Statistics of Neuronal Identification with Open- and Closed-Loop Measures of Intrinsic Excitability

In complex nervous systems patterns of neuronal activity and measures of intrinsic neuronal excitability are often used as criteria for identifying and/or classifying neurons. We asked how well identification of neurons by conventional measures of intrinsic excitability compares with a measure of neuronal excitability derived from a neuron’s behavior in a dynamic clamp constructed two-cell network. We used four cell types from the crab stomatogastric ganglion: the pyloric dilator, lateral pyloric, gastric mill, and dorsal gastric neurons. Each neuron was evaluated for six conventional measures of intrinsic excitability (intrinsic properties, IPs). Additionally, each neuron was coupled by reciprocal inhibitory synapses made with the dynamic clamp to a Morris–Lecar model neuron and the resulting network was assayed for four measures of network activity (network activity properties, NAPs). We searched for linear combinations of IPs that correlated with each NAP, and combinations of NAPs that correlated with each IP. In the process we developed a method to correct for multiple correlations while searching for correlating features. When properly controlled for multiple correlations, four of the IPs were correlated with NAPs, and all four NAPs were correlated with IPs. Neurons were classified into cell types by training a linear classifier on sets of properties, or using k-medoids clustering. The IPs were modestly successful in classifying the neurons, and the NAPs were more successful. Combining the two measures did better than either measure alone, but not well enough to classify neurons with perfect accuracy, thus reiterating that electrophysiological measures of single-cell properties alone are not sufficient for reliable cell identification

Cancer Borealis Stomatogastric Nervous System Dissection

The stomatogastric ganglion (STG) is an excellent model for studying cellular and network interactions because it contains a relatively small number of cells (approximately 25 in C. borealis) which are well characterized. The cells in the STG exhibit a broad range of outputs and are responsible for the motor actions of the stomach. The stomach contains the gastric mill which breaks down food with three internal teeth, and the pylorus which filters the food before it reaches the midgut. The STG produces two rhythmic outputs to control the gastric mill and pylorus known as central pattern generators (CPGs). Each cell in the STG can participate in one or both of these rhythms. These CPGs allow for the study of neuromodulation, homeostasis, cellular and network variability, network development, and network recovery

Integrating Exposure Knowledge and Serum Suspect Screening as a New Approach to Biomonitoring: An Application in Firefighters and Office Workers.

Firefighters (FF) are exposed to recognized and probable carcinogens, yet there are few studies of chemical exposures and associated health concerns in women FFs, such as breast cancer. Biomonitoring often requires a priori selection of compounds to be measured, and so, it may not detect relevant, lesser known, exposures. The Women FFs Biomonitoring Collaborative (WFBC) created a biological sample archive and conducted a general suspect screen (GSS) to address this data gap. Using liquid chromatography-quadrupole time-of-flight tandem mass spectrometry, we sought to identify candidate chemicals of interest in serum samples from 83 women FFs and 79 women office workers (OW) in San Francisco. We identified chemical peaks by matching accurate mass from serum samples against a custom chemical database of 722 slightly polar phenolic and acidic compounds, including many of relevance to firefighting or breast cancer etiology. We then selected tentatively identified chemicals for confirmation based on the following criteria: (1) detection frequency or peak area differences between OW and FF; (2) evidence of mammary carcinogenicity, estrogenicity, or genotoxicity; and (3) not currently measured in large biomonitoring studies. We detected 620 chemicals that matched 300 molecular formulas in the WFBC database, including phthalate metabolites, phosphate flame-retardant metabolites, phenols, pesticides, nitro and nitroso compounds, and per- and polyfluoroalkyl substances. Of the 20 suspect chemicals selected for validation, 8 were confirmed-including two alkylphenols, ethyl paraben, BPF, PFOSAA, benzophenone-3, benzyl p-hydroxybenzoate, and triphenyl phosphate-by running a matrix spike of the reference standards and using m/z, retention time, and the confirmation of at least two fragment ions as criteria for matching. GSS provides a powerful high-throughput approach to identify and prioritize novel chemicals for biomonitoring and health studies

Association Between Concussion Burden During Professional American-Style Football and Postcareer Hypertension

Previous work has demonstrated an association between American-style football (ASF) and the development of hypertension among collegiate athletes.1 In addition, hypertension prevalence has been shown to be higher among active professional ASF athletes compared with similarly aged members of the general population.2 Whereas causal factors including deliberate weight gain, repetitive isometric strength training, sleep apnea, and nonsteroidal anti-inflammatory drug use have been suggested, definitive mechanisms remain incompletely understood. Recent studies in general populations have shown associations between brain injury and subsequent hypertension.3 Given that ASF players are at particular risk for recurrent head injury, the relationship between concussion history and later life hypertension deserves focused exploration

Premortem Chronic Traumatic Encephalopathy Diagnoses in Professional Football

American-style football (ASF) has gained attention because of possible links between repetitive head injury and neurodegenerative diseases. Although postmortem pathologic changes consistent with chronic traumatic encephalopathy (CTE) have been reported in ASF players, there are currently no established premortem diagnostic criteria for CTE. Nevertheless, presented with symptoms of cognitive impairment, clinicians treating former players may be inclined to suggest CTE without a thorough exploration of comorbid factors that demonstrate similar clinical phenotypes to putative CTE. A survey of 3,913 former ASF players aged 24 to 89 was conducted for those who responded by March 2019. Despite being a postmortem diagnosis, 108 players (2.8%) self-reported clinician-diagnosed CTE. The percentage of players under age 60 years reporting a CTE diagnosis was 2.3% versus 3.7% in participants age 60 or older. Comorbidities in participants self-reporting CTE were significantly more common, including sleep apnea, hypercholesterolemia, obesity, indicators of past or current depression, hypertension, prescription pain medication use, heart conditions, and low testosterone when compared to non-CTE respondents. Patterns of reporting for obesity, hypertension, heart conditions, or hypercholesterolemia differed between older and younger participants. Cognitive impairment symptoms were significantly higher in participants self-reporting CTE. Some former professional football players have been clinically diagnosed with CTE, a postmortem condition. Comorbidities that can affect cognition were associated with CTE diagnoses in both older and younger players. Although underlying neuropathology cannot be ruled out, treatable conditions should be explored in former athletes demonstrating CTE-linked clinical phenotypes or symptoms as a means of improving cognitive health in these patients. ANN NEUROL 2020 ANN NEUROL 2020;88:106-11

Social network structure and composition in former NFL football players

Social networks have broad effects on health and quality of life. Biopsychosocial factors may also modify the effects of brain trauma on clinical and pathological outcomes. However, social network characterization is missing in studies of contact sports athletes. Here, we characterized the personal social networks of former National Football League players compared to non-football US males. In 303 former football players and 269 US males, we found that network structure (e.g., network size) did not differ, but network composition (e.g., proportion of family versus friends) did differ. Football players had more men than women, and more friends than family in their networks compared to US males. Black players had more racially diverse networks than White players and US males. These results are unexpected because brain trauma and chronic illnesses typically cause diminished social relationships. We anticipate our study will inform more multi-dimensional study of, and treatment options for, contact sports athletes. For example, the strong allegiances of former athletes may be harnessed in the form of social network interventions after brain trauma. Because preserving health of contact sports athletes is a major goal, the study of social networks is critical to the design of future research and treatment trials

Race differences in pain and pain-related risk factors among former professional American-style football players

The burden of pain is unequal across demographic groups, with broad and persisting race differences in pain-related outcomes in the United States. Members of racial and ethnic minorities frequently report more pervasive and severe pain compared with those in the majority, with at least some disparity attributable to differences in socioeconomic status. Whether race disparities in pain-related health outcomes exist among former professional football players is unknown. We examined the association of race with pain outcomes among 3995 former professional American-style football players who self-identified as either Black or White. Black players reported more intense pain and higher levels of pain interference relative to White players, even after controlling for age, football history, comorbidities, and psychosocial factors. Race moderated associations between several biopsychosocial factors and pain; higher body mass index was associated with more pain among White but not among Black players. Fatigue and psychosocial factors were more strongly related to pain among Black players relative to White players. Collectively, the substantial social and economic advantages of working as a professional athlete did not seem to erase race-related disparities in pain. We highlight an increased burden of pain among elite Black professional football players and identify race-specific patterns of association between pain and biopsychosocial pain risk factors. These findings illuminate potential future targets of interventions that may serve to reduce persistent disparities in the experience and impact of pain.</p

Recent research on Gulf War illness and other health problems in veterans of the 1991 Gulf War: Effects of toxicant exposures during deployment

Veterans of Operation Desert Storm/Desert Shield - the 1991 Gulf War (GW) - are a unique population who returned from theater with multiple health complaints and disorders. Studies in the U.S. and elsewhere have consistently concluded that approximately 25-32% of this population suffers from a disorder characterized by symptoms that vary somewhat among individuals and include fatigue, headaches, cognitive dysfunction, musculoskeletal pain, and respiratory, gastrointestinal and dermatologic complaints. Gulf War illness (GWI) is the term used to describe this disorder. In addition, brain cancer occurs at increased rates in subgroups of GW veterans, as do neuropsychological and brain imaging abnormalities. Chemical exposures have become the focus of etiologic GWI research because nervous system symptoms are prominent and many neurotoxicants were present in theater, including organophosphates (OPs), carbamates, and other pesticides; sarin/cyclosarin nerve agents, and pyridostigmine bromide (PB) medications used as prophylaxis against chemical warfare attacks. Psychiatric etiologies have been ruled out. This paper reviews the recent literature on the health of 1991 GW veterans, focusing particularly on the central nervous system and on effects of toxicant exposures. In addition, it emphasizes research published since 2008, following on an exhaustive review that was published in that year that summarizes the prior literature (RACGWI, 2008). We conclude that exposure to pesticides and/or to PB are causally associated with GWI and the neurological dysfunction in GW veterans. Exposure to sarin and cyclosarin and to oil well fire emissions are also associated with neurologically based health effects, though their contribution to development of the disorder known as GWI is less clear. Gene-environment interactions are likely to have contributed to development of GWI in deployed veterans. The health consequences of chemical exposures in the GW and other conflicts have been called "toxic wounds" by veterans. This type of injury requires further study and concentrated treatment research efforts that may also benefit other occupational groups with similar exposure-related illnesses