Description
- Abstract:
- Objective: Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technique with established clinical applications, but heterogeneous treatment outcomes. An incomplete understanding of how stimulation translates into neural effects limits its therapeutic potential. This thesis investigates whether TMS pulse parameters can be selected to shift the relative recruitment of different cortical cell type populations, a phenomenon termed cell-type targeting, as a step toward principled, mechanism-based treatment design. Methods: A computational neural modeling framework developed across previous studies was adapted and extended to characterize cell-type targeting across pulse conditions. Simulations were run across 84 morphologically and biophysically realistic compartmental cell models spanning three cortical cell types (L2/3 pyramidal cells [L2/3PCs], L4 large basket cells [L4LBCs], and L5 pyramidal cells [L5PCs]) across three pulse shapes (monophasic, half-sine, biphasic) and five pulse widths (18.75 to 300 μs). Threshold maps characterizing the cells’ excitabilities were used to derive population-level recruitment curves, and compared across conditions using a targeting metric quantifying differential recruitment. Bootstrap confidence intervals characterized the variability of targeting predictions given the finite morphology sample. Results: Pulse width was the dominant driver of cell-type targeting. Longer widths preferentially recruited L2/3PCs over L5PCs and L4LBCs compared to shorter pulse widths, while shorter widths tended to target L4LBCs over pyramidal cell types. These effects were statistically robust across a wide range of pulse width comparisons, particularly those involving L2/3PCs. Pulse shape contributed secondary targeting effects, smaller and less consistent than those of pulse width. Targeting differences between L4LBCs and L5PCs were generally small. Conclusions: TMS pulse parameters, particularly pulse width, produce systematic and statistically reliable shifts in the relative recruitment of cortical cell type populations in this modeling framework. These findings provide a predictive computational foundation for rational pulse design for controlling the pattern of cell-type-specific activation produced by TMS, and motivate experimental validation and extension to circuit- and network-level models as steps toward mechanistically grounded treatment optimization.
- Notes:
- Thesis (Sc. M.)--Brown University, 2026
Citation
Tajchman, Jacob,
"Computational Modeling of Neural Cell-Type Targeting with Transcranial Magnetic Stimulation"
(2026).
Biomedical Engineering Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:9cgyxery/
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Biomedical Engineering Theses and Dissertations
Theses and Dissertations for the Biomedical Engineering department....