Brianne Kent (PhD)
Brianne A Kent (PhD)
I am a translational neuroscientist, combining fundamental and clinical research to study how disrupted circadian rhythms and sleep contribute to the memory loss associated with Alzheimer's disease. I trained as a neuroscientist at Simon Fraser University (BA, 2009), Yale University (MSc 2010, MPhil 2011), the University of Cambridge (PhD, 2015), and the University of British Columbia (postdoc 2015-2019). I am currently a Research Fellow in the Division of Sleep and Circadian Disorders at Brigham and Women's Hospital and Harvard Medical School, funded by an NIH-NINDS K99/R00 Pathway to Independence Award. I am working to develop new methods for studying circadian rhythms in elderly and patients with Alzheimer's disease to assess how disrupted rhythms contribute to the disease.
In January 2021, I will be joining the Department of Psychology at Simon Fraser University (Vancouver, Canada) as an Assistant Professor. My research group will use translational neuroscience methodology to study causal mechanisms in rodent models with complementary studies in humans. I am currently recruiting graduate students. Please email firstname.lastname@example.org if you are interested in joining my research group. More information about the Cognitive and Neural Sciences Masters and PhD Program can be found here (deadline Dec 1, No GRE required).
Alzheimer's disease and other dementias threaten to become one of the greatest public health challenges of the 21st century, with an increasing number of aging people throughout the world at risk. As a translational neuroscientist, my research bridges basic science and clinical application.
Sleep and Circadian Rhythms in Alzheimer’s Disease
Alzheimer’s disease (AD) is the most common cause of dementia. AD is clinically heterogeneous, with numerous risk factors that affect its clinical and neuropathologic course. The hallmark neuropathology of AD is the accumulation of extracellular deposits of amyloid beta (Aβ) and intraneuronal accumulation of hyperphosphorylated tau, which lead to neuronal cell death, brain atrophy, and severe cognitive impairment.
Sleep abnormalities have long been known to be a feature of neurodegenerative disorders and in some cases are considered a core manifestation of the disease. Sleep has been shown to directly regulate the rate of Aβ production and clearance from the brain, and evidence suggests that sleep disruption may be a direct critical pathway by which Aβ disrupts hippocampal-dependent memory consolidation (Mander et al., 2015). Thus, improving sleep may directly support mnemonic processes and reduce the accumulation of Aβ, which is considered the pathogenic driver of AD.
Patients with AD also exhibit disruptions of daily (circadian) rhythms, but it is unclear whether this reflects a primary disorder of internal circadian timekeeping and whether disruption contributes to symptoms and progression. Circadian biology examines daily 24-hour (‘circa-diem’) rhythms that govern many aspects of physiology, behaviour and metabolism, including sleep-wake cycle, rest-activity patterns, cognitive function, mood, and many hormonal rhythms and metabolic processes. Changes in circadian rhythms may be a strong, reliable, and measurable indicator of the earliest signs of AD. Correction of circadian misalignment, including promotion of more stable and robust rhythms in cognition, sleep-wake, and metabolism, holds promise as an inexpensive and noninvasive method for slowing disease progression and improving quality of life for patients and their families.
To learn more, here is our recent review Kent et al., 2020.
Translational Neuroscience and Touchscreen Cognitive Testing
A huge challenge in developing treatments for Alzheimer’s disease is moving discoveries from fundamental, preclinical research into the clinical domain. This is referred to as the “translational gap.” One goal of my research is to shrink the translational gap by designing preclinical research that is directly informed by clinical research, and vice versa. My research utilizes the heightened control enabled by studying animal models to evaluate the cognitive processes most vulnerable to sleep and circadian rhythm disruption and then translate the insight gained from the rodent models to evaluate the same processes in humans. Touchscreen cognitive tests have been developed to increase the similarity between rodent and human testing, enabling greater control, precision, and translational potential.
Touchscreen testing in rodents enables the assessment of targeted cognitive domains comparable to test batteries used in humans, such as the Cambridge Neuropsychological Test Automated Battery (CANTAB), with the goal of having greater relevance to human health and disease. Touchscreen cognitive testing has numerous advantages compared to traditional tests of learning and memory. First, a battery approach can be taken, running a variety of operant tasks using the same testing chamber, which helps control for potential confounds (e.g., types of stimuli, rewards, apparatus). Second, the semi-automated approach enables several behavioural measures to be assessed simultaneously (e.g., accuracy, reaction time, activity counts, omission rates) and minimizes experimenter contact with animals during testing. Third, the precision and control enabled by the tasks, allows us to assess specific aspects of cognition and functions in targeted brain regions. Finally, touchscreen testing is ideal to combine with neurotechnology such as electrophysiology, chemogenetics, and optogenetics. Thus, touchscreen testing in rodents is highly translatable to humans and enables the mapping of complex behaviour onto specific aspects of neurobiology with the highest level of precision and control.
In addition to research, I am committed to advocating for change in the practice and communication of science. I have worked on initiatives trying to improve support for early career researchers and to make research more accessible, transparent, reproducible, and diverse. From 2014- 2019, I was an invited member of the eLife Early Career Advisory Group and was elected to Chair the group in 2017 and 2018. The advisory board helps guide the direction of the journal and the eLife initiative more broadly. In 2017, I helped organize the Future of Research Vancouver workshop, which developed recommendations for federal government policy changes that are needed to retain the most promising and skilled researchers in Canada (Clark et al., 2018, F1000). In 2019, I was appointed to the Governing Council of the Canadian Institutes of Health Research (CIHR).The CIHR Governing Council is responsible for developing the strategic directions and evaluating the overall performance of Canada’s publicly funded health research.
#ECRWednesday Webinar: Mental health support for early career researchers
#ECRWednesday Webinar: Organising and advocating for early career researchers
#ECRWednesday Webinar: Supporting preprints in the life sciences
#ECRWednesday Webinar: Private funding in the life sciences
#ECRWednesday Webinar: Graphic design tips for creating effective figures
Ratcliff, M., Rees, D., McGrady S., Bayliss, J., Kent, B. A., Bussey, T. J., Saksida, L. M., Howell, O. W., Morgan, A. H., Sun, Y, Andrews, Z. B.,Wells, T., Davies, J. S. (2019). Calorie restriction increases new adult born olfactory-bulb neurones in a ghrelin-dependent manner but acyl-ghrelin does not enhance sub-ventricular zone neurogenesis. Journal of Neuroendocrinology.
Kent, B. A., Michalik, M., Marchant, E. G., Yau, K. W., Feldman, H. H., Mistlberger, R. E., Nygaard, H. B. (2019). Delayed daily activity and reduced NREM slow wave power in the APP/PS1 mouse model of Alzheimer’s disease. Neurobiology of Aging.
Miranda, M., Kent, B. A., Morici, J. F., Gallo, F., Saksida, L. M., & Bussey, T. J., Weisstaub, N. V., Bekinschtein, P. (2018). NMDA receptors and BDNF are necessary for discrimination of overlapping spatial and non-spatial memories in perirhinal cortex and hippocampus. Neurobiology of Learning and Memory.
Nygaard, H. B., Omay, Z. E., Wu, S., Kent, B. A., Bernales, C. Q., Evans, D. M., Farrer, M., Vilarino-Guell, C., Strittmatter, S. M. (2018). Whole exome sequencing of an exceptional longevity cohort. Journal of Gerontology: Biological Sciences.
Kent, B. A., Heath, C., Kim, C-H., Ahrens, R., Fraser, P. E., St George-Hyslop, P., Bussey, T. J., & Saksida, L. M. (2018). Longitudinal evaluation of Tau-P301L transgenic mice reveals no impairment at 17 months of age. Brain and Behavior.
Miranda, M., Kent, B. A., Morici, J. F., Galo, F., Saksida, L. M., & Bussey, T. J., Weisstaub, N. V., Bekinschtein, P. (2017). Molecular mechanisms in perirhinal cortex selectively necessary for discrimination of overlapping memories, but independent of memory persistence. eNeuro.
Kent, B. A., Hvoslef-Eide, M., Saksida, L. M., & Bussey, T. J. (2016) The representational-hierarchical view of pattern separation: Not just hippocampus, not just space, not just memory? Neurobiology of Learning and Memory, 129, 99-106.
Nilsson, S. R. O., Celada, P., Fejgin, K., Thelin, J., Nielsen, J., Santana, N., Heath, C. J., Larsen, P. H., Nielsen, V., Kent, B. A., Robbins, T. W., Saksida, L. M., Bastlund, J. F., Bussey, T. J., Artigas, F., Didriksen, M. A. (2016). Mouse model of the 15q13.3 microdeletion syndrome shows prefrontal neurophysiological dysfunctions and associated attentional impairment. Psychopharmacology, 233(11), 2151-2163.
Nilsson, S. R. O., Fejgin, K., Gastambide, F., Vogt, M. A., Kent, B. A., Nielsen, V., Nielsen, J., Gass, P., Robbins, T. W., Saksida, L. M., Stensbal, T. B., Tricklebank, M. D., Didriksen, M., Bussey, T. J. (2016). Assessing the cognitive translational potential of a mouse model of the 22q11.2 microdeletion syndrome. Cerebral Cortex, 26(10), 3991-4003.
Kent, B. A., Oomen, C. A., Bekinschtein, P., Saksida, L. M., & Bussey, T. J. (2015). Cognitive enhancing effects of voluntary exercise, caloric restriction and environmental enrichment: a role for adult hippocampal neurogenesis and pattern separation? Current Opinion in Behavioral Sciences, 4, 179-185.
Kim, C. H., Heath, C. J., Kent, B. A., Bussey, T. J., & Saksida. L. M. (2015). The role of the dorsal hippocampus in two versions of the touchscreen automated paired associates learning (PAL) task for mice. Psychopharmacology, 232(21-22), 3899-3910.
Kent, B. A., Beynon, A. L., Hornsby, A. K., Bekinschtein, P., Bussey, T. J., Davies, J. S., Saksida, L. M. (2015). The orexigenic hormone acyl-ghrelin increases adult hippocampal neurogenesis and enhances pattern separation. Psychoneuroendocrinology, 51,431-439.
Green-Thompson, M. Z., Nixon, R. A., Saksida, L. M., Bussey, T. J., O’Kane, C., & Rubinsztein, D. C. (2014). Calpain inhibition mediates autophagy-dependent protection against polyglutamine toxicity. Cell Death and Differentiation, 433–444.
Oomen, C. A., Bekinschtein, P., Kent, B. A., Saksida, L. M., & Bussey, T. J. (2014). Adult hippocampal neurogenesis and its role in cognition. Wiley Interdisciplinary Reviews: Cognitive Science, 5(5), 573-587.
Bekinschtein, P.*, Kent, B. A.*, Oomen, C. A., Clemenson, G. D., Gage, F. H., Saksida, L. M., & Bussey, T. J. (2014). BDNF interacts with adult-born immature cells in the dentate gyrus during consolidation of overlapping memories. Hippocampus, 24(8), 905-911.
Bekinschtein, P., Kent, B. A., Oomen, C. A., Clemenson, G. D., Gage, F. H., Saksida, L. M., & Bussey, T. J. (2013). Consolidating unique memories: BDNF in the dentate gyrus is required for spatial pattern separation. Cell Reports, 5, 1-10.
Mar, A., Horner, A. E., Nilsson, S., Alsiö, J., Kent, B. A., Kim, C. H., Holmes, A., Saksida, L. M., Bussey, T. J (2013). The touchscreen operant platform for rodents: tests of executive function. Nature Protocols, 8, 1985-2005.
Horner, A. E., Heath, C. J., Hvoslef-Eide, M., Kent, B. A., Kim, C., Nilsson, S., Alsiö, J., Oomen, C. A., Holmes, A., Saksida, L. M., Bussey, T. J. (2013). The touchscreen operant platform for testing learning and memory in rats and mice. Nature Protocols, 8, 1961-1984.
Orr, P. T., Rubin, A. J., Fan, L., Kent, B. A., Frick, K. M. (2012). The progesterone-induced enhancement of object recognition memory consolidation involves activation of the extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR) pathways in the dorsal hippocampus. Hormones and Behavior, 61, 487-495.
Boulware, M. I., Kent, B. A., & Frick, K. M. (2011). The impact of age-related hormone loss on cognitive and neural function. In: Current Topics in Behavioral Neurosciences: Behavioral Neurobiology of Aging, Pardon, M. C., & Bondi, M. (Eds). Springer-Verlag:Berline-Hiedelberg.
Landry, G. J., Kent, B. A., Patton, D. F., Jaholkowski, M., Marchant, E. G., Mistlberger, R. E. (2011). Evidence for time-of-day dependent effect of neurotoxic dorsomedial hypothalamic lesions on food anticipatory circadian rhythms in rats. PLoS One, 6(9), e24187.
Thank you to the generous funding agencies that have made my research possible.
Available for consulting projects and mentorship. I have worked as an Education Consultant since 2012, helping students navigate applications to graduate schools in North America and Europe.