Research

We have three main projects in the lab that stem from interrelated lines of research and use a variety of neuropathological, molecular, tract-tracing, high-resolution microscopy, imaging, and computational approaches.

1. Networks for flexible behavior and attention in the thalamus, amygdala, and cortex
2. Comparative studies of brain networks in non-human primates and humans: a template for study of disorders
3. Neuropathology of Autism Spectrum Disorders

Networks for flexible behavior and attention in the thalamus, amygdala, and cortex

We study brain pathways and complex circuit interactions in networks linking prefrontal cortices, the amygdala, and the thalamus in non-human primates. These circuits underlie brain activity shifts that direct attention for flexible behavior. One emerging theme from this continuing work is the increased role of interactions between excitatory cortical and subcortical pathways with purely inhibitory systems in the thalamic reticular nucleus (TRN), and the intercalated masses in the amygdala (IM). Another major focus of our current research is to further study specialized excitatory-inhibitory interactions in the primate brain and investigate how cortical pathways interact with high-order thalamic nuclei for flexible behavior. We study distinct cell type and synaptic interactions in each node of these circuits, using tract-tracing, cutting-edge, high-resolution imaging and large-scale 3D-reconstruction analysis. Experimental approaches are complemented by computational modeling to simulate network function and dysfunction in psychiatric diseases.

Comparative studies of brain networks in non-human primates and humans: a template for study of disorders

A major focus of our work revolves around an important unanswered question: Can the wealth of information on the structure and connections of the brain, derived from animal studies, be translated to understand neural communication in humans and disruption in brain diseases? Our goal is to use high-resolution approaches to identify similarities and key differences in cellular, synaptic, and molecular features of cortical and subcortical networks in humans and non-human primates. The aim is to develop reliable templates to translate high-resolution data on connections and circuit interactions from non-human primates and other mammals to humans, through side-by-side study of the structure and connections in these species at multiple scales. Our ongoing work is increasingly focusing on linking (epi)genetics with the anatomical and functional organization of corticocortical and thalamocortical pathways. The aim is to facilitate study of complex disorders through a novel framework that can be used to predict connections in humans, where invasive connectivity studies are precluded.

Neuropathology of Autism Spectrum Disorders

Using the template described above, we study the development of underlying pathology in functionally distinct feedforward, feedback, short-, or long-range brain pathways in individuals with autism spectrum disorders. For our neuropathological studies we use donated post-mortem brain tissue from adults and children. We model networks that have a role in directing attention, through thalamus and frontal cortex, to mediate social interactions and modulate emotional responses. We use circuit data and modeling to test hypotheses about mechanisms of disruption in neural communication at the level of cells, synapses and the larger system. We additionally link (epi)genetics with cellular processes and network disruption to elucidate the development of autism and inform potential interventions. We are also probing distinct disruptions in frontal-thalamic networks that are consistently affected in autism along with comorbid disorders, including depression, anxiety, schizophrenia, and epilepsy.