Stanford Advisors


All Publications


  • A real-time all-optical interface for dynamic perturbation of neural activity during behavior. Cell reports methods Zhang, Z., Dzialecka, P., Russell, L. E., Ratto, R., Buetfering, C., Gauld, O. M., Selviah, D. R., Häusser, M. 2025: 101180

    Abstract

    We developed a strategy for implementing a dream experiment in systems neuroscience, where circuit manipulation is guided by the real-time readout of neural activity in behaving mice. The system integrates a state-of-the-art calcium imaging analysis package that achieves rapid online activity readout from two-photon calcium imaging, a custom hologram generation program that targets two-photon optogenetic stimulation of specific neuronal ensembles, and software modules that automate essential steps in running complex all-optical experiments. Proof-of-principle experiments demonstrate that neurons can be automatically detected and recruited into a photostimulation ensemble, closed-loop photoinhibition can be implemented immediately after fast mapping of the functional properties of cortical neurons, and targeted activation can be guided by readout of ongoing activity patterns in behaviorally relevant neuronal ensembles during decision-making.

    View details for DOI 10.1016/j.crmeth.2025.101180

    View details for PubMedID 40972568

  • Pulse-width modulated temporal interference (PWM-TI) brain stimulation. Brain stimulation Luff, C. E., Dzialecka, P., Acerbo, E., Williamson, A., Grossman, N. 2024; 17 (1): 92-103

    Abstract

    Electrical stimulation involving temporal interference of two different kHz frequency sinusoidal electric fields (temporal interference (TI)) enables non-invasive deep brain stimulation, by creating an electric field that is amplitude modulated at the slow difference frequency (within the neural range), at the target brain region.Here, we investigate temporal interference neural stimulation using square, rather than sinusoidal, electric fields that create an electric field that is pulse-width, but not amplitude, modulated at the difference frequency (pulse-width modulated temporal interference, (PWM-TI)).We show, using ex-vivo single-cell recordings and in-vivo calcium imaging, that PWM-TI effectively stimulates neural activity at the difference frequency at a similar efficiency to traditional TI. We then demonstrate, using computational modelling, that the PWM stimulation waveform induces amplitude-modulated membrane potential depolarization due to the membrane's intrinsic low-pass filtering property.PWM-TI can effectively drive neural activity at the difference frequency. The PWM-TI mechanism involves converting an envelope amplitude-fixed PWM field to an amplitude-modulated membrane potential via the low-pass filtering of the passive neural membrane. Unveiling the biophysics underpinning the neural response to complex electric fields may facilitate the development of new brain stimulation strategies with improved precision and efficiency.

    View details for DOI 10.1016/j.brs.2023.12.010

    View details for PubMedID 38145754

  • Noninvasive theta-burst stimulation of the human striatum enhances striatal activity and motor skill learning. Nature neuroscience Wessel, M. J., Beanato, E., Popa, T., Windel, F., Vassiliadis, P., Menoud, P., Beliaeva, V., Violante, I. R., Abderrahmane, H., Dzialecka, P., Park, C. H., Maceira-Elvira, P., Morishita, T., Cassara, A. M., Steiner, M., Grossman, N., Neufeld, E., Hummel, F. C. 2023; 26 (11): 2005-2016

    Abstract

    The stimulation of deep brain structures has thus far only been possible with invasive methods. Transcranial electrical temporal interference stimulation (tTIS) is a novel, noninvasive technology that might overcome this limitation. The initial proof-of-concept was obtained through modeling, physics experiments and rodent models. Here we show successful noninvasive neuromodulation of the striatum via tTIS in humans using computational modeling, functional magnetic resonance imaging studies and behavioral evaluations. Theta-burst patterned striatal tTIS increased activity in the striatum and associated motor network. Furthermore, striatal tTIS enhanced motor performance, especially in healthy older participants as they have lower natural learning skills than younger subjects. These findings place tTIS as an exciting new method to target deep brain structures in humans noninvasively, thus enhancing our understanding of their functional role. Moreover, our results lay the groundwork for innovative, noninvasive treatment strategies for brain disorders in which deep striatal structures play key pathophysiological roles.

    View details for DOI 10.1038/s41593-023-01457-7

    View details for PubMedID 37857774

    View details for PubMedCentralID PMC10620076

  • Focal non-invasive deep-brain stimulation with temporal interference for the suppression of epileptic biomarkers. Frontiers in neuroscience Acerbo, E., Jegou, A., Luff, C., Dzialecka, P., Botzanowski, B., Missey, F., Ngom, I., Lagarde, S., Bartolomei, F., Cassara, A., Neufeld, E., Jirsa, V., Carron, R., Grossman, N., Williamson, A. 2022; 16: 945221

    Abstract

    Neurostimulation applied from deep brain stimulation (DBS) electrodes is an effective therapeutic intervention in patients suffering from intractable drug-resistant epilepsy when resective surgery is contraindicated or failed. Inhibitory DBS to suppress seizures and associated epileptogenic biomarkers could be performed with high-frequency stimulation (HFS), typically between 100 and 165 Hz, to various deep-seated targets, such as the Mesio-temporal lobe (MTL), which leads to changes in brain rhythms, specifically in the hippocampus. The most prominent alterations concern high-frequency oscillations (HFOs), namely an increase in ripples, a reduction in pathological Fast Ripples (FRs), and a decrease in pathological interictal epileptiform discharges (IEDs).In the current study, we use Temporal Interference (TI) stimulation to provide a non-invasive DBS (130 Hz) of the MTL, specifically the hippocampus, in both mouse models of epilepsy, and scale the method using human cadavers to demonstrate the potential efficacy in human patients. Simulations for both mice and human heads were performed to calculate the best coordinates to reach the hippocampus.This non-invasive DBS increases physiological ripples, and decreases the number of FRs and IEDs in a mouse model of epilepsy. Similarly, we show the inability of 130 Hz transcranial current stimulation (TCS) to achieve similar results. We therefore further demonstrate the translatability to human subjects via measurements of the TI stimulation vs. TCS in human cadavers. Results show a better penetration of TI fields into the human hippocampus as compared with TCS.These results constitute the first proof of the feasibility and efficiency of TI to stimulate at depth an area without impacting the surrounding tissue. The data tend to show the sufficiently focal character of the induced effects and suggest promising therapeutic applications in epilepsy.

    View details for DOI 10.3389/fnins.2022.945221

    View details for PubMedID 36061593

    View details for PubMedCentralID PMC9431367

  • Unsupervised coadaptation of an assistive interface to facilitate sensorimotor learning of redundant control De Santis, D., Dzialecka, P., Mussa-Ivaldi, F. A., IEEE IEEE. 2018: 801-806