The Bradford Reproducibility, Affect, and Drugs Laboratory
Welcome to the BRAD-LAB! We are part of the Psychology Department at the University of Miami. We take a multi-method experimental approach to studying the affective and emotional responses to stressors and how commonly used drugs change those responses. We study the mechanisms of these responses by assessing their neurobiological, cognitive, and behavioral components. We want to learn how responses to stressors are important in mental health challenges such as addiction and anxiety so we can better treat such challenges. Because we want to get to the truth in our research, we approach our work with an eye to rigor and replicability consistent with the “reproducibility revolution” and open science movement. You can read the unusual story of our lab’s name here.
Consistent with our lab’s commitment to open source tools, this website was made in R Studio using R Markdown and the Hugo Academic Theme
Our program of research takes a multi-measure experimental psychopathology approach to better understand the role of stress reactivity in mental health. In this research, we focus on psychological processes at the interface of affect and addiction. We use novel experimental tasks with precise manipulation of laboratory stressors, pharmacological challenges and psychophysiological measures that allow tight translation between animal and human research. Though we study human populations, our approach builds on preclinical findings in animals to identify specific stressor characteristics and neurobehavioral, cognitive, and affective mechanisms of reactivity to stressors key in the understanding of stress reactivity in human psychopathology. This mechanistic understanding may provide novel targets for prevention and treatment of the negative impacts of acute and chronic drug use as well as comorbid anxiety and depression.
Rodent addiction models suggest that alcohol and other drugs dampen activity of the neural pathways involved in defensive stressor reactivity. Following chronic and heavy use in rodents, neuroadaptation in these pathways appears to increase this defensive reactivity. We contribute to a theoretical framework suggesting that this neuroadaptation occurs in human addiction as well, with increases in negative affect and other reactivity motivating more drug use. Indeed, humans have used drugs such as alcohol for millennia to alleviate acute negative affective and other responses to psychological stressors; however, alcohol does not diminish reactivity to all stressors equally. In fact, the stressor characteristics that contribute most to alcohol’s stress dampening effects remain unclear despite 30 years of observational and experimental research. As such, clear evidence for alcohol’s effects on stressor reactivity which may serve as the first step in alcohol-induced neuroadaptations in humans is elusive. In addressing this gap, we have noted that the neural structures (e.g., sub-nuclei within the central extended amygdala) and transmitter systems (e.g., corticotropin releasing factor and norepinephrine) implicated in animal addiction models overlap with those that modulate defensive reactivity during uncertain stressors. This defensive reactivity is measured using the innate, cross species, startle response to auditory probes during presentation of visual “threat cues” that signal delivery of both certain and uncertain electric shock stressors. The startle response during threat cues is potentiated above responses during no-threat cues (i.e., startle potentiation). Anxiolytic drugs (e.g., benzodiazepines) have a greater dampening effect on startle potentiation during uncertain vs certain stressors in humans. Using startle potentiation with complementary measures of affect and attention such as Event Related Potentials, our lab conducts programmatic studies to test for neuroadaptations in humans by examining 1) The effects of commonly used drugs on stressor-relevant mechanisms in healthy, non-dependent recreational users and 2) Evidence for adaptations or other perturbances in these stressor mechanisms in drug-dependent samples. We also maintain supplementary focus on 3) Empirical refinement of psychophysiology methods and the improvement of clinical psychological science broadly. We recognize that substantive advancement in my main areas of research requires rigorous, transparent, and programmatic practices.
How and under what circumstances commonly used drugs reduce reactivity to stressors
In a study published in Psychological Science (discussed in an accessible way in an article by the Huffington Post), we tested the hypothesis that alcohol would have a greater stress reducing effect during stressors of uncertain versus certain intensity. We administered various doses of alcohol to manipulate participants’ blood alcohol concentrations across a broad range of levels from sobriety to moderately high intoxication (approximately six standard drinks over 1 hour in a 180-pound man). We used startle potentiation and self-reported anxiety to index objective and subjective reactions to laboratory stressors (uncertain, high, and low electric shock). As you can see in the figure above, certain high intensity stressors elicited greater negative affect than certain low intensity stressors. This appears to confirm the old proverb, “better the devil you know than the devil you don’t know”. Alcohol’s effects on participants’ stress response were robust and linear across all stressor types with higher alcohol doses leading to lower stress responding. Alcohol’s effects on stress response were comparable across the high and low intensity stressors. However, we demonstrated that greater alcohol stress response dampening occurs during stressors of uncertain intensity compared to that during stressors of certain high and low intensity. Intoxicated drinkers may be less anxious about “the devil you don’t know” than about “the devil you know,” which in turn may lead to increases in certain types of risk taking when people drink. Of note, compensatory neuroadaptation in the response to uncertain stressors following chronic alcohol or other drug use and early chronic stress have been implicated in addiction. While most of this work has used animal models, our results represent a first step towards demonstration of the initial press for such neuroadaptation in humans following acute alcohol use.
Probing for evidence for neuroadaptations in stress circuits
Alcohol administration studies such as the one described above provide evidence in humans for the first component of neuroadaptation of uncertain stressor reactivity implicated by rodent models of drug dependence. In another study published in Journal of Abnormal Psychology, we examined startle potentiation during uncertain and certain stressors in a sample of recently abstinent (1-8 weeks) alcoholics and non-alcoholic controls. We found that individuals with alcohol use disorder (AUD) show exaggerated defensive response to uncertain but not certain stressors. This provided the first preliminary support for later stage of uncertainty-relevant stress neuroadaptations seen in rodent models. Practically speaking, excessive use of alcohol when “drinking to cope” may lead to exaggerated stressor reactivity, which may cause, maintain, or exacerbate AUD and other disorders.
Empirically based improvement of psychophysiology and psychological science
Concerns from the research community and public about the replicability of psychological science have spurred calls to increase the rigor and transparency of our field. We attempt to answer these calls by using increasingly larger sample sizes in experimental paradigms with all relevant physiological processing and analysis parameters preregistered and all data shared openly. We have also published empirical studies providing evidence-based approaches to establishing proper quantification and measurement of psychophysiological signals used to study psychological processes. Psychophysiological tasks such as the ones used in our research are poised to become a major contributor to NIMH RDoC and related initiatives in experimental medicine. They also align well with NIMH’s current priorities in experimental therapeutics including focus on mechanisms in clinical trials and the use of surrogate end points for treatment development, and endophenotype identification. For these tasks to contribute meaningfully, however, proper standards for their measurement and quantification must be established. Furthermore, their psychometric properties must be understood for them to be well positioned as tools in psychological research. Our efforts thus far have contributed to a clear and comprehensive empirical evaluation of the advantages and limitations of combinations of several measures, tasks, and quantification approaches used in affective and clinical science. In addition to empirical studies, we contribute to methodological themed commentaries published in high profile outlets such as Nature Human Behavior and Neuropsychopharmocology.
Bradford, D.E., Motschman, C.A., Starr, M.J., Curtin, J.J. (2017). Alcohol’s effects on emotionally motivated attention, defensive reactivity, and subjective anxiety during uncertain threat. Social Cognitive and Affective Neuroscience, 12(11), 1823–1832.doi:10.1093/scan/nsx095. PDF OSF
Moberg, C.A., Bradford, D.E., Kaye, J.T., Curtin, J.J. (2017). Increased startle potentiation to unpredictable stressors in alcohol dependence: Possible stress neuroadaptation in humans. Journal of Abnormal Psychology, 126(4), 441-453.doi: 10.1037/abn0000265. PDF OSF
Kaye J.T., Bradford D.E., Magruder K.P., Curtin J.J. (2017). Probing for neuroadaptations to unpredictable stressors in addiction: translational methods and emerging evidence. Journal of Studies on Alcohol and Drugs, 78(3).353-371. doi: 10.15288/jsad.2017.78.353.
Kaye J.T., Bradford D.E., Curtin J.J.(2016). Psychometric properties of startle and corrugator response in NPU, Affective Picture Viewing, and Resting State Tasks. Psychophysiology, 53(8).1241-1255.doi.org/10.1111/psyp.12794. PDF OSF
Bradford, D.E., Curtin, J.J., Piper, M.E. (2015). Anticipation of smoking sufficiently lowers stress reactivity for nicotine deprived smokers. Journal of Abnormal Psychology, 124(1), 128-136. doi:10.1037/abn0000007. PDF
Bradford, D.E., Starr, M.J., Shackman, A.J., Curtin, J. J. (2015). Empirically-based comparisons of the reliability and validity of common quantification approaches for eyeblink startle potentiation in humans. Psychophysiology,52(12), 1669-1681. doi: 10.1111/psyp.12545 PDF OSF
Green, C.S., Eichenbaum, A., Kattner, F., Bradford, D.E.,Gentile, D.A., Choo, H., Hsueh, V., Chen, H., Khoo, A. (2015). The role of game genres and the development of internet gaming disorder in school-aged children. Journal of Addictive Behaviors, Therapy & Rehabilitation 4(3),doi:10.4172/2324-9005.1000141
Eichenbaum, A., Kattner, F.,Bradford, D.E., Gentile, D.A., Green, C.S. (2015). Role-playing and real-time strategy games associated with greater probability of internet gaming disorder. Cyberpsychology, Behavior, and Social Networking 18(8), 480-485. doi:10.1089/cyber.2015.0092
Bradford, D.E., Kaye, J.T., Curtin, J.J. (2014). Not just noise: Individual differences in general startle reactivity predict startle reactivity to uncertain and certain threat. Psychophysiology,51(5), 707-411. doi:10.1111/psyp.12193. PDF
Bradford, D.E., Magruder, K.P., Korhumel, R.A., Curtin, J.J. (2014). Using the threat probability task to assess anxiety and fear to uncertain and certain threat. Journal of Visualized Experiments(91). doi:10.3791/51905. PDF Video
Lissek, S., Bradford, D.E., Alvarez, R.P., Burton, P., Espensen-Sturges, T., Reynolds,R.C., and Grillon, C. (2014). Neural substrates of classically conditioned fear-generalization in humans: A parametric fMRI study. Social Cognitive and Affective Neuroscience, 9(8), 1134-1142. doi:10.1093/scan/nst096.
Bradford, D.E., Shapiro, B.L., Curtin, J.J. (2013). How bad could it be? Alcohol dampens stress responses to threat of uncertain intensity. Psychological Science, 24(12), 2541-2549. doi:10.1177/0956797613499923. PDF
Lissek, S., Rabin S., McDowell D., Dvir S., Bradford, D.E., Geraci, M., Pine, S., Grillon, C., (2009). Impaired discriminative fear-conditioning resulting from elevated fear-responding to learned safety cues among individuals with panic disorder. Behaviour Research and Therapy, 47(2), 111–118. doi:10.1016/j.brat.2008.10.017
Much of our statement on lab values is inspired/borrowed by my colleague and good friend, Dr. Fallon Goodman’s lab.
Though science is fun and exciting, it can also be hard and stressful. Individuals also have their own unique challenges intrinsic to their circumstance. Our lab is committed to viewing each member as a whole person with a life both inside and outside of the lab. We operate from the assumption that in a person’s life—and perhaps during their time in our lab—there will be significant life stressors. Our mindset is that in order to have successful and meaningful careers, these stressors cannot be ignored. Rather, each individual and all of their stories are to be accepted and integrated in the fiber of our lab. By joining the lab, you are committing to the spirit of this community and its fellow lab members.
Dr Bradford’s mentoring style:
As the director of this lab, I am committed to supporting each member first and foremost as a complex, evolving, human being. I prioritize being available to lab members during both regular and often non-regular hours. In my view, this availability does not end when the lab member graduates or moves out of the state. I stay connected to many of my previous mentees for many years after the formal mentoring relationship has completed. I believe it is a mentor’s responsibility to be flexible and adjust to mentee’s needs within the mentoring relationship. This adjustment includes both the mentor and mentee finding the best way to communicate with one another. None of this means that I will not encourage lab members to grow and become independent. In fact, I have high expectations for and place large responsibility on lab members. I simply commit to supporting lab members as they carry and foster those expectations and responsibility.
The science we do in the lab is complex. I believe it is crucial to present this material in the clearest possible way. Despite some of the words used in the research descriptions on this website, I am careful to avoid scientific jargon and make attempts to use plain language in the lab. While helping lab members to strive for a fuller understanding of the data they consume, I encourage them to look for bias in the ways data may be presented in media reports that can obscure important shortcomings or caveats to our and others’ research.
I am proud to have had my mentoring recognized by receiving the 2017 Excellence in Undergraduate Mentoring Award from the Office of the Provost at University of Wisconsin, Madison. My contributions to mentoring students from diverse backgrounds was also recognized by the Multicultural Graduate Network with an honorable mention for their Peer Mentor Award. I am new to the University of Miami as of January 2020. As such, I am happy to provide references to my mentoring by mentees from my previous universities.
Reproducibility, Rigor, Transparency, and Openness:
Fifteen years ago, during a heated debate, my coworker angrily spoke words that still echo in my mind: “Psychology is a pseudoscience.” These words illustrate a common stigma that psychology’s merit is not up to par with the hard sciences, something that threatens the standing of psychological research in the public eye. Today, this threat is amplified by widespread concerns about the reproducibility of psychological science and more broadly, societal shifts towards a “post truth era.” Unfortunately, negative public perception about psychology can also discourage people from seeking much-needed psychological treatment. Consequently, stigma surrounding mental illness persists. Our lab is committed to fighting these issues, among others, through doing careful, rigorous, and transparent science. We aim to increase our understanding of human behavior while simultaneously remaining critical consumers and reliable disseminators of research. Most of our research is programmatic meaning we do multiple studies on the same topic and use careful internal replications. For many of our studies, we preregister our analysis parameters and openly share our data and analysis code.
Skills and experiences you can gain in our lab:
If you are in the lab for at least two semesters, you will have the opportunity to receive instruction and gain valuable experience using multiple tools used in clinical and experimental psychology including software such as R statistical computing platform and MATLAB as well as psychophysiology measurement techniques such as Electroencephalogram (EEG), Event Related Potentials (ERP), Electromyography (EMG) and Electrode Dermal Analysis (EDA). You will also likely have the opportunity to learn psychopharmacology techniques such as safe dosing of ethyl alcohol and measurement of Blood Alcohol Content (BAC). All of these skills will be taught with an eye to Open Science practices.
The U of Miami Psychology Department has a tradition of recognizing our different species family members
grabbing my toys and throwing them up in the air and running after them, swimming in the pool, swimming in the ocean
Playing with wires and string, Catnip, Catching bugs
Barking, Guarding, Cold weather, Running, Sleeping, Chewing
Napping, Being carried like a baby, Playing fetch, Chewing bones
Sleeping, Begging for food
Cuddling, Chasing my ball, Long car rides with the window down
If you are interested in joining the BRAD-LAB as a graduate student, please note:
Dr. Bradford reads all applications fully. It should be noted that the psychology programs at the university of Miami are competitive. As such, successful applicants typically have higher than average GRE scores, GPAs, and at least 2 years of research experience. It is also preferable to have strong letters of recommendation. Though authorship on publications are not expected, some demonstration of scientific writing ability and/or presentation experience is preferred. Again, Dr. Bradford reads all applications fully. If you have strong interest in our lab and believe your application would be considered less competitive for any of the reasons above, please either ask one of your letter writers to address this in their recommendation or you can speak to this in your personal statement.
More specific to our lab, applicants that appear familiar with the research we are doing and have interests that are aligned with our current research will be most competitive for our lab. Because our lab uses modern and sophisticated methods, applicants must be interested in learning about and acquiring the necessary expertise to use computing programs such as R and MATLAB. Finally, applicants with interest in Open Science theory and practice will fit best with our lab. Prospective students are encouraged to contact Dr. Bradford with any questions. You can apply to the clinical psychology program at University of Miami here.
If you are interested in joining the BRAD-LAB as a volunteer or for research credit, please answer the following questions in an email to Dr. Bradford, email@example.com:
Which are you interested in: volunteering or getting credit for research in the lab?
What days and hours are you typically available to work in the lab (it’s ok if you are not sure yet when you email)?
Why are you interested in working in this lab?
What do you think you can contribute to this lab?
Have you worked in other labs? Please list and describe your experience.
Feel free to say anything else you think would be helpful.
If you have a resume or CV, please attach it to your email.