Chronic traumatic encephalopathy: contributions from the Boston University Center for the Study of Traumatic Encephalopathy.

OBJECTIVE: Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease associated with repetitive brain trauma (RBT). Initially described in boxers, CTE has now been found in other contact sport athletes with a history of RBT. In recent years, there has been tremendous media attention regarding CTE, primarily because of the deaths of high profile American football players who were found to have CTE upon neuropathological examination. However, the study of CTE remains in its infancy. This review focuses on research from the Centre for the Study of Traumatic Encephalopathy (CSTE) at Boston University. METHODS: This study reviews the formation of the CSTE, major CSTE publications and current ongoing research projects at the CSTE. RESULTS: The neuropathology of CTE has been well-described. Current research focuses on: methods of diagnosing the disease during life (including the development of biomarkers), examination of CTE risk factors (including genetic susceptibility and head impact exposure variables); description of the clinical presentation of CTE; development of research diagnostic criteria for Traumatic Encephalopathy Syndrome; and assessment of mechanism and pathogenesis. CONCLUSIONS: Current research at the BU CSTE is aimed at increasing understanding of the long-term consequences of repetitive head impacts and attempting to begin to answer several of the unanswered questions regarding CTE.

Current understanding of chronic traumatic encephalopathy.

OPINION STATEMENT: Chronic traumatic encephalopathy (CTE) is a unique neurodegenerative disease found in individuals with a history of repetitive head impacts. The neuropathology of CTE is increasingly well defined. Prospective, longitudinal studies with post-mortem neuropathologic validation as well as in vivo diagnostic techniques are needed in order to advance the understanding of CTE clinically. Given the large number of individuals who incur concussions and other forms of brain trauma, this is an important area for scientific and public health inquiry.

Self-reported concussion history: impact of providing a definition of concussion.

BACKGROUND: In recent years, the understanding of concussion has evolved in the research and medical communities to include more subtle and transient symptoms. The accepted definition of concussion in these communities has reflected this change. However, it is unclear whether this shift is also reflected in the understanding of the athletic community. WHAT IS KNOWN ABOUT THE SUBJECT: Self-reported concussion history is an inaccurate assessment of someone's lifetime exposure to concussive brain trauma. However, unfortunately, in many cases it is the only available tool. HYPOTHESIS/PURPOSE: We hypothesize that athletes' self-reported concussion histories will be significantly greater after reading them the current definition of concussion, relative to the reporting when no definition was provided. An increase from baseline to post-definition response will suggest that athletes are unaware of the currently accepted medical definition. STUDY DESIGN: Cross-sectional study of 472 current and former athletes. METHODS: Investigators conducted structured telephone interviews with current and former athletes between January 2010 and January 2013, asking participants to report how many concussions they had received in their lives. Interviewers then read participants a current definition of concussion, and asked them to re-estimate based on that definition. RESULTS: THE TWO ESTIMATES WERE SIGNIFICANTLY DIFFERENT (WILCOXON SIGNED RANK TEST: z=15.636, P<0.001). Comparison of the baseline and post-definition medians (7 and 15, respectively) indicated that the post-definition estimate was approximately twice the baseline. Follow-up analyses indicated that this effect was consistent across all levels of competition examined and across type of sport (contact versus non-contact). CONCLUSION: Our results indicate that athletes' current understandings of concussions are not consistent with a currently accepted medical definition. We strongly recommend that clinicians and researchers preface requests for self-reported concussion history with a definition. In addition, it is extremely important that researchers report the definition they used in published manuscripts of their work. WHAT THIS STUDY ADDS TO EXISTING KNOWLEDGE: Our study shows that unprompted reporting of concussion history produces results that are significantly different from those provided after a definition has been given, suggesting one possible mechanism to improve the reliability of self-reported concussion history across multiple individuals.

Repetition-related reductions in neural activity reveal component processes of mental simulation.

In everyday life, people adaptively prepare for the future by simulating dynamic events about impending interactions with people, objects and locations. Previous research has consistently demonstrated that a distributed network of frontal-parietal-temporal brain regions supports this ubiquitous mental activity. Nonetheless, little is known about the manner in which specific regions of this network contribute to component features of future simulation. In two experiments, we used a functional magnetic resonance (fMR)-repetition suppression paradigm to demonstrate that distinct frontal-parietal-temporal regions are sensitive to processing the scenarios or what participants imagined was happening in an event (e.g., medial prefrontal, posterior cingulate, temporal-parietal and middle temporal cortices are sensitive to the scenarios associated with future social events), people (medial prefrontal cortex), objects (inferior frontal and premotor cortices) and locations (posterior cingulate/retrosplenial, parahippocampal and posterior parietal cortices) that typically constitute simulations of personal future events. This pattern of results demonstrates that the neural substrates of these component features of event simulations can be reliably identified in the context of a task that requires participants to simulate complex, everyday future experiences.

Imagine all the people: how the brain creates and uses personality models to predict behavior.

The behaviors of other people are often central to envisioning the future. The ability to accurately predict the thoughts and actions of others is essential for successful social interactions, with far-reaching consequences. Despite its importance, little is known about how the brain represents people in order to predict behavior. In this functional magnetic resonance imaging study, participants learned the unique personality of 4 protagonists and imagined how each would behave in different scenarios. The protagonists' personalities were composed of 2 traits: Agreeableness and Extraversion. Which protagonist was being imagined was accurately inferred based solely on activity patterns in the medial prefrontal cortex using multivariate pattern classification, providing novel evidence that brain activity can reveal whom someone is thinking about. Lateral temporal and posterior cingulate cortex discriminated between different degrees of agreeableness and extraversion, respectively. Functional connectivity analysis confirmed that regions associated with trait-processing and individual identities were functionally coupled. Activity during the imagination task, and revealed by functional connectivity, was consistent with the default network. Our results suggest that distinct regions code for personality traits, and that the brain combines these traits to represent individuals. The brain then uses this "personality model" to predict the behavior of others in novel situations.

Clinical presentation of chronic traumatic encephalopathy.

OBJECTIVE: The goal of this study was to examine the clinical presentation of chronic traumatic encephalopathy (CTE) in neuropathologically confirmed cases. METHODS: Thirty-six adult male subjects were selected from all cases of neuropathologically confirmed CTE at the Boston University Center for the Study of Traumatic Encephalopathy brain bank. Subjects were all athletes, had no comorbid neurodegenerative or motor neuron disease, and had next-of-kin informants to provide retrospective reports of the subjects' histories and clinical presentations. These interviews were conducted blind to the subjects' neuropathologic findings. RESULTS: A triad of cognitive, behavioral, and mood impairments was common overall, with cognitive deficits reported for almost all subjects. Three subjects were asymptomatic at the time of death. Consistent with earlier case reports of boxers, 2 relatively distinct clinical presentations emerged, with one group whose initial features developed at a younger age and involved behavioral and/or mood disturbance (n = 22), and another group whose initial presentation developed at an older age and involved cognitive impairment (n = 11). CONCLUSIONS: This suggests there are 2 major clinical presentations of CTE, one a behavior/mood variant and the other a cognitive variant.

Interactions between visual attention and episodic retrieval: dissociable contributions of parietal regions during gist-based false recognition.

The interaction between episodic retrieval and visual attention is relatively unexplored. Given that systems mediating attention and episodic memory appear to be segregated, and perhaps even in competition, it is unclear how visual attention is recruited during episodic retrieval. We investigated the recruitment of visual attention during the suppression of gist-based false recognition, the tendency to falsely recognize items that are similar to previously encountered items. Recruitment of visual attention was associated with activity in the dorsal attention network. The inferior parietal lobule, often implicated in episodic retrieval, tracked veridical retrieval of perceptual detail and showed reduced activity during the engagement of visual attention, consistent with a competitive relationship with the dorsal attention network. These findings suggest that the contribution of the parietal cortex to interactions between visual attention and episodic retrieval entails distinct systems that contribute to different components of the task while also suppressing each other.

Retrieval Failure Contributes to Gist-Based False Recognition.

People often falsely recognize items that are similar to previously encountered items. This robust memory error is referred to as gist-based false recognition. A widely held view is that this error occurs because the details fade rapidly from our memory. Contrary to this view, an initial experiment revealed that, following the same encoding conditions that produce high rates of gist-based false recognition, participants overwhelmingly chose the correct target rather than its related foil when given the option to do so. A second experiment showed that this result is due to increased access to stored details provided by reinstatement of the originally encoded photograph, rather than to increased attention to the details. Collectively, these results suggest that details needed for accurate recognition are, to a large extent, still stored in memory and that a critical factor determining whether false recognition will occur is whether these details can be accessed during retrieval.