fMRI-guided rTMS in the treatment of auditory verbal hallucinations in schizophrenia: a case report

Abstract

Auditory verbal hallucinations (AVH) are a core symptom of schizophrenia and contribute substantially to patient suffering and disability. They are among the most persistent symptoms and do not respond to medication in a substantial portion of patients. Here, we report the application of task-based functional magnetic resonance imaging (fMRI)-guided repetitive transcranial magnetic stimulation (rTMS) in a patient with treatment-resistant AVH. An individualized stimulation target was identified in the left temporal cortex near Heschl's gyrus using a validated fMRI task. Over a period of 18 months, the patient underwent three cycles of inhibitory 1 Hz rTMS of this target. As a result, AVH severity decreased by 33% and the global symptom score improved by 40%. Functional connectivity analyses revealed an increase in coupling between the temporal target seed and a fronto-cingulate-insular network that has been implicated in reality and performance monitoring. This case highlights the potential of fMRI-guided rTMS as a personalized neuromodulatory therapy for refractory AVH in schizophrenia, warranting further systematic investigation.

Keywords: auditory verbal hallucinations; case report; fMRI; rTMS; schizophrenia.

Figure 1

TMS target location & neural correlates of ‘social localizer’ task across treatment. (A) Coronal, sagittal, and axial slices of the patient’s T1-weighted MRI overlaid with the individualized fMRI peak. The crosshair marks the MNI coordinate of the stimulation target (x = –49, y = 5, z = -1), located in the left temporal cortex near Heschl’s gyrus. (B) Surface-rendered statistical maps of task-related brain activation related to sound loudness during the ‘social localizer’ paradigm before the first (Pre) and between the 4. and 5. (Mid) session of the second rTMS cycle. Overlay of pre (in red) and mid (in blue) treatment, yellow indicating an overlap of activations. (C) Statistical maps of the individual sessions before and after treatment (p< 0.001, uncorrected).

Figure 2

Functional connectivity change across treatment. Functional connectivity of the Heschl’s Gyrus Seed. Brain maps depict regions that exhibited significantly lower FC (p₈₄₇<10^-6Bonferroni) before (Pre), compared with between 4. and 5. rTMS session (Mid; dark blue) or after (Post; mid blue) treatment and their overlap (light blue). Functional connectivity values of the clusters showing differences in at least two pairwise comparisons (Pre-Mid, Pre-Post, Mid-Post) are depicted by boxplots below the brain maps. CER, Cerebellum; INS, Insula; Str, Striatum; CG, Cingulate Gyrus; SFG, Superior Frontal Gyrus; MFG, Middle Frontal Gyrus; PrG, Precentral Gyrus.