Focused Ultrasound Personalized Therapy for the Treatment of Depression (UPSIDE)

Introduction

Major depressive disorder (MDD) is the leading cause of disability worldwide, affecting 300 million people with a lifetime prevalence of 15%. Approximately one third of all MDD patients fail to respond to currently established treatments based on medication and psychotherapy, thus falling into the category of Treatment-Resistant Depression (TRD) patients.

Current Treatment Limitations

Electroconvulsive therapy (ECT), repetitive Transcranial Magnetic Stimulation (tRMS), Vagus nerve stimulation, deep brain stimulation (DBS), and transcranial focused ultrasound (tFUS) still show:

• Poor spatial resolution (ECT, tRMS, tFUS)
• Low network coverage (VNS, DBS)

Average remission rates in clinical trials remain lower than 30%.

Need for Biomarkers

Apart from the existing stimulation hurdles, reliable biomarkers for depression are needed as a diagnostic tool. In the case of neurotechnology (NT), these biomarkers can help determine stimulation efficacy and allow for personalized treatment.

Project Overview

The UPSIDE project proposes a minimally invasive, high spatial resolution, and multi-brain region stimulation and recording system to largely exceed the capabilities of existing NT for depression.

Objectives

Our objective is to research and validate in vivo a hybrid neurotechnology consisting of:

1. An epidural focused ultrasound (eFUS) stimulator employing three-dimensional beamforming
2. A high-density epidural EEG recording system

Technological Innovations

Epidural deployment of these devices will be enabled by novel methods for:

• Massive integration and miniaturization of high-performing piezoelectric ultrasound materials
• High-fidelity organic bioelectronic materials with high energy-efficient complementary metal-oxide semiconductor (CMOS) technology in a biocompatible manner

Expected Outcomes

The UPSIDE project will result in a demonstrator which will allow, for the first time, network stimulation and simultaneous biomarker readout in behavioral experiments with animal models featuring depression-like symptoms. This technological breakthrough will pave the way towards a personalized treatment for TRD.