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Turi, Z.

Publications and source records attributed to Turi, Z..

10 recordsLinked to original sources

Human cortical slices reveal pulse-number-dependent synaptic plasticity during theta-burst magnetic stimulation

Theta-burst transcranial magnetic stimulation is widely used to modulate human brain activity in clinical and experimental settings, yet how clinically relevant stimulation protocols engage synaptic plasticity in human cortical circuits remains poorly understood. Here, we combined controlled magnetic stimulation of viable adult human cortical slices with single-cell electrophysiology to determine whether pulse number constrains synaptic plasticity during intermittent theta-burst stimulation (iTBS). As a functional reference, 10 Hz repetitive magnetic stimulation delivered with 900 pulses robustly potentiated excitatory synaptic transmission in human cortical pyramidal neurons. Similarly, iTBS900 significantly potentiated AMPA receptor-mediated miniature excitatory postsynaptic currents. In contrast, the clinically established 600-pulse iTBS protocol failed to reliably induce detectable synaptic plasticity under otherwise identical stimulation conditions. Paired within-patient experiments confirmed distinct synaptic responses to iTBS600 and iTBS900 in the same human cortical tissue preparations. Together, these findings identify pulse number as an important determinant of theta-burst magnetic stimulation-induced synaptic plasticity in human cortical microcircuits and highlight stimulation dose as a relevant parameter for the design and refinement of therapeutic stimulation protocols.

neuroscience↗

Virtual reality headset geometry constrains dorsolateral prefrontal cortex targeting with transcranial magnetic stimulation

BackgroundThe integration of virtual reality (VR) and non-invasive brain stimulation (NIBS), particularly transcranial magnetic stimulation (TMS), represents a promising approach for closed-loop neuromodulation. Yet the concurrent application remains limited, partly due to insufficient characterization of hardware compatibility of head-mounted displays with standard TMS coil placement protocols. ObjectiveTo systematically quantify the coil-to-scalp distance constraints imposed by VR headsets across cortical targets and coil orientations and to determine feasible intensity compensation ranges based on stimulator output parameters. MethodsNeuronavigated coil positioning was performed on five anatomically realistic 3D-printed head models across 26 scalp positions in eight coil orientations based on the 10-10 EEG system and dorsolateral prefrontal cortex (DLPFC) using two VR headsets of notably different form factors (Meta Quest 2 and Bigscreen Beyond). The deviations of coil positions from intended targets were registered and quantified as coil-to-scalp distance displacement. Individual electric field (E-field) simulations were conducted in SimNIBS at the F3 position across 4-40 mm coil-to-scalp distance to characterize field decay and assess the limits of intensity compensation. ResultsBoth in the directed DLPFC targeting and in systematic scalp positions evaluation, the Meta Quest 2 headset substantially increased coil-to-scalp distance over prefrontal regions, exceeding the compensable range across all metrics. The Bigscreen Beyond headset produced significantly smaller coil-to-scalp distance displacement in prefrontal regions, remaining within feasible E-field intensity compensation limits. Single-pulse and iTBS protocols did not induce functional interference with the hardware under realistic targeting conditions. ConclusionVR headset geometry is the primary determinant of concurrent VR-TMS feasibility. The findings define practical quantitative hardware design requirements and boundaries for future integrated VR-TMS systems and provide a practical framework for optimizing existing VR-TMS protocols.

neuroscience↗

Efficient Gaussian Process-based Motor Hotspot Hunting with Concurrent Optimization of TMS Coil Location and Orientation

BACKGROUNDTranscranial magnetic stimulation (TMS) is a widely used non-invasive brain stimulation technique in neuroscience research and clinical applications. TMS-based motor hotspot hunting, the process of identifying the optimal scalp location to elicit robust and reliable motor responses, is critical to ensure reproducibility and efficiency, as well as to determine safe and precise stimulation intensities in both healthy participants and patients. Typically, this process targets motor responses in contralateral short hand muscles. However, hotspot hunting remains challenging due to the vast parameter space and time constraints. OBJECTIVETo address this, we present an approach that concurrently optimizes both spatial and angular TMS parameters for hotspot hunting using Gaussian processes and Bayesian optimization. METHODSWe systematically evaluated five state-of-the-art acquisition functions on electromyographic TMS data from eight healthy individuals enhanced by simulated data from generative models. RESULTSOur results consistently demonstrate that optimizing spatial and angular TMS parameters simultaneously enhances the efficacy and spatial precision of hotspot hunting. Furthermore, we provide mechanistic insights into the acquisition function behavior and the impact of coil rotation constraints, revealing critical limitations in current hotspot-hunting strategies. Specifically, we show that arbitrary constraints on coil rotation angle are suboptimal, as they reduce flexibility and fail to account for individual variability. We further demonstrate that acquisition functions differ in sampling strategies and performance. Functions overly emphasizing exploitation tend to converge prematurely to local optima, whereas those balancing exploration and exploitation--particularly Thompson sampling--achieve superior performance. CONCLUSIONThese findings highlight the importance of acquisition function selection and the necessity of removing restrictive coil rotation constraints for effective hotspot hunting. Our work advances TMS-based hotspot identification, potentially reducing participant burden and improving safety in both research and clinical applications beyond the motor cortex.

neuroscience↗

Efficient Prospective Electric Field-Informed Localization of Motor Cortical Targets of Transcranial Magnetic Stimulation

Transcranial magnetic stimulation (TMS) is a versatile non-invasive tool for brain mapping and neu-romodulation in both healthy individuals and patients. Effective TMS-based causal brain mapping relies on precise localization of cortical targets. Current state-of-the-art approaches use statistical methods to quantify the relationship between TMS-induced electric fields (E-fields) and motor evoked potential (MEP) amplitudes. However, this method typically relies on the random selection of coil configurations, which limits its efficacy. In this study, we present a novel optimization strategy for TMS-based motor mapping by prospectively selecting coil configurations based on their E-field characteristics using an iterative sampling algorithm called farthest point sampling (FPS). Through a combination of theoretical analysis, simulation and experimental validation including 10 healthy individuals, we systematically evaluated the performance of FPS against the random sampling approach. Our results demonstrate that FPS is twice as efficient as random sampling in reducing the number of trials required for estimating the motor map, while also being more robust across participants and less susceptible to noise. These findings highlight the potential of FPS to significantly enhance the efficiency of motor mapping, paving the way for the development of more effective TMS mapping algorithms.

neuroscience↗

Axon morphology and intrinsic cellular properties determine repetitive transcranial magnetic stimulation threshold for plasticity

Repetitive transcranial magnetic stimulation (rTMS) is a widely used therapeutic tool in neurology and psychiatry, but its cellular and molecular mechanisms are not fully understood. Standardizing stimulus parameters, specifically electric field strength and direction, is crucial in experimental and clinical settings. It enables meaningful comparisons across studies and facilitating the translation of findings into clinical practice. However, the impact of biophysical properties inherent to the stimulated neurons and networks on the outcome of rTMS protocols remains not well understood. Consequently, achieving standardization of biological effects across different brain regions and subjects poses a significant challenge. This study compared the effects of 10 Hz repetitive magnetic stimulation (rMS) in entorhino-hippocampal tissue cultures from mice and rats, providing insights into the impact of the same stimulation protocol on similar neuronal networks under standardized conditions. We observed the previously described plastic changes in excitatory and inhibitory synaptic strength of CA1 pyramidal neurons in both mouse and rat tissue cultures, but a higher stimulation intensity was required for the induction of rMS-induced synaptic plasticity in rat tissue cultures. Through systematic comparison of neuronal structural and functional properties and computational modeling, we found that morphological parameters of CA1 pyramidal neurons alone are insufficient to explain the observed differences between the groups. However, axon morphologies of individual cells played a significant role in determining activation thresholds. Notably, differences in intrinsic cellular properties were sufficient to account for the 10 % higher intensity required for the induction of synaptic plasticity in the rat tissue cultures. These findings demonstrate the critical importance of axon morphology and intrinsic cellular properties in predicting the plasticity effects of rTMS, carrying valuable implications for the development of computer models aimed at predicting and standardizing the biological effects of rTMS.

neuroscience↗

Microglia mediate synaptic plasticity induced by 10 Hz repetitive magnetic stimulation

Microglia--the resident immune cells of the central nervous system--sense the activity of neurons and regulate physiological brain functions. They have been implicated in the pathology of brain diseases associated with alterations in neural excitability and plasticity. However, experimental and therapeutic approaches that modulate microglia function in a brain-region-specific manner have not been established. In this study, we tested for the effects of repetitive transcranial magnetic stimulation (rTMS), a clinically employed non-invasive brain stimulation technique, on microglia-mediated synaptic plasticity. 10 Hz electromagnetic stimulation triggered a release of plasticity-promoting cytokines from the microglia in organotypic brain tissue cultures, while no changes in microglial morphology or microglia dynamics were observed. Indeed, substitution of tumor necrosis factor alpha (TNF) and interleukin 6 (IL6) preserved synaptic plasticity induced by 10 Hz stimulation in the absence of microglia. Consistent with these findings, in vivo depletion of microglia abolished rTMS-induced changes in neurotransmission in the medial prefrontal cortex (mPFC) of anesthetized mice. We conclude that rTMS affects neural excitability and plasticity by modulating the release of cytokines from microglia.

neuroscience↗

Inhibiting corticospinal excitability by entraining ongoing mu-alpha rhythm in motor cortex

AbstractsSensorimotor mu-alpha rhythm reflects the state of cortical excitability. Repetitive transcranial magnetic stimulation (rTMS) can modulate neural synchrony by inducing periodic electric fields (E-fields) in the cortical networks. We hypothesized that the increased synchronization of mu-alpha rhythm would inhibit the corticospinal excitability reflected by decreased motor evoked potentials (MEP). In seventeen healthy participants, we applied rhythmic, arrhythmic, and sham rTMS over the left M1. The stimulation intensity was individually adapted to 35 mV/mm using prospective E-field estimation. This intensity corresponded to ca. 40% of the resting motor threshold. We found that rhythmic rTMS increased the synchronization of mu-alpha rhythm, increased mu-alpha/beta power, and reduced MEPs. On the other hand, arrhythmic rTMS did not change the ongoing mu-alpha synchronization or MEPs, though it increased the alpha/beta power. We concluded that low intensity, rhythmic rTMS can synchronize mu-alpha rhythm and modulate the corticospinal excitability in M1. HighlightsO_LIWe studied the effect of rhythmic rTMS induced E-field at 35 mV/mm in the M1 C_LIO_LIProspective electric field modeling guided the individualized rTMS intensities C_LIO_LIRhyhtmic rTMS entrained mu-alpha rhythm and modulated mu-alpha/beta power C_LIO_LIArrhythmic rTMS did not synchronize ongoing activity though increased mu-alpha/beta power. C_LIO_LIRhythmic but not arrhythmic or sham rTMS inhibited the cortical excitability in M1 C_LI

neuroscience↗

Short-lived alpha power suppression induced by low-intensity arrhythmic rTMS

This study was conducted to provide a better understanding of the role of electric field strength in the production of aftereffects in resting state scalp electroencephalography by repetitive transcranial magnetic stimulation (rTMS) in humans. We conducted two separate experiments in which we applied rTMS over the left parietal-occipital region. Prospective electric field simulation guided the choice of the individual stimulation intensities. In the main experiment, 16 participants received rhythmic and arrhythmic rTMS bursts at between ca. 20 and 50 mv/mm peak absolute electric field intensities. In the control experiment, another group of 16 participants received sham rTMS. To characterize the aftereffects, we estimated the alpha power (8-14 Hz) changes recorded in the inter-burst intervals, i.e., from 0.2 to 10 seconds after rTMS. We found aftereffects lasting up to two seconds after stimulation with ca. 35 mV/mm. Relative to baseline, alpha power was significantly reduced by the arrhythmic protocol, while there was no significant change with the rhythmic protocol. However, we found no significant long-term, i.e., up to 10-second, differences between the rhythmic and arrhythmic stimulation, or between the rhythmic and sham protocols. Weak arrhythmic rTMS induced short-lived alpha suppression during the inter-burst intervals.

neuroscience↗

Selecting stimulation intensity in repetitive transcranial magnetic stimulation studies: A systematic review between 1991 and 2020

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is an increasingly used, non-invasive brain stimulation technique in neuroscience research and clinical practice with a broad spectrum of suggested applications. Among other parameters, the choice of stimulus intensity and intracranial electric field strength substantially impact rTMS outcome. This review provides a systematic overview of the intensity selection approaches and stimulation intensities used in human rTMS studies. We also examined whether studies report sufficient information to reproduce stimulus intensities in basic science research models. Methods. We performed a systematic review by focusing on original studies published between 1991 and 2020. We included conventional (e.g., 1 Hz or 10 Hz) and patterned protocols (e.g., continuous or intermittent theta burst stimulation). We identified 3,784 articles in total, and we manually processed a representative portion (20%) of randomly selected articles. Results. The majority of the analyzed studies (90% of entries) used the motor threshold (MT) approach and stimulation intensities from 80 to 120% of the MT. For continuous and intermittent theta burst stimulation, the most frequent stimulation intensity was 80% of the active MT. Most studies (92% of entries) did not report sufficient information to reproduce the stimulation intensity. Only a minority of studies (1.03% of entries) estimated the rTMS-induced electric field strengths. Conclusion. We formulate easy-to-follow recommendations to help scientists and clinicians report relevant information on stimulation intensity. Future standardized reporting guidelines may facilitate the use of basic science approaches aiming at better understanding the molecular, cellular, and neuronal mechanisms of rTMS.

neuroscience↗

transcranial Direct Current Stimulation Studies Open Database (tDCS-OD)

Transcranial direct current stimulation (tDCS) is increasingly evaluated for a myriad of clinical indications and performance enhancement mainly related to cognitive and motor applications. As a result tDCS has been tested with diverse inclusion criteria and subject populations. tDCS is customized for applications by many factors, including stimulation dose (montage, current, time), associated training and subject inclusion/exclusion criteria. The rapid proliferation of applications, technological advancements and emerging scientific discoveries presents challenges to the organization and consolidation of tDCS data - which can lead to scientific, clinical and public confusions. In this paper, we develop a system to summarize and consolidate methodological aspects of tDCS, concentrating on study design and the physical parameters of the stimulation. We introduce a community-driven, open access database, where these parameters, including stimulation intensities, duration, electrode sizes, montages, and subject information, are noted for relevant tDCS publications. The transcranial Direct Current Stimulation Studies Open Database (tDCS-OD) (http://tdcsdatabase.com) will support constructive dialogue on research and clinical tDCS applications, critical evaluation of past work, and identification of promising protocols, while reducing ambiguity about stimulation methodology. The database design allows ongoing updates and editing, with transparent version control. At the moment, the database includes information about 56,613 tDCS sessions.

neuroscience↗