First evidence of long-term effects of transcranial pulse stimulation (TPS) on the human brain

Abstract

Background With the high spatial resolution and the potential to reach deep brain structures, ultrasound-based brain stimulation techniques offer new opportunities to non-invasively treat neurological and psychiatric disorders. However, little is known about long-term effects of ultrasound-based brain stimulation. Applying a longitudinal design, we comprehensively investigated neuromodulation induced by ultrasound brain stimulation to provide first sham-controlled evidence of long-term effects on the human brain and behavior. Methods Twelve healthy participants received three sham and three verum sessions with transcranial pulse stimulation (TPS) focused on the cortical somatosensory representation of the right hand. One week before and after the sham and verum TPS applications, comprehensive structural and functional resting state MRI investigations and behavioral tests targeting tactile spatial discrimination and sensorimotor dexterity were performed. Results Compared to sham, global efficiency significantly increased within the cortical sensorimotor network after verum TPS, indicating an upregulation of the stimulated functional brain network. Axial diffusivity in left sensorimotor areas decreased after verum TPS, demonstrating an improved axonal status in the stimulated area. Conclusions TPS increased the functional and structural coupling within the stimulated left primary somatosensory cortex and adjacent sensorimotor areas up to one week after the last stimulation. These findings suggest that TPS induces neuroplastic changes that go beyond the spatial and temporal stimulation settings encouraging further clinical applications.

Retrospective real-world pilot data on transcranial pulse stimulation in mild to severe Alzheimer's patients

“…In conclusion, TPS can be included as an effective and safe add-on treatment for Alzheimer's disease. Even though the first studies (7,9,10), as well as our findings, show promising results, more research is needed, including long-term results in patients. Besides larger sham controlled trials, translational research on the mechanisms of action and effects on cerebral network physiology will be needed.…”

“…However, besides in healthy subjects ( 9 ), no AD placebo-controlled trial has been published for TPS. Furthermore, there is a lack of information about the real-world applicability, safety, and effects of other centers outside the pioneer center in Vienna.…”

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

“…The AG has been implicated in constructional processing [ 20 – 22 ], so a possible hypothesis is that because it is functionally more relevant in the VisNW than, e.g., the precuneus, network function decreased together with corresponding visuo-constructive capacities despite stimulation of the precuneus. Recently, TPS has been shown to induce long-term effects on functional and structural connectivity in connected network areas after stimulation of a somatosensory cortex area [ 23 ]. In a similar vein, Verhagen et al [ 24 ] reported that in macaques not only stimulated brain regions but also their closest connected neighboring areas show modulated activity patterns.…”

Human Ultrasound Neuromodulation: State of the Art

“…Other pioneering patient investigations exist for depression [12], epilepsy [13] and Parkinson's (performed with an unfocused diagnostic system, [14]). The first structural changes induced by human ultrasound neuromodulation have also been published recently using the TPS technology [15,16]. With more than 60 clinical and research centers established, TPS, meanwhile, is the most widely used technology for human ultrasound neuromodulation.Compared to electromagnetic neuromodulation technologies such as Transcranial Magnetic Stimulation (TMS) or Transcranial Direct Current Stimulation (TDCS), ultrasound-based techniques possess two distinct advantages: (1) the targeting of stimulation foci does not depend on the intracerebral conductivity situation-which may grossly be changed due to brain pathology-and (2) ultrasound is not limited to cortical stimulation but is the first non-invasive technique which may precisely target deep areas of the human brain.…”

“…Other pioneering patient investigations exist for depression [ 12 ], epilepsy [ 13 ] and Parkinson’s (performed with an unfocused diagnostic system, [ 14 ]). The first structural changes induced by human ultrasound neuromodulation have also been published recently using the TPS technology [ 15 , 16 ]. With more than 60 clinical and research centers established, TPS, meanwhile, is the most widely used technology for human ultrasound neuromodulation.…”