New Publication on TPS and FUS

Therapeutic Perspectives of Transcranial Pulse Stimulation (TPS) and Focused Ultrasound (FUS)

In a recent publication1 by Beisteiner et al, a comprehensive overview of the current state of ultrasound neuromodulation is presented for the first time. The article discusses the available technologies, therapy results and the advantages compared to electromagnetic approaches.

The authors show how the rapid methodological and clinical development in this field opens up completely new therapeutic possibilities for brain diseases. In their opinion, innovative stimulation methods such as transcranial pulse stimulation (TPS) are of great importance, as brain diseases are among the most urgent challenges of our rapidly ageing society and many of these diseases do not yet have effective drugs. In addition, the non-invasive procedures fulfil the wish of many patients for gentle treatment.

State of the Art: Highly Focused Navigated Systems

There are various technical approaches in the field of clinical ultrasound neuromodulation. In the authors’ view, the “state of the art” is clearly the highly focused navigated systems. These make it possible to precisely target individual brain areas on individual magnetic resonance (MR) images. Since every brain is different and pathologies can lead to severe morphological changes in the brain, precise targeting capabilities are essential.

In terms of highly focused systems, the authors differentiate between two neuromodulation approaches – focused ultrasound (FUS) and the much newer, shockwave-based transcranial pulse stimulation (TPS). Compared to FUS, the distinctive feature of TPS pulses is that they are ultra-short pressure pulses (about 3 μs) that produce a stronger mechanical stimulation.

Advantages over electromagnetic stimulation techniques

In their article, the authors highlight the clinical advantages of ultrasound neuromodulation over electromagnetic techniques (TMS, tDCS, tACS) that have been used for decades. They highlight three main advantages: First, the narrow focus of neuromodulation with TPS and FUS offers unprecedented precision in targeting small brain areas. Second, the techniques enable non-invasive, selective and focal deep brain stimulation for the first time. Third, clinical neuromodulation requires stimulation of pathological brains. This involves large changes in the normal conductance situation in the brain. With electromagnetic methods, it is almost impossible to always correctly model this altered conductance for precise individual targeting. In contrast, targeting with TPS/FUS is not affected by conductivity changes.

Clinical effects of neuromodulation with TPS and FUS

The authors list a total of 16 clinical studies on TPS and FUS. Fourteen studies report significant clinical effects, with 13 studies describing benefits for patients. In a study overview, the authors summarise the most important clinical effects. The following clinical effects were described in the listed studies on TPS:

  • Improvement in cognitive scores (CERAD) over 3 months; atrophy reduction; depression reduction. Neuropsychological results are supported by morphological, task-related and functional MRI at rest.
  • Improvement in cognitive scores (ADAS, ADAS-Cog) immediately after treatment.
  • Significant improvements on the Hamilton Depression Rating Scale-17 (HDRS-17).

The authors assess the data on the safety of neuromodulation with TPS and FUS positively: none of the studies described a serious adverse event (SAE). With the clinically most widely used system (TPS), more than 15,000 treatment sessions were performed without serious adverse events (SAE).

Therapeutic perspectives: a broad spectrum of diseases

The authors assess neuromodulation with state-of-the-art TPS and FUS systems as a brain therapy that, although still new, holds great promise. The study data so far open up new therapeutic perspectives, as most of the patients included had already received state of the art therapies before and the clinical improvements should therefore be seen as an additional effect.

Clinical research on the effect of TPS and FUS is currently increasing rapidly – at least 17 further patient studies are already underway or are to be conducted. They cover a broad spectrum of diseases: Temporal lobe epilepsy, depression, treatment-resistant schizophrenia, opioid abuse, post-traumatic stress disorder, anxiety disorders, obsessive-compulsive disorder, brain tumour, essential tremor, acute and chronic pain, headache, mild cognitive impairment, dementia and Parkinson’s disease.

The authors call for clinical trials to increasingly include sham conditions and independent neurophysiological measurements (MRI, electrophysiology). Many of the already registered studies already fulfil these demands. In addition, the authors would like to see larger patient numbers for future studies in order to be able to make even more precise statements about the clinical effects of TPS and FUS.


Beisteiner R, Hallett M, Lozano A.M. Ultrasound Neuromodulation as a New Brain Therapy. Adv Sci. 2023; Mar 24: 2205634. DOI: 10.1002/advs.202205634 (link: