Functional Specificity of TPS Brain Stimulation Effects in Patients with Alzheimer's Disease: A Follow-up fMRI Analysis.
Authors: Dörl G, Matt E, Beisteiner R
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. 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. 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. Results argue for a high functional specificity of ultrasound-based neuromodulation with TPS.
Introduction
Purpose
Transcranial ultrasound stimulation
Study Objective
To determine whether the visuo-constructive decline observed after transcranial pulse stimulation in Alzheimer’s patients is reflected by decreased functional connectivity in a visuo-constructive network measured with fMRI.
Animal model / Human subject
Homo sapiens; strain: N/A; age: mean 69.9 years (inclusion ≥18 years); sex: both (11 female, 7 male); n=18
Disease model
Alzheimer's disease
MRI or image guidance method
MRI-guided
Targeted brain region(s)
Dorsolateral Prefrontal Cortex
Outcomes and Safety
Summary of Outcomes
Navigated transcranial pulse stimulation (TPS) improved memory, language and mood when functionally relevant regions were targeted, but visuo-constructive performance declined and functional connectivity (global efficiency) decreased in a visuo-constructive network—particularly the right angular gyrus—which correlated with visuo-constructive test scores. The study did not test or compare multiple focused ultrasound parameter sets (no parameter-specific successes reported).
Duration of biological effect
3 months
Safety-related matter
No safety issues or adverse events were reported; the only negative finding was a decline in visuo-constructive performance, which the authors attribute to omission of relevant stimulation targets and likely natural disease progression rather than TPS-related harm.
Brain Region
Ultrasound Parameters
Ultrasound instrument
NEUROLITH TPS generator (Storz Medical AG, Tägerwilen, Switzerland); Transducer aperture/diameter: None
FUS Intensity
0.10 W/cm2
FUS Mode
pulsed
Pulse duration
0.003 ms
Duration of a single FUS session
20 minutes
Focal Characteristics
Focal depth: None; Focal length: None; Aperture size: None
Treatment frequency
multiple
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