He directs the Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), a partnership between Georgia State University, Georgia Institute of Technology, and Emory University, and holds faculty appointments at all three institutions.

He was formerly the President of the Mind Research Network and a Distinguished Professor of Electrical and Computer Engineering at the University of New Mexico.

He is the creator of the group independent component analysis algorithm,[2] which has become widely used for extracting 'networks' of coherent activity from functional magnetic resonance imaging (fMRI) data.

[3] He has also developed techniques to link many different types of data, called 'data fusion' including various types of brain imaging (structural, functional, connectivity) with genomic and epigenomic data.

[4] A key focus of Calhoun's work is the development of tool to identify brain imaging markers to help identify and potentially treat various brain disorders including schizophrenia, bipolar disorder, autism, Alzheimer's disease, and many more.