Neuroscience is undergoing a revolution in the quality and quantity of available data. Our challenge is to turn this exquisite new data into a more complete understanding of how the brain works, and to translate that knowledge into meaningful change for patients with brain disorders.
I apply tools from mathematics and neuroscience to study how memories are stored across the brain, and how this process breaks down in people with memory problems (like some patients with psychiatric disorders or brain damage).
I develop mathematical models of how higher cognitive functions such as short and long-term memories emerge from the interactions between cells across the brain. I collaborate with anatomists, physiologists and psychiatrists in order make our models accurately reflect the cutting edge of neuroscience knowledge while staying relevant and useful for clinicians.
PhD in Neuroimaging, 2015
King's College London (Institute of Psychiatry)
MSc in Neuroscience, 2010
King's College London (Institute of Psychiatry)
BA (hons) in Mathematics, 2009
Trinity College Dublin
A growing body of evidence suggests that conscious perception of a sensory stimulus triggers an all-or-none activity across multiple cortical areas, a phenomenon called ‘ignition’. In contrast, the same stimulus, when undetected, induces only transient activity. In this work, we report a large-scale model of the macaque cortex based on recently quantified structural connectome data. We use this model to simulate a detection task, and demonstrate how a dynamical bifurcation mechanism produces ignition-like events in the model network. Within this framework, the model predicts that feedforward excitatory transmission is primarily mediated by the fast AMPA receptors to ensure rapid signal propagation from sensory to associative areas. In contrast, a large fraction of the inter-areal feedback projections and local recurrent excitation depend on the slow NMDA receptors, to ensure ignition of distributed frontoparietal activity. Our model predicts, counterintuitively, that fast-responding sensory areas contain a higher ratio of NMDA to AMPA receptors compared to association cortical areas that show slow, sustained activity. We validate this prediction using in-vitro receptor autoradiography data. Finally, we show how this model can account for various behavioral and physiological effects linked to consciousness. Together, these findings clarify the neurophysiological mechanisms of conscious access in the primate cortex and support the concept that gradients of receptor densities along the cortical hierarchy contribute to distributed cognitive functions.
Dopamine is required for working memory, but how it modulates the large-scale cortex is unknown. Here, we report that dopamine receptor density per neuron, measured by autoradiography, displays a macroscopic gradient along the macaque cortical hierarchy. This gradient is incorporated in a connectome-based large-scale cortex model endowed with multiple neuron types. The model captures an inverted U-shaped dependence of working memory on dopamine and spatial patterns of persistent activity observed in over 90 experimental studies. Moreover, we show that dopamine is crucial for filtering out irrelevant stimuli by enhancing inhibition from dendrite-targeting interneurons. Our model revealed that an activity-silent memory trace can be realized by facilitation of inter-areal connections and that adjusting cortical dopamine induces a switch from this internal memory state to distributed persistent activity. Our work represents a cross-level understanding from molecules and cell types to recurrent circuit dynamics underlying a core cognitive function distributed across the primate cortex.
Dynamics and functions of neural circuits depend on synaptic interactions mediated by receptors. Therefore, a comprehensive map of receptor organization is needed to understand how different functions may emerge across distinct cortical regions. Here we use in-vitro receptor autoradiography to measure the density of 14 neurotransmitter receptor types in 109 areas of macaque cortex. We integrate the receptor data with other anatomical, genetic and functional connectivity data into a common cortical space. We uncovered a principal gradient of increasing receptor expression per neuron aligned with cortical hierarchy from early sensory cortex to higher cognitive areas. A second gradient, primarily driven by 5-HT1A receptors, peaks in the anterior and subcallosal cingulate, suggesting that the macaque may be a promising animal model for major depressive disorder. The receptor gradients may enable rapid, reliable information processing in sensory cortical areas and slow, flexible integration of information in higher cognitive areas.