The posteromedial cortex is a brain region that is especially abnormal in many psychiatric diseases, including depression, schizophrenia, and anxiety. However, it has traditionally received little attention from neuroscientists, in part because we do not understand its underlying biology. We propose to remedy this problem by uncovering posteromedial cortical circuits using tract-tracing in nonhuman primates and diffusion- weighted magnetic resonance imaging in nonhuman primates and humans. This pipeline will allow us to create a segmentation of the posteromedial cortex according to its anatomical connectivity. First, we propose to tile the nonhuman primate posteromedial cortex with tract-tracer injections, which will allow us to analyze its connectivity with other, better-understood brain regions. We will use these data to segment the posteromedial cortex according to its anatomical connectivity. We expect that different segments will connect with distinct, well-defined networks within the brain. Next, we will collect diffusion-weighted neuroimaging data in nonhuman primates and humans. Although this method allows noninvasive detection of some connections, it is highly susceptible to errors. We will use the principles of white matter organization identified in the tract-tracing data to guide and debug these neuroimaging data. Because tract-tracing cannot be performed in humans, this pipeline offers a rare possibility to infer anatomical connectivity in the human brain. Finally, based on prior neuroimaging experiments, scientists have hypothesized that the posteromedial cortex may connect with a particularly large number of brain regions and networks. Thus, we would like to determine the extent of axonal collateralization in the neurons of this brain region. In other words, does a single posteromedial cortical neuron project to many other brain regions, or are the circuits largely separate? Together, we expect these projects will elucidate PMC anatomical connectivity in such a way that large-scale neuroimaging networks can be linked with specific neuronal circuits.
This research aims to delineate the circuits of a particular brain area, the posteromedial cortex, that is highly abnormal in mental illness, but has received little attention. We will use anatomical tract-tracing and neuroimaging to uncover the connectivity patterns of this brain region. This work can be used to link particular mental illnesses with disruptions of specific connections, and will ultimately highlight new targets for neuromodulatory interventions.
