Benjamin Kop

All Publications

• Parameter optimisation for mitigating somatosensory confounds during transcranial ultrasonic stimulation. Brain stimulation Kop, B. R., de Jong, L., Pauly, K. B., den Ouden, H. E., Verhagen, L. 2025

  Abstract

  BACKGROUND: Transcranial ultrasonic stimulation (TUS) redefines what is possible with non-invasive neuromodulation by offering unparalleled spatial precision and flexible targeting capabilities. However, peripheral confounds pose a significant challenge to reliably implementing this technology. While auditory confounds during TUS have been studied extensively, the somatosensory confound has been overlooked thus far. It will become increasingly vital to quantify and manage this confound as the field shifts towards higher doses, more compact stimulation devices, and more frequent stimulation through the temples where co-stimulation is more pronounced.METHODS: Here, we provide a systematic characterisation of somatosensory co-stimulation during TUS. We also identify the conditions under which this confound can be mitigated most effectively by mapping the confound-parameter space. Specifically, we investigate dose-response effects, pulse shaping characteristics, and transducer-specific parameters.RESULTS: We demonstrate that somatosensory confounds can be mitigated by avoiding near-field intensity peaks in the scalp, spreading energy across a greater area of the scalp, ramping the pulse envelope, and delivering equivalent doses via longer, lower-intensity pulses rather than shorter, higher-intensity pulses. Additionally, higher pulse repetition frequencies and fundamental frequencies reduce somatosensory effects. Through our systematic mapping of the parameter space, we also find preliminary evidence that particle displacement (strain) may be a primary biophysical driving force behind peripheral somatosensory co-stimulation.CONCLUSION: This study provides actionable strategies to minimise somatosensory confounds, which will support the thorough experimental control required to unlock the full potential of TUS for scientific research and clinical interventions.

  View details for DOI 10.1016/j.brs.2025.06.009

  View details for PubMedID 40513772

• Response to 'Safety Considerations for Transcranial Ultrasound Stimulation: A Comment on Nandi et al.'. Brain stimulation Nandi, T., Kop, B. R., Pauly, K. B., Stagg, C. J., Verhagen, L. 2025

  View details for DOI 10.1016/j.brs.2025.03.023

  View details for PubMedID 40209893

• Biophysical effects and neuromodulatory dose of transcranial ultrasonic stimulation. Brain stimulation Nandi, T., Kop, B. R., Naftchi-Ardebili, K., Stagg, C. J., Pauly, K. B., Verhagen, L. 2025

  Abstract

  Transcranial ultrasonic stimulation (TUS) has the potential to usher in a new era for human neuroscience by allowing spatially precise and high-resolution non-invasive targeting of both deep and superficial brain regions. Currently, fundamental research on the mechanisms of interaction between ultrasound and neural tissues is progressing in parallel with application-focused research. However, a major hurdle in the wider use of TUS is the selection of optimal parameters to enable safe and effective neuromodulation in humans. In this paper, we will discuss the major factors that determine the efficacy of TUS. We will discuss the thermal and mechanical biophysical effects of ultrasound, which underlie its biological effects, in the context of their relationships with tunable parameters. Based on this knowledge of biophysical effects, and drawing on concepts from radiotherapy, we propose a framework for conceptualising TUS dose.

  View details for DOI 10.1016/j.brs.2025.02.019

  View details for PubMedID 40054576

• A practical guide to transcranial ultrasonic stimulation from the IFCN-endorsed ITRUSST consortium. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology Murphy, K. R., Nandi, T., Kop, B., Osada, T., Lueckel, M., N'Djin, W. A., Caulfield, K. A., Fomenko, A., Siebner, H. R., Ugawa, Y., Verhagen, L., Bestmann, S., Martin, E., Butts Pauly, K., Fouragnan, E., Bergmann, T. O. 2025; 171: 192-226

  Abstract

  Low-intensity Transcranial Ultrasonic Stimulation (TUS) is a non-invasive brain stimulation technique enabling cortical and deep brain targeting with unprecedented spatial accuracy. Given the high rate of adoption by new users with varying levels of expertise and interdisciplinary backgrounds, practical guidelines are needed to ensure state-of-the-art TUS application and reproducible outcomes. Therefore, the International Transcranial Ultrasonic Stimulation Safety and Standards (ITRUSST) consortium has formed a subcommittee, endorsed by the International Federation of Clinical Neurophysiology (IFCN), to develop recommendations for best practices in human TUS applications. The practical guide presented here provides a brief introduction into ultrasound physics and sonication parameters. It explains the requirements of TUS lab equipment and transducer selection and discusses experimental design and procedures alongside potential confounds and control conditions. Finally, the guide elaborates on essential steps of application planning for stimulation safety and efficacy, as well as considerations when combining TUS with neuroimaging, electrophysiology, or other brain stimulation techniques. We hope that this practical guide to TUS will assist both novice and experienced users in planning and conducting high-quality studies and provide a solid foundation for further advancements in this promising field.

  View details for DOI 10.1016/j.clinph.2025.01.004

  View details for PubMedID 39933226

• The relationship between parameters and effects in transcranial ultrasonic stimulation. Brain stimulation Nandi, T., Kop, B. R., Pauly, K. B., Stagg, C. J., Verhagen, L. 2024

  Abstract

  Transcranial ultrasonic stimulation (TUS) is rapidly gaining traction for non-invasive human neuromodulation, with a pressing need to establish protocols that maximise neuromodulatory efficacy. In this review, we aggregate and examine empirical evidence for the relationship between tunable TUS parameters and in vitro and in vivo outcomes. Based on this multiscale approach, TUS researchers can make better informed decisions about optimal parameter settings. Importantly, we also discuss the challenges involved in extrapolating results from prior empirical work to future interventions, including the translation of protocols between models and the complex interaction between TUS protocols and the brain. A synthesis of the empirical evidence suggests that larger effects will be observed at lower frequencies within the sub-MHz range, higher intensities and pressures than commonly administered thus far, and longer pulses and pulse train durations. Nevertheless, we emphasise the need for cautious interpretation of empirical data from different experimental paradigms when basing protocols on prior work as we advance towards refined TUS parameters for human neuromodulation.

  View details for DOI 10.1016/j.brs.2024.10.008

  View details for PubMedID 39447740

• Auditory confounds can drive online effects of transcranial ultrasonic stimulation in humans. eLife Kop, B. R., Shamli Oghli, Y., Grippe, T. C., Nandi, T., Lefkes, J., Meijer, S. W., Farboud, S., Engels, M., Hamani, M., Null, M., Radetz, A., Hassan, U., Darmani, G., Chetverikov, A., den Ouden, H. E., Bergmann, T. O., Chen, R., Verhagen, L. 2024; 12

  Abstract

  Transcranial ultrasonic stimulation (TUS) is rapidly emerging as a promising non-invasive neuromodulation technique. TUS is already well-established in animal models, providing foundations to now optimize neuromodulatory efficacy for human applications. Across multiple studies, one promising protocol, pulsed at 1000 Hz, has consistently resulted in motor cortical inhibition in humans (Fomenko et al., 2020). At the same time, a parallel research line has highlighted the potentially confounding influence of peripheral auditory stimulation arising from TUS pulsing at audible frequencies. In this study, we disentangle direct neuromodulatory and indirect auditory contributions to motor inhibitory effects of TUS. To this end, we include tightly matched control conditions across four experiments, one preregistered, conducted independently at three institutions. We employed a combined transcranial ultrasonic and magnetic stimulation paradigm, where TMS-elicited motor-evoked potentials (MEPs) served as an index of corticospinal excitability. First, we replicated motor inhibitory effects of TUS but showed through both tight controls and manipulation of stimulation intensity, duration, and auditory masking conditions that this inhibition was driven by peripheral auditory stimulation, not direct neuromodulation. Furthermore, we consider neuromodulation beyond driving overall excitation/inhibition and show preliminary evidence of how TUS might interact with ongoing neural dynamics instead. Primarily, this study highlights the substantial shortcomings in accounting for the auditory confound in prior TUS-TMS work where only a flip-over sham and no active control was used. The field must critically reevaluate previous findings given the demonstrated impact of peripheral confounds. Furthermore, rigorous experimental design via (in)active control conditions is required to make substantiated claims in future TUS studies. Only when direct effects are disentangled from those driven by peripheral confounds can TUS fully realize its potential for research and clinical applications.

  View details for DOI 10.7554/eLife.88762

  View details for PubMedID 39190585

  View details for PubMedCentralID PMC11349300

• Selective modulation of interhemispheric connectivity by transcranial alternating current stimulation influences binaural integration. Proceedings of the National Academy of Sciences of the United States of America Preisig, B. C., Riecke, L., Sjerps, M. J., Kösem, A., Kop, B. R., Bramson, B., Hagoort, P., Hervais-Adelman, A. 2021; 118 (7)

  Abstract

  Brain connectivity plays a major role in the encoding, transfer, and integration of sensory information. Interregional synchronization of neural oscillations in the γ-frequency band has been suggested as a key mechanism underlying perceptual integration. In a recent study, we found evidence for this hypothesis showing that the modulation of interhemispheric oscillatory synchrony by means of bihemispheric high-density transcranial alternating current stimulation (HD-TACS) affects binaural integration of dichotic acoustic features. Here, we aimed to establish a direct link between oscillatory synchrony, effective brain connectivity, and binaural integration. We experimentally manipulated oscillatory synchrony (using bihemispheric γ-TACS with different interhemispheric phase lags) and assessed the effect on effective brain connectivity and binaural integration (as measured with functional MRI and a dichotic listening task, respectively). We found that TACS reduced intrahemispheric connectivity within the auditory cortices and antiphase (interhemispheric phase lag 180°) TACS modulated connectivity between the two auditory cortices. Importantly, the changes in intra- and interhemispheric connectivity induced by TACS were correlated with changes in perceptual integration. Our results indicate that γ-band synchronization between the two auditory cortices plays a functional role in binaural integration, supporting the proposed role of interregional oscillatory synchrony in perceptual integration.

  View details for DOI 10.1073/pnas.2015488118

  View details for PubMedID 33568530

  View details for PubMedCentralID PMC7896308

• Stimulating the deprived motor 'hand' area causes facial muscle responses in one-handers. Brain stimulation Amoruso, E., Kromm, M., Spampinato, D., Kop, B., Muret, D., Rothwell, J., Rocchi, L., Makin, T. R. 2021; 14 (2): 347-350

  View details for DOI 10.1016/j.brs.2021.01.022

  View details for PubMedID 33549718