Neuroscience research has largely focused on the microscale of neurons and molecular biology or the macroscale of brain regions and networks. However, the organizational principles in between these two extremes at the mesoscale are the critical determinants of brain function (and dysfunction). For example, the layered organization of neurons in the cerebral cortex determines information processing capabilities, and variations in this layered organization determines functional localization throughout the brain. However, technological limitations, that is, the need to see tiny structures across vast areas, have limited our understanding of mesoscale neuroanatomy and the contributions of the mesoscale to neurodevelopment and neurodegenerative disease.
Dr. Koscik’s research is focused on understanding mesoscale neuroanatomy, using ultra-high-resolution neuroimaging in postmortem human brains. While typical neuroimaging research explores resolution of 1 mm3, studying the laminar architecture of the cerebral cortex requires whole brain imaging approximately 300 to 1,000 times more detailed around 150 microns. Dr. Koscik’s team is combining advances in scan acquisition, image processing, and deep learning technologies to explore mesoscale neuroanatomy in higher detail and with higher throughput than previously possible. The ultimate goal of this research is to provide novel insight into mesoscale neuroanatomical features, such as cortical laminar architecture, that simultaneously provide us with our fantastic abilities as humans, but where subtle perturbations may contribute to neurological, psychiatric, and neurodegenerative disease.
In line with this idea, emerging evidence suggests that maladaptive development of the cortical lamina may drive the pathology of Huntington’s disease (HD). Early in HD, neurons fail to migrate into normal laminar patterns in the cortex, resulting in hyperexcitability in cortical circuits. Through a subsequent cascade of events this hyperexcitability may cause downstream neurodegeneration through excitotoxic pathways. A goal of Dr. Koscik’s current research is to explore maladaptive laminar development in HD and explore how this mediates HD pathology. Ultimately, a better understanding of the cascading, neurodevelopmental, pathological mechanisms in HD will provide the knowledge necessary to guide therapeutic agents to appropriate neuroanatomical targets and to deliver these therapeutics to developmental stages that are appropriate for rectifying the underlying pathology.