Modeling non-invasive brain stimulation, particularly transcranial magnetic stimulation (TMS) of the primary motor cortex (M1), has been previously explored through simulation methods at different scales. However, the coupling of TMS induced electric fields to neural mass models is still largely unexplored, while previously approached as an arbitrary current pulse [1, 2]. Via multi-scale simulations at the subcellular and neural mass level we study the underlying mechanisms of electromagnetic activation of cortical tissue by TMS. Validation of the coupling model is aided by measurements like EMG of muscle activation [3], EEG [4], and invasive recordings of so-called DI-waves on the spinal cord following TMS [3]. The model architecture is defined by choosing the cell morphologies, electric fields, connectivity, and cortical circuitry that describes the desired system. The methods developed here lay the groundwork for studying the effects of electromagnetic stimulation on any circuit architecture and facilitate realistically motivated coupling between electric fields and mean field state variables. The TMS response of M1 is characterized by corticospinal pyramidal tract axons originating from deep layer 5 (L5) carrying direct (D-) and indirect (I-) waves. D-waves are believed to be generated by direct stimulation of L5 axons, while I-waves may stem from indirect activation of L5 cells from presynaptic cells [3]. This study focuses on the generation of I-waves from cortical activity. Using reconstructed compartment models of neuron morphologies we simulate spatiotemporal dynamics on cortical axons in response to TMS induced electric fields. Generated action potentials propagate through the axonal arbor to axon terminals, forming synapses to other cells. The postsynaptic potential and thereby the intracellular current is governed by synaptic and dendritic dynamics. The resulting current entering L5 somata, averaged over cells, defines the current inputs to a neural mass model governing the firing rate of a L5 population. The L5 population’s mean firing rate is proportional to the average cortical output that projects to the spinal cord and is qualitatively comparable to I-wave measurements. We validate the coupling model against the measured I-waves and explore directional sensitivity and dose dependence of cortical activation as driven by the underlying biophysics and stimulation paradigm.