Fabian Fernandez

Fabian Fernandez

Assistant Professor, Psychology
Assistant Professor, Evelyn F Mcknight Brain Institute
Assistant Professor, Neurology
Assistant Professor, Neuroscience - GIDP
Assistant Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 621-7447

Work Summary

Work Summary

Fabian-Xosé Fernandez's work includes a focus on parsing the logic used by the circadian pacemaker to interpret multidimensional light patterns, developing light-emitting diode (LED) photo-stimulation protocols to improve mental and physical health across the lifespan, and understanding the role that nocturnal wakefulness plays in suicide risk and developing countermeasures centered around light exposure.

Research Interest

Fabian-Xosé Fernandez, PhD, Departments of Psychology and Neurology, McKnight Brain InstituteCircadian timekeeping is fundamental to human health. Unfortunately, under many clinical circumstances, the temporal organization of our minds and bodies can stray slowly from the Universal Time (UT) that is set with the Earth’s rotation. This disorganization has been linked to progression of several age-related and psychiatric diseases. Non-invasive phototherapy has the potential to improve disease outcomes, but the information that the brain’s clock tracks in twilight (or any electric light signal) to assure that a person entrains their sleep-wake cycles to the outside world is not understood. The central theme of my research program is to fill in this blank and to usher in an era where therapeutically relevant “high-precision” light administration protocols are institutionalized at the level of the American Medical and Psychiatric Associations to change the standard of care for a wide variety of conditions that impair quality of life. Of the conditions my lab is currently studying, we are particularly interested in how chronic and quick, sequenced light exposure can be designed to: 1. promote normal healthy aging and 2. strengthen adaptive cognitive/emotional responses to being awake in the middle of the night (12-6AM), a key interval of the 24-h cycle that we have associated with increased suicidal ideation and mortality. Our circadian work on suicide is done in very close partnership with the University of Arizona Sleep Health and Research Program directed by Dr. Michael A. Grandner.

Publications

Fernandez, F., & Reeves, R. H. (2015). Assessing cognitive improvement in people with Down syndrome: important considerations for drug-efficacy trials. Handbook of experimental pharmacology, 228, 335-80.

Experimental research over just the past decade has raised the possibility that learning deficits connected to Down syndrome (DS) might be effectively managed by medication. In the current chapter, we touch on some of the work that paved the way for these advances and discuss the challenges associated with translating them. In particular, we highlight sources of phenotypic variability in the DS population that are likely to impact performance assessments. Throughout, suggestions are made on how to detect meaningful changes in cognitive-adaptive function in people with DS during drug treatment. The importance of within-subjects evaluation is emphasized.

Fernandez, F., & Garner, C. C. (2007). Object recognition memory is conserved in Ts1Cje, a mouse model of Down syndrome. Neuroscience letters, 421(2), 137-41.

Ts1Cje and Ts65Dn are genetic mouse models of Down syndrome (DS). Like individuals with DS, these mice exhibit various hallmarks of hippocampal pathology, and deficits in hippocampal-based, declarative learning and memory tasks. Both spatial navigation and novel object recognition, two prototypical domains of declarative memory function, have been strongly characterized in the Ts65Dn DS model. Indeed, Ts65Dn mice show navigation problems in the Morris water maze, impaired alternation in a T-maze, and deficient working and reference memory in the radial arm maze task. They, likewise, show an inability to detect object novelty over time. In contrast to the Ts65Dn model, hippocampal-dependent cognition has been less well characterized in Ts1Cje. Although Ts1Cje mice have been found to exhibit spatial difficulties in the Morris water maze and reduced spontaneous alternation, their ability to process object-based information has never been examined. Here, we report that Ts1Cje mice perform normally in short-term and long-term novel object recognition tasks. The ability of Ts1Cje mice to detect object novelty, unlike Ts65Dn, may point to differences in the extent of hippocampal pathology in the two DS mouse models.

Fernandez, F., & Garner, C. C. (2007). Over-inhibition: a model for developmental intellectual disability. Trends in neurosciences, 30(10), 497-503.

Developmental intellectual disability (DID) is a daunting societal problem. Although tremendous progress has been made in defining the genetic causes of DID, therapeutic strategies remain limited. In particular, there is a marked absence of a unified approach to treating cognitive impairments associated with DID. Here, we suggest that the brain in many DID-related disorders is subject to a basic imbalance in neuronal activity, with an increased contribution of inhibition to neural circuits. This over-inhibition, in turn, is predicted to lead to deficits in synaptic plasticity and learning and memory. We further discuss possibilities for pharmacological intervention in DID, focusing on the concept of drug-induced 'therapeutic neuroadaptation' as a means of stably enhancing constitutive circuit excitability and cognition over time.

Fernandez, F., & Edgin, J. O. (2016). Pharmacotherapy in Down's syndrome: which way forward?. The Lancet. Neurology, 15(8), 776-7.
Fernandez, F., & Edgin, J. O. (2013). Poor Sleep as a Precursor to Cognitive Decline in Down Syndrome : A Hypothesis. Journal of Alzheimer's disease & Parkinsonism, 3(2), 124.

We propose that sleep disruption is a lever arm that influences how cognition emerges in development and then declines in response to Alzheimer disease in people with Down syndrome. Addressing sleep disruptions might be an overlooked way to improve cognitive outcomes in this population. This article is a contribution to a Special Issue on Down Syndrome curated by the editors of the Journal of Alzheimer's Disease & Parkinsonism.