Transcranial pulse stimulation (TPS) improves depression in AD patients on state-of-the-art treatment

Eva Matt, Gregor Dörl, Roland Beisteiner, Eva Matt, Gregor Dörl, Roland Beisteiner

Abstract

Introduction: Ultrasound-based brain stimulation is a novel, non-invasive therapeutic approach to precisely target regions of interest. Data from a first clinical trial of patients with Alzheimer's disease (AD) receiving 2-4 weeks transcranial pulse stimulation (TPS) have shown memory and cognitive improvements for up to 3 months, despite ongoing state-of-the-art treatment. Importantly, depressive symptoms also improved.

Methods: We analyzed changes in Beck Depression Inventory (BDI-II) and functional connectivity (FC) changes with functional magnetic resonance imaging in 18 AD patients.

Results: We found significant improvement in BDI-II after TPS therapy. FC analysis showed a normalization of the FC between the salience network (right anterior insula) and the ventromedial network (left frontal orbital cortex).

Discussion: Stimulation of areas related to depression (including extended dorsolateral prefrontal cortex) appears to alleviate depressive symptoms and induces FC changes in AD patients. TPS may be a novel add-on therapy for depression in AD and as a neuropsychiatric diagnosis.

Keywords: Alzheimer's disease; brain stimulation; depression; functional connectivity; functional magnetic resonance imaging; transcranial pulse stimulation; ultrasound.

Conflict of interest statement

This work was supported by research grants from STORZ Medical (including equipment, to R.B). R.B. is President of the Organization for Human Brain Mapping Alpine Chapter and the Austrian Society for fMRI (unpaid). E.M. received travel grants from the Austrian Research Association (ÖFG). G.D. has nothing to declare.

© 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.

Figures

FIGURE 1
FIGURE 1
Depression reduction and functional connectivity correlation. A, Beck Depression Inventory (BDI) score before and after transcranial pulse stimulation (TPS). Depressive symptoms improved significantly (* P < .05) after the stimulation. B, Correlation between BDI‐II depression score and region of interest (ROI)‐to‐ROI functional connectivity (FC) between left frontal orbital cortex (FOrb L) and right anterior insula (AInsula R). Data for the baseline are depicted in blue and for the post‐stimulation sessions after the TPS interventions in red. The significant positive correlation (rho = .434, P = .021, N = 28) indicates that increased FC between these ROIs corresponds to more severe depressive symptoms
FIGURE 2
FIGURE 2
Functional connectivity changes after transcranial pulse stimulation (TPS) treatment in Alzheimer's disease patients. A, Region of interest (ROI) functional connectivity (FC). ROI‐to‐ROI analysis resulted in a significantly lower FC between the left frontal orbital cortex (FOrb L) and the right anterior insula (AInsula R) in the post stimulation session compared to the baseline. B, Individual FC between FOrb L and AInsula R in the baseline and in the post‐stimulation session with the mean values marked in gray. At baseline, the FC values of all patients were positive, but after the stimulation the FC values decreased in 15 out of 18 patients

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