A novel interleaved TMS-MRS approach with standard MRI hardware

Interleaved TMS-fMRI has advanced understanding of network modulation but is limited to hemodynamic measures. We introduce a novel interleaved TMS-MRS platform, using standard MRI hardware, to assess real-time neurochemical changes and demonstrate feasibility in a clinical sample of patients with treatment-resistant depression (TRD).

Nine TRD participants (mean age 47.3 ± 13.9) underwent interleaved TMS-MRS on a 3T Siemens Prisma. A 20 mm³ voxel was placed over individualized left dlPFC targets. ¹H-MRS spectra were acquired at baseline and during 10 Hz burst stimulation. Spectral quality and metabolite concentrations were compared across conditions.

Spectral quality was preserved across conditions (FWHM baseline: 0.041 ± 0.005; active: 0.040 ± 0.005; p = 0.699) and signal-to-noise remained stable (baseline: 38.29 ± 5.38; active: 34.67 ± 9.12; p = 0.790). Two metabolites differed significantly: alanine increased during stimulation (0.58 ± 0.16 vs. 0.46 ± 0.14; p = 0.031), while NAA + NAAG decreased (9.07 ± 2.02 vs. 8.83 ± 0.99; p = 0.031). Exploratory analyses suggested associations between baseline and stimulation-induced metabolites (e.g., GSH, GABA, lactate) and clinical improvement following accelerated iTBS.

Interleaved TMS-MRS is feasible with standard MRI hardware in TRD patients, enabling in-vivo detection of acute neurochemical changes during stimulation. This method offers a new avenue for probing excitatory/inhibitory balance, neuronal metabolism, and treatment mechanisms.