Spotlight on: Professor Josselin Houenou and the MODE-BD Team
Learn more about the Multi-scale Oscillations, Dynamics & Emotion in Bipolar Disorder (MODE-BD) Team and research.
Redefining Bipolar Disorder as a Dynamical Disease
For patients and clinicians alike, the reality of bipolar disorder is defined by change, instability, and cyclicity. The MODE-BD (Multi-scale Oscillations, Dynamics & Emotion in Bipolar Disorder) team, based at the Department of Psychiatry, University of Melbourne and at the Northern Hospital, is dedicated to shifting the research paradigm from describing symptoms to understanding the fundamental mechanisms of this instability. We operate on the premise that bipolar disorder is not merely a deficit in mood regulation, but a systemic failure of temporal adaptation. Our mission is to bridge the "explanatory gap" that currently exists between our understanding of neuronal abnormalities occurring in bipolar disorder and the observable behavioral cycles of mania and depression.
Bridging the Gap, A Multi-Scale Approach
Current research in bipolar disorder is often siloed, with geneticists studying ion channels, imaging scientists studying circuits, and clinicians studying circadian rhythms and mood swings, but rarely connecting these different scales. The MODE-BD team is designed to address this multi-scale challenge. We investigate how microscopic biological abnormalities—such as defects in calcium signaling—can scale up to affect neural circuits, eventually emerging as the macroscopic fluctuations in energy, sleep, emotion and mood that characterize the disorder. By linking these distinct levels of observation, from the neuron to human behavior, we aim to construct a unified, biologically grounded model of how the bipolar brain functions and malfunctions over time.
The Mechanistic Core: Homeostasis and Dynamical Systems
At the heart of our research is the Homeostatic Dysregulation of Bipolar Disorder (HDBD) model. We utilise Dynamical Systems Theory to mathematically model the brain as a complex system that strives for equilibrium. Our working hypothesis is that Bipolar Disorder represents a fragility in homeostatic regulation—a "broken thermostat." We investigate how failures in neuronal homeostasis (the brain's ability to reset excitability, often occurring during sleep) lead to a loss of resilience. Using concepts like attractors (stable states), bifurcations (tipping points), and criticality (the edge of chaos), we simulate how a brain can become "stably unstable," getting stuck in deep depressive states or spiraling into the self-reinforcing momentum of mania.
Validating Theory with Real-World Data
To ensure our theoretical models reflect clinical reality, MODE-BD employs rigorous validation strategies using "Long Phenotyping." We move beyond single-snapshot assessments to capture the dynamic trajectory of the illness. By combining longitudinal neuroimaging (high-field MRI, EEG) with high-frequency monitoring of sleep, activity, and mood, we seek to observe the mathematical “liability." This allows us to test whether specific dynamical markers—such as Critical Slowing Down (a mathematical sign of imminent collapse)—can be detected in patient data before a relapse occurs, validating the HDBD model in a clinical setting.
The MODE-BD team benefits from a strong clinical partnership between the Department of Psychiatry at the University of Melbourne and the Mental Health Services at Northern Health, that grounds our high-level modeling in patient care. We provide a unique interdisciplinary environment for PhD students and researchers who are eager to combine computational neuroscience, biophysics, neuroimaging and clinical psychiatry. By deciphering the laws of motion that govern bipolar cycles, MODE-BD aims to transform our fundamental understanding of the disorder, paving the way for interventions that target the dynamics of the illness rather than just its symptoms.