Abstract Objective. Decades ago, neurosurgeons used electrical impedance measurements in the brain for coarse intraoperative tissue differentiation. Over time, these techniques were largely replaced by more refined imaging and electrophysiological localization. Today, advanced methods of diffusion tensor imaging (DTI) and finite element method (FEM) modeling may permit non-invasive, high-resolution intracerebral impedance prediction. However, expectations for tissue-impedance relationships and experimentally verified parameters for impedance modeling in human brains are lacking. This study seeks to address this need. Approach. We used FEM to simulate high-resolution single- and dual-electrode impedance measurements along linear electrode trajectories through (1) canonical gray and white matter tissue models, and (2) selected anatomic structures within whole-brain patient DTI-based models. We then compared intraoperative impedance measurements taken at known locations along deep brain stimulation (DBS) surgical trajectories with model predictions to evaluate model accuracy and refine model parameters. Main results. In DTI-FEM models, single- and dual-electrode configurations performed similarly. While only dual-electrode configurations were sensitive to white matter fiber orientation, other influences on impedance, such as white matter density, enabled single-electrode impedance measurements to display significant spatial variation even within purely white matter structures. We compared 308 intraoperative single-electrode impedance measurements in five DBS patients to DTI-FEM predictions at one-to-one corresponding locations. After calibration of model coefficients to these data, predicted impedances reliably estimated intraoperative measurements in all patients (R=0.784±0.116, n=5). Through this study, we derived an updated value for the slope coefficient of the DTI conductance model published by Tuch et al., k=0.0649 S·s/mm3 (original k=0.844), for use specifically in humans at physiological frequencies. Significance. This is the first study to compare impedance estimates from imaging-based models of human brain tissue to experimental measurements at the same locations in vivo. Accurate, non-invasive, imaging-based impedance prediction has numerous applications in functional neurosurgery, including tissue mapping, intraoperative electrode localization, and DBS.