Rhythmic changes in sex hormone levels across the ovarian cycle exert powerful effects on the brain and behavior, and confer female-specific risks for neuropsychiatric conditions. In this talk, Dr. Kundakovic will discuss the role of fluctuating ovarian hormones as a critical biological factor contributing to the increased depression and anxiety risk in women. Cycling ovarian hormones drive brain and behavioral plasticity in both humans and rodents, and the talk will focus on animal studies in Dr. Kundakovic’s lab that are revealing the molecular and receptor mechanisms that underlie this female-specific brain dynamic. She will highlight the lab’s discovery of sex hormone-driven epigenetic mechanisms, namely chromatin accessibility and 3D genome changes, that dynamically regulate neuronal gene expression and brain plasticity but may also prime the (epi)genome for psychopathology. She will then describe functional studies, including hormone replacement experiments and the overexpression of an estrous cycle stage-dependent transcription factor, which provide the causal link(s) between hormone-driven chromatin dynamics and sex-specific anxiety behavior. Dr. Kundakovic will also highlight an unconventional role that chromatin dynamics may have in regulating neuronal function across the ovarian cycle, including in sex hormone-driven X chromosome plasticity and hormonally-induced epigenetic priming. In summary, these studies provide a molecular framework to understand ovarian hormone-driven brain plasticity and increased female risk for anxiety and depression, opening new avenues for sex- and gender-informed treatments for brain disorders.

Cognitive neuroscience has witnessed great progress since modern neuroimaging embraced an open science framework, with the adoption of shared principles (Wilkinson et al., 2016), standards (Gorgolewski et al., 2016), and ontologies (Poldrack et al., 2011), as well as practices of meta-analysis (Yarkoni et al., 2011; Dockès et al., 2020) and data sharing (Gorgolewski et al., 2015). However, while functional neuroimaging data provide correlational maps between cognitive functions and activated brain regions, its usefulness in determining causal link between specific brain regions and given behaviors or functions is disputed (Weber et al., 2010; Siddiqiet al 2022). On the contrary, neuropsychological data enable causal inference, highlighting critical neural substrates and opening a unique window into the inner workings of the brain (Price, 2018). Unfortunately, the adoption of Open Science practices in clinical settings is hampered by several ethical, technical, economic, and political barriers, and as a result, open platforms enabling access to and sharing clinical (meta)data are scarce (e.g., Larivière et al., 2021). We are working with clinicians, neuroimagers, and software developers to develop an open source platform for the storage, sharing, synthesis and meta-analysis of human clinical data to the service of the clinical and cognitive neuroscience community so that the future of neuropsychology can be transdiagnostic, open, and FAIR. We call it neurocausal (https://neurocausal.github.io).

In highly volatile environments, performing actions that address current needs and desires is an ongoing challenge for living organisms. For example, the predictive value of environmental signals needs to be updated when predicted and actual outcomes differ. Furthermore, organisms also need to gain control over the environment through actions that are expected to produce specific outcomes. The data to be presented will show that these processes are highly reliant on thalamocortical circuits wherein thalamic nuclei make a critical contribution to adaptive decision-making, challenging the view that the thalamus only acts as a relay station for the cortical stage. Over the past few years, our work has highlighted the specific contribution of multiple thalamic nuclei in the ability to update the predictive link between events or the causal link between actions and their outcomes via the combination of targeted thalamic interventions (lesion, chemogenetics, disconnections) with behavioral procedures rooted in experimental psychology. We argue that several features of thalamocortical architecture are consistent with a prominent role for thalamic nuclei in shaping mental representations.

Are the immune system, brain, mind and mood related? Could this explain why chronic low-grade peripheral inflammation is also noted in approximately 1/3 of those with major depressive disorder (MDD)? The field recognized today as immunopsychiatry was founded on scientific evidence that germinated over 30 years ago. Since, it has been understood that (i) there could be a causal link between inflammation and depression, (ii) select blood immune markers show robust potential as biomarkers for inflammation-linked depression, and more generally, (iii) Descartes' theories on mind-body dualism were biologically erroneous. Nonetheless, the mechanistic brain-immune axis in the trinity formulating inflammation-linked depression i.e. psycho-neuro-immunology, still remains unclear. This talk will discuss findings from our recent investigation endeavored to unpack this by linking functional connectivity abnormalities with peripheral immune markers.