Functional Specificity of TPS Brain Stimulation Effects in Patients with Alzheimer’s Disease: A Follow-up fMRI Analysis

INTRODUCTION: Transcranial pulse stimulation (TPS) has been recently introduced as a novel clinical brain stimulation technique based on highly focused ultrasound pressure pulses. In a first pilot study on clinical effects of navigated and focused ultrasound neuromodulation, a dichotomy of functional effects was found: patients with Alzheimer’s disease improved cognition and language but deteriorated with visuo-constructive functions. METHODS: We analyzed changes in functional connectivity measured with functional magnetic resonance imaging (fMRI) using graph analysis of a visuo-constructive network in 18 patients with Alzheimer’s disease. We calculated the network’s global efficiency and tested for correlation with visuo-constructive test scores to explain this dichotomy. RESULTS: Important visuo-constructive network nodes were not stimulated in the pilot setting and correspondingly global efficiency of a visuo-constructive network was decreased after TPS therapy, compatible with a natural progress of the disease. A correlation between visuo-constructive scores and changes in global efficiency was found. CONCLUSION: Results argue for a high functional specificity of ultrasound-based neuromodulation with TPS.