Transcranial direct current stimulation, transcranial magnetic stimulation, transcranial temporal interference and targeted ultrasound therapy are promising methods for neuroscientific research. They allow the targeted stimulation of even deep-seated areas of the brain and may also have prospective applications in medicine. We are therefore very pleased to give Vuk Marković (A06) the opportunity to deepen his knowledge of these methods as part of the treasure chest funding. In the future, the entire SFB 1280 can benefit from the new expert in its ranks. Vuk describes the relevance of the methods as follows:
Over the past few decades, noninvasive brain stimulation methods (e.g. transcranial direct current stimulation (tDCS) (Nitsche & Paulus, 2000) and transcranial magnetic stimulation (TMS) (Barker et al., 1985)) have gained momentum as promising ways to investigate brain functions and its underlying processes. The possibility of causally influencing processes in the brain without tissue damage and observing changes in subjects’ neural activity during experimental tasks opened up a tremendous field of possibilities for addressing numerous research questions. In addition, clinical application of these methods has been established and the designs of new treatment protocols are currently being developed in research institutions worldwide.
On the other hand, the mentioned methods have their limitations and challenges. Most of the challenges are related to focality of the stimulation (i.e. how stimulation affects the desired area but also adjacent and distant areas) and depth of penetration (i.e. how deep could stimulation reach brain tissue). For instance, modeling data suggest that tDCS could have non-homogenous effects on stimulating an area when gyri and sulci geometry is taken into account (Datta et al., 2009). Furthermore, anatomical features such as thicknesses of the cerebrospinal fluid and the skull, the gyral depth and the distance to the anode and cathode of each participant contribute to variations of distribution of the current (Opitz et al., 2015). In addition, tDCS may have effect not only restricted to the area of interest but could also modulate functional connectivity between distant, but functionally associated brain regions (Polania et al., 2011). TMS has similar challenges. For example, focality of the most commonly used figure-of-eight TMS coil was about 5 cm2 (Deng et al., 2013) and there is generally a trade-off between stimulation depth and focality of effects that makes it difficult to activate deeper brain regions without affecting more superficial regions to a greater extent (Chen et al., 2019). Therefore, TMS and tDCS are generally constrained to targeting superficial cortical regions, as their efficacy declines exponentially with depth (Lee et al., 2022).
As the human mind does not stop when there are obstacles, new methods have been developed. For example, focused ultrasound (US) and transcranial temporal interference (TI) stimulation are two approaches that might be used to overcome current limitations.
Apart from application in clinical diagnostics, ultrasound (US) can be used to safely modulate brain activity through the application of acoustic waves with characteristic properties of wavelength, amplitude, and frequency (Sarica et al., 2022; Dell’Italia et al., 2022). Furthermore, it has superior properties regarding focality and depth of the stimulation. For example, focused US can be directed to the brain tissue with a resolution of a few millimeters in diameter, could penetrate the brain to around 15 centimeters and its effect could last from 10-40 minutes after stimulation (Bystritsky et al., 2011). Therefore, this method has the potential to modulate subcortical structures with high precision (e.g. Chain et al., 2021). Also, as the US energy is mechanical rather than electromagnetic, US could be used simultaneously with fMRI for brain mapping relatively uncomplicated (Bystritsky et al., 2011).
Transcranial temporal interference electrical stimulation is another innovative non- invasive brain stimulation method that could neuromodulate deep brain structures while minimizing effects on overlying cortical areas (Grossman et al., 2017). For example, TI stimulation showed a more focal effect compared to transcranial alternating current stimulation (regions of interest were the left hippocampus, left motor area, and thalamus) by substantially reducing co-stimulation in cortical areas in the proximity of stimulation electrodes (von Conta et al., 2021). Furthermore, another study showed that TI stimulation could affect motor learning when the striatum has been targeted (Wessel et al., 2021).
The SFB 1280 has set up a budget for its young scientists to realize their own research ideas. We use the “treasure chest” to finance convincing and independent study concepts of our early career researchers.