Current Topics of Research in the Lab Include 

a) How early-life adversity/stress provokes anhedonia, and the underlying perturbations of the maturation of reward/pleasure circuitry.

b) How early-life adversity/stress provokes spatial memory deficits and the transcriptional / epigenomic mechanisms that re-program hippocampal neurons and circuits

c) How prolonged early-life seizures, especially those associated with fever, disrupt the maturation of hippocampal circuits and memory processes

d) Intra-individual methylomics in rodents and humans as predictive biomarkers of early-life adversity-induced cognitive and emotional problems

e) How multiple concurrent acute stresses, such as occur in mass shootings and natural disasters, impact memory processes in males and females.

Tallie Z. Baram

Tallie Z. Baram, MD, PhD is the Danette Shepard, Bren and distinguished professor at UCI School of Medicine. She is a developmental neuroscientist and child neurologist who has focused her research efforts on the influence of early-life experiences on brain maturation and the underlying mechanisms. Throughout her career, Baram has studied this topic in two broad contexts, pertaining, respectively, to stress-related and activity-dependent plasticity: a) How early-life experiences including adversity/stress promote enduring vulnerability to cognitive and emotional disorders; and b) how early-life seizures, especially those associated with fever, can convert a normal brain into an epileptic one.

A common thread of Baram’s research program is the use of multiple and trans-disciplinary technologies and levels of analysis including molecular, cellular and circuit methods and cross-species studies. She employed these to uncover how adverse early-life experiences sculpt memory-, stress- and reward-related circuit maturation. In this context, she has uncovered novel types of adversity in humans and rodents (unpredictable sequences of sensory signals) that contributes to aberrant circuit maturation (e.g., Birnie & Baram, Science, 2022). Additionally, she has focused on the overarching hypothesis that neuronal populations and projections expressing the stress-related peptide CRH may be particularly vulnerable to early-life adversity, resulting in disrupted operations of networks that include them. This notion has led to identification of novel CRH+ reward-circuit projections, and assessments of established CRH-cell populations using single-cell transcriptomics.

The Baram lab has pioneered naturalistic, translationally-relevant paradigms of early-life adversity (ELA) that have been embraced world-wide, and demonstrated the causal influence of ELA on cognitive and emotional health via convergent actions of multiple mediators (including locally-synthesized CRH). More recently, through collaborative work in her NIH funded Conte Center and a recent collaborative award with CHOC from the California Initiative to Advance Precision Medicine, she is translating her discoveries back to the clinic. Her work has been published in leading journals (e.g., Science, Nature Rev Neurosci, Nature Medicine, Nature Neurosci) and cited over 30,000 times (H = 96, google scholar). Baram’s discoveries have been universally recognized, apparent from awards including the NIH NINDS Javits Merit Award, premier Research Awards of the AES (2005), CNS (2013), ANA (2014) and AAN (2018), and a Public Impact Award (CNLM, 2022). 

Baram strives to contribute to the scientific community by, for examples, chairing NIH study sections and involvement in editorial boards and professional organizations, including ACNP. She is passionate and committed to mentoring, with emphasis on scientific rigor and inclusivity: Baram is PI of one of only two NIH-funded T32s focused on Epilepsy, and mentor of several recent K99 and F30 awardees. Many of her trainees, from diverse racial and geographical backgrounds are now contributing independently and successfully to our understanding of the brain in health and disease.

Lab News: 

MAY 2024 | In this collaboration, researchers sought to develop a diagnostic tool for anhedonia assessment in infancy. They created an assessment instrument for anhedonia/reward processing in infancy, the Infant Hedonic/Anhedonic Processing Index (HAPI-Infant), which is suitable for recognizing anhedonia during the first year of life with strong predictive value for later depressive symptoms. This paper is available in J Affect Disord: Infant hedonic/anhedonic processing index (HAPI-Infant): assessing infant anhedonia and its prospective association with adolescent depressive symptoms (link to paper).

FEBRUARY 2024 | In this collaboration, researchers conducted a novel investigation of unpredictable maternal sensory signals in early life and child internalizing behaviors. Finding across three diverse cohorts suggests that unpredictable maternal signals early in life shape the development of internalizing behaviors, particularly fearfulness and anxiety. This paper is available in J Affect Disord: Across ages and places: unpredictability of maternal sensory signals and child internalizing behaviors (link to paper).

In this prospective longitudinal study, child-mother pairs were assessed for maternal negative mood level and entropy. Later, adolescents engaged in a fMRI task acquired between two resting-state scans. They found prenatal maternal mood entropy, but not mood level, was associated with salience network integrity. These findings suggest that fetal exposure to maternal mood dysregulation is associated with a weakened and inflexible salience network. This paper is available in Biol Psychaitry Cogn Neurosci Neuroimaging: Prenatal exposure to maternal mood entropy is associated with a weakened and inflexible salience network in adolescence (link to paper).

DECEMBER 2023 | Annabel, Ryan and Noriko examined the relation of several dimensions of early-life adversity (ELA) to changes of DNA methylation, using a longitudinal within-subject design and a high threshold for methylation changes. These findings establish longitudinal, within-subject changes in methylation profiles as a signature of some types of ELA in an individual child. Notably, such changes are detectable beyond the age-associated DNA methylation dynamics. This paper is available in bioRxiv: Within-subject changes in methylome profile identify individual signatures of early-life adversity, with a potential to predict neuropsychiatric outcome (link to paper).

Congratulations to Saibrinda and Brinda for being awarded a UROP fellowship for their project “Investigating the Impact of Acute Traumatic Stress on Stress-Related Memories and Avoidance Behavior in Mice” under the supervision of Rachael and Dr. Baram!

Congratulations to Neeraj for being awarded a UROP fellowship for his project “Impact of Early-Life Adversity on Positive Operant Conditioned Reward Motivated Behavior” under the supervision of Cassie and Dr. Baram!

OCTOBER 2023 | In their paper, Cassie, Dr. Chen and Matt describe the robust and specific activation of the paraventricular thalamus (PVT) during early-life adversity (ELA). They find that the PVT is the only brain region analyzed that distinguishes ELA and typically-reared groups in terms of neuronal activation. Their work points to an important role for the PVT in encoding emotionally salient experiences early in life and mediating their impacts in adulthood. This paper is available in Biol Psychiatry Glob Open Sci: Genetic tagging uncovers a robust, selective activation of the thalamic paraventricular nucleus by adverse experiences early in life (link to paper).

AUGUST 2023 | Congratulations to Dr. Chen, along with Dr. Mahler and Dr. Baram, for receiving an NIH R01 grant!

JUNE 2023 | Congratulations to Amalia for being awarded a Postdoc.Mobility Fellowship by the Swiss National Science Foundation!