Multi-scale modeling to investigate the effects of transcranial magnetic stimulation on morphologically-realistic neuron with depression

Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique to activate or inhibit the activity of neurons, and thereby regulate their excitability. This technique has demonstrated potential in the treatment of neuropsychiatric disorders, such as depression. However, the effect of TMS on neurons with different severity of depression is still unclear, limiting the development of efficient and personalized clinical application parameters. In this study, a multi-scale computational model was developed to investigate and quantify the differences in neuronal responses to TMS with different degrees of depression. The microscale neuronal models we constructed represent the hippocampal CA1 region in rats under normal conditions and with varying severities of depression (mild, moderate, and major depressive disorder). These models were then coupled to a macroscopic TMS-induced E-Fields model of a rat head comprising multiple types of tissue. Our results demonstrate alterations in neuronal membrane potential and calcium concentration across varying levels of depression severity. As depression severity increases, the peak membrane potential and polarization degree of neuronal soma and dendrites gradually decline, while the peak calcium concentration decreases and the peak arrival time prolongs. Concurrently, the electric fields thresholds and amplification coefficient gradually rise, indicating an increasing difficulty in activating neurons with depression. This study offers novel insights into the mechanisms of magnetic stimulation in depression treatment using multi-scale computational models. It underscores the importance of considering depression severity in treatment strategies, promising to optimize TMS therapeutic approaches.