Howard & Brumback Study How Brain Circuit Processing Is Altered in Neurodevelopmental Disorders

Work by Mulva husband-and-wife researchers MacKenzie Howard, PhD, an assistant professor of neurology and neuroscience, and Audrey Brumback, MD, PhD, an assistant professor of neurology, focuses on understanding neurodevelopmental disorders at the cellular and molecular levels. By defining how different brain circuits process information and how that information processing is altered in neurodevelopmental disorders, their team hopes to uncover new ways of shifting brain cell activity from the disordered processing back toward the normal state.

In two recently published articles, the team defined differences between two separate subcircuits within the connections between the prefrontal cortex and the mediodorsal thalamus, a processing network involved in controlling higher functions such as cognition, learning, and social behavior. Different properties of neurons in the thalamic subregions shift the timing of cell responses, changing the type of information these two different circuits extract (Lyuboslavsky et al. 2024). They next studied a genetically engineered mouse model of fragile X syndrome. In these animals, brain cells in one of the subcircuits are altered while those in the other subcircuit are not (Ordemann et al. 2025). This vital work is improving our understanding of how and where such disorders take root and may facilitate the development of future therapies.

Further work by the Brumback–Howard team has explored the roots of neurodevelopmental disorders in brain areas that are often overlooked. The cerebellum has long been known for its role in coordinating and learning movements, but its role in learning and memory, cognition, social behavior, and language is less well known. The team studied a genetically engineered mouse model of Dravet syndrome, which typically causes severe epilepsy, disabling movement disorders, developmental and intellectual regression, and autism. They discovered that while the seizures associated with Dravet syndrome likely arise in the cortex and hippocampus, many of its other manifestations may arise from altered neural activity in the cerebellum (Guillén et al. 2025). These findings may shift and guide the priorities for therapy development to focus on the cerebellum and other brain structures that are rarely considered in neurodevelopmental disorders.

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