Anderson (MDA). To further assess consistency of SNP-level associations, we also compared data from the UK (266 cases and 2482 controls) and the Mayo Clinic (114 cases and 111 controls). Although three correlated epidermal growth factor receptor (EGFR) SNPs were consistently associated with glioblastoma in all four data sets (Mantel–Haenzel P values = 1 × 10−5 to 4 × 10−3), independent replication is required as genome-wide significance was not attained. In gene-level analyses, eight immune function genes were significantly (minP < 0.05) associated with glioblastoma; the IL-2RA (CD25) cytokine gene had the smallest minP values in both UCSF (minP = 0.01) and MDA (minP = 0.001) data sets. The IL-2RA receptor is found on the surface of regulatory T cells potentially contributing to immunosuppression characteristic of the glioblastoma microenvironment. In pathway correlation analyses, cytokine signaling and adhesion–extravasation–migration pathways showed similar associations with glioblastoma risk in both MDA and UCSF data sets. Our findings represent the first systematic description of immune genes and pathways that characterize glioblastoma risk

A network analysis to identify mediators of germline-driven differences in breast cancer prognosis

cited By 0Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies similar to 7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.Peer reviewe

Incorporating progesterone receptor expression into the PREDICT breast prognostic model

Background: Predict Breast (www.predict.nhs.uk) is an online prognostication and treatment benefit tool for early invasive breast cancer. The aim of this study was to incorporate the prognostic effect of progesterone receptor (PR) status into a new version of PREDICT and to compare its performance to the current version (2.2).Method: The prognostic effect of PR status was based on the analysis of data from 45,088 European patients with breast cancer from 49 studies in the Breast Cancer Association Consortium. Cox proportional hazard models were used to estimate the hazard ratio for PR status. Data from a New Zealand study of 11,365 patients with early invasive breast cancer were used for external validation. Model calibration and discrimination were used to test the model performance.Results: Having a PR-positive tumour was associated with a 23% and 28% lower risk of dying from breast cancer for women with oestrogen receptor (ER)-negative and ER-positive breast cancer, respectively. The area under the ROC curve increased with the addition of PR status from 0.807 to 0.809 for patients with ER-negative tumours (p = 0.023) and from 0.898 to 0. 902 for patients with ER-positive tumours (p = 2.3 x 10(-6)) in the New Zealand cohort. Model calibration was modest with 940 observed deaths compared to 1151 predicted.Conclusion: The inclusion of the prognostic effect of PR status to PREDICT Breast has led to an improvement of model performance and more accurate absolute treatment benefit predic-tions for individual patients. Further studies should determine whether the baseline hazard function requires recalibration. (C) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Incorporating progesterone receptor expression into the PREDICT breast prognostic model

Background: Predict Breast (www.predict.nhs.uk) is an online prognostication and treatment benefit tool for early invasive breast cancer. The aim of this study was to incorporate the prognostic effect of progesterone receptor (PR) status into a new version of PREDICT and to compare its performance to the current version (2.2).Method: The prognostic effect of PR status was based on the analysis of data from 45,088 European patients with breast cancer from 49 studies in the Breast Cancer Association Consortium. Cox proportional hazard models were used to estimate the hazard ratio for PR status. Data from a New Zealand study of 11,365 patients with early invasive breast cancer were used for external validation. Model calibration and discrimination were used to test the model performance.Results: Having a PR-positive tumour was associated with a 23% and 28% lower risk of dying from breast cancer for women with oestrogen receptor (ER)-negative and ER-positive breast cancer, respectively. The area under the ROC curve increased with the addition of PR status from 0.807 to 0.809 for patients with ER-negative tumours (p = 0.023) and from 0.898 to 0. 902 for patients with ER-positive tumours (p = 2.3 x 10(-6)) in the New Zealand cohort. Model calibration was modest with 940 observed deaths compared to 1151 predicted.Conclusion: The inclusion of the prognostic effect of PR status to PREDICT Breast has led to an improvement of model performance and more accurate absolute treatment benefit predic-tions for individual patients. Further studies should determine whether the baseline hazard function requires recalibration. (C) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

ARTICLEAssociation of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival

Aim To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Methods Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. Results There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55–0.78)]. No association was observed with radiotherapy. Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09–1.56)]. Conclusion Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk

Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival

Background: Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers.Aim: To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS.Methods: Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. Results: There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55-0.78)]. No association was observed with radiotherapy.Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09-1.56)].Conclusion: Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk.Peer reviewe

Common variants in breast cancer risk loci predispose to distinct tumor subtypes.

BACKGROUND: Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. METHODS: Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. RESULTS: Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions. CONCLUSION: This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction