Randy J. Nelson
Brumbaugh Chair in Brain Research and Teaching
Professor and Chair, Department of Neuroscience
Distinguished Professor, College of Medicine
The Ohio State University Wexner Medical Center
9:45 – 10:30 am
Morning Keynote Address
"Effects of Light at Night on Neuroinflammation, Metabolism and Mood"
Technological advances, while providing many benefits, often create circumstances that differ from the conditions in which we evolved. With the wide-spread adoption of electrical lighting during the 20the century, humans became exposed to bright and unnatural light at night for the first time during their evolutionary history. Electrical lighting has led to the wide-scale practice of 24-hour shift-work and has meant that what were once just "daytime" activities run throughout the night; in many ways, Western society now functions on a 24-hour schedule. Recent research suggests that this gain in freedom to function throughout the night may also come with significant repercussions. Disruption of our naturally evolved light and dark cycles can result in a wide range of physiological and behavioral changes with potentially serious medical implications. In this presentation the disruptive effects of light at night on several core clock genes and the resulting Neuroinflammation will be discussed. Increased brain inflammation may be a potent mechanism through which light at night affects mood and food intake.
Professor, Biological Sciences
Kent State University
10:30 – 11:00 am
"Ethanol Disrupts Biological Clock Timing: Considering Alcoholism as a Circadian-based Disease"
Alcohol abuse leads to marked disruptions of sleep and circadian rhythms. These disturbances can promote excessive drinking, resulting in a cycle of circadian dysfunction and increasing alcohol intake. Here we summarize our complimentary studies demonstrating the actions of ethanol on critical systems that regulate the circadian clock of the suprachiasmatic nucleus (SCN). In vivo. In hamsters and mice, acute ethanol administration inhibits the phase-resetting effect of light on circadian behavioral rhythms. This treatment also impairs non-photic phase-shifting mediated by serotonergic stimulation. Intra-SCN administration of ethanol also blocks photic shifting. Ethanol also disrupts entrainment to a weak skeleton photoperiod, but not to a normal light-dark cycle. In vitro. Similar to the in vivo trials, ethanol treatment of SCN-containing brain slices blocks photic-like (glutamate-induced) phase shifts of clock-driven circadian neuronal activity. This effect is dose-dependent and is blocked by BDNF pre-treatment. Ethanol modulation of glutamatergic and serotonergic phase resetting exhibits acute tolerance, as 15-30 min ethanol pretreatment blocks these effects. Ethanol also modulates GABAergic phase-resetting in the SCN, likely through enhanced signaling of subunit-containing GABA receptors. The SCN also exhibits rapid (24 h) ethanol tolerance, as assessed through glutamate phase resetting in tissue from ethanol-consuming mice. Together, these results confirm ethanol's significant disruption of SCN photic and non-photic phase-resetting responses. These effects involve direct actions of ethanol in SCN serotonergic, glutamatergic, BDNF, and GABAergic signaling. These results imply that alcohol abuse and alcoholism should be considered in the context of circadian-based pathology. Interventions that strengthen circadian rhythm structure (i.e. appropriately-timed exercise and/or bright light exposure) should be implemented alongside conventional treatments. Supported by NIH AA-015948 and AA-017898 grants.
Associate Professor, Department of Psychiatry, Translational Neuroscience Program
University of Pittsburgh School of Medicine
11:00 – 11:30 am
"Circadian Genes, Rhythms and the Biology of Mood Disorders"
Mood disorders are serious diseases that affect a large portion of the population. Nearly all people suffering from mood disorders have significant disruptions in circadian rhythms and the sleep/wake cycle. In fact altered sleep patterns are one of the major diagnostic criteria for these disorders. Moreover, environmental disruptions to circadian rhythms including shift work, overseas travel, and irregular social schedules tend to precipitate or exacerbate mood-related episodes. Recent studies have found that molecular clocks are found throughout the brain and body where they participate in the regulation of most physiological processes, including those thought to be involved in mood regulation. This seminar will summarize the evidence linking circadian rhythm disruptions with mood disorders, including the circadian rhythm abnormalities that tend to associate with specific disorders, as well as the effect of current treatments on rhythms. Moreover, I will summarize recent data which implicates the circadian system as a vital regulator dopaminergic signaling which is important in the regulation of mood and reward-related behavior.
Associate Professor, Department of Cellular and Molecular Pharmacology
Rosalind Franklin University of Medicine and Science
11:30 – Noon
"Adolescence: A Period of Increased Vulnerability to Cocaine Addiction"
In humans, adolescence is a period of heightened propensity for cocaine addiction. It is unknown if this is due to greater access/exposure to cocaine at this age, or if the adolescent brain is particularly susceptible to addiction. We determined if adolescent rats show elevated activity of midbrain dopamine neurons, a trait associated with heightened susceptibility to addiction. Dopamine neuron activity showed an inverted U-shaped curve from weaning to adulthood, with peak activity during adolescence. Heightened dopamine neuron activity during adolescence was observed both in vivo, with extracellular recordings in anesthetized rats, and ex vivo, with cell-attached recordings from midbrain slices. In adolescents, GABA-A receptor-mediated sIPSCs occurred at lower frequency and smaller amplitudes, suggesting a possible mechanism underlying heightened dopamine neuron activity during adolescence. Elevated dopamine neuron activity during adolescence was associated with elevated addiction liability according to DSM-IV criteria, tested with intravenous cocaine self-administration. Increased cocaine self-administration in adolescents could be reversed by administering drugs that modify dopamine neuron activity, suggesting a causal relationship between these electrophysiological and behavioral determinants of cocaine addiction. In conclusion, these studies demonstrate that neurophysiological differences during development underlie the heightened addiction liability observed during adolescence.
Ralph and Luci Shey Chair
Director of the Schey Center for Cognitive Neuroimaging, Lou Ruvo Center for Brain Health
Cleveland Clinic Foundation
2:45 – 3:15
"Strategies for the Preclinical Detection and Prevention of Alzheimer's Disease"
The neuropathological changes associated withAlzheimer's disease (AD) are thought to begin decades prior to the advent of symptoms. By the time AD is diagnosed, patients have experienced widespread cognitive impairment and extensive brain atrophy. Interventions administered at this stage may be too late to alter the disease trajectory. This recognition has prompted investigators in the field to consider prevention trials involving cognitively intact individuals at genetic risk for AD. The first wave of such preventions trials will focus on persons with the autosomal-dominant mutation variant of AD, since it is possible to determine with certainty that the participant will develop AD. Should these prevention trials identify an agent that alters the disease course during the preclinical phase; the next step will be to enroll cognitively intact elders at risk for the more common, sporadic form of AD. Prior to conducting a prevention trial in sporadic AD, it is essential to validate biomarkers for purposes of accurately identifying persons at risk for AD during the preclinical phase and for monitoring treatment response since such individuals are by definition asymptomatic. Several candidate biochemical, anatomical, and functional biomarkers have shown promise, but vary in their ease of administration, availability, safety, accuracy, reproducibility, and invasiveness. Among these candidate biomarkers, task-activated functional magnetic resonance imaging (fMRI) is a promising approach that is noninvasive, carries little risk, and offers a high potential for identifying persons who may eventually develop AD. My fMRI research program has examined brain circuits involved in semantic memory using a famous name recognition. We have demonstrated that the presence of the apolipoprotein-E (APOE) ε4 allele and a family history of dementia are associated with increased activation in several key AD-related brain regions (e.g., hippocampus, posterior cingulate, inferior parietal), suggesting its possible role as a marker for disease risk and progression during the preclinical stage. The value of task-activated fMRI for monitoring treatment efficacy will also be discussed in the context of a prevention trial involving cognitive training and aerobic exercise interventions.
Associate Professor, Department of Psychology
Kent State University
3:15 – 3:45
"Can weight loss reduce your risk of Alzheimer's disease?"
Obesity is linked to many adverse brain changes, including accelerated cognitive decline and Alzheimer's disease. Less clear is the possibility that obesity-related cognitive dysfunction could be reversed through significant weight loss. Obesity is associated with many conditions with partly reversible cognitive deficits, including hypertension, type 2 diabetes, sleep apnea, and depression. Our team is examining this possibility by prospectively assessing cognitive function in persons that undergo bariatric surgery. Interestingly, patients show improved memory function after bariatric surgery and these improvements persist over time. Future studies are much needed to determine whether these cognitive benefits persist at later follow-up (e.g. 60 months) when weight re-gain is common and the degree to which bariatric surgery may reduce risk for Alzheimer's disease or other neurological disorders in older adulthood.
Professor of Psychiatry
Boston University School of Medicine and Lecturer in Psychiatry, Harvard Medical School
3:45 – 4:15
"When Brain Injury and Psychological Trauma Co-Occur: Can we Disentangle the Consequences?"
The wars in Iraq and Afghanistan have highlighted the often complex clinical outcomes of traumatic brain injury events that occur within the context of exposure to extreme psychological stress. Traumatic brain injuries embedded within psychological trauma are not limited to military contexts, however, and also include such events as physical assault, industrial accidents, and motor vehicle accidents. This presentation will discuss the potential contributions of traumatic brain injury and psychological trauma to neuropsychological outcomes, as well as their potential neural overlap. The presentation will emphasize mild brain injuries, with data presented from a longitudinal study of neuropsychological outcomes of U.S. Army soldiers deployed to Iraq early in the war. A conceptual model of how psychological trauma, traumatic brain injury, and their consequences may adversely affect recovery will also be presented.
Kenan Distinguished Professor
Director, Matthew Gfeller Sport-Related Traumatic Brain Injury Research Center
The University of North Carolina at Chapel Hill
5:30 – 6:30
Evening Keynote Address
"Making Sport Safer Through Innovative Science."
Sport-related concussion is one of the most complex injuries facing sports medicine clinicians charged with making sound return to play decisions. There are many pieces to the concussion puzzle, and until recently, the biomechanics of concussion has been largely ignored. Although recent studies of collegiate football players and youth ice hockey players indicate that the biomechanical threshold for concussive injury is still illusive, tracking head impacts in real time and translating the findings into models for injury prevention is improving safety. This presentation aims to summarize findings from these recently conducted studies investigating biomechanical relationships with various factors such as playing position, types of play, concussive vs sub-concussive impacts, location of impacts, and clinical measures of concussion. Combining the biomechanical findings of active athletes with those of retired professional athletes, may allow us to better understand the long-term consequences of concussive and sub-concussive impacts to the head.