Biology subjects

Opitz, A.

Publications and source records attributed to Opitz, A..

25 records · Page 2Linked to original sources

bioRxiv2020

Multi-scale Modeling Toolbox for Single Neuron and Subcellular Activity under (repetitive) Transcranial Magnetic Stimulation

Transcranial Magnetic Stimulation (TMS) is a non-invasive brain stimulation technique widely used in research and clinical applications. However, its mechanism of action and the neural response to TMS are still poorly understood. Multi-scale modeling can complement experimental research and provide a framework between the physical input parameters and the subcellular neural effects of TMS. At the macroscopic level, sophisticated numerical models exist to estimate the induced electric fields in whole-brain volume conductor models. However, multi-scale computational modeling approaches to predict TMS cellular and subcellular responses, crucial to understanding TMS plasticity inducing protocols, are not available so far. Here, we develop a multi-scale Neuron Modeling for TMS toolbox (NeMo-TMS) that enables researchers to easily generate accurate neuron models from morphological reconstructions, couple them to the external electric fields induced by TMS, and to simulate the cellular and subcellular responses of the neurons. Both single-pulse and rTMS protocols can be simulated and results visualized in 3D. We openly share our toolbox and provide example scripts and datasets for the user to explore. NeMo-TMS toolbox (https://github.com/OpitzLab/NeMo-TMS) allows researchers a previously not available level of detail and precision in realistically modeling the physical and physiological effects of TMS.

neuroscience↗

bioRxiv2019

Experimental Evaluation of Methods for Real-Time EEG Phase-Specific Transcranial Magnetic Stimulation

Brain oscillations reflect system-level neural dynamics and capture the current brain state. These brain rhythms can be measured noninvasively in humans with electroencephalography (EEG). Up and down states of brain oscillations capture local changes in neuronal excitability. This makes them a promising target for non-invasive brain stimulation methods such as Transcranial Magnetic Stimulation (TMS). Real-time EEG-TMS systems record ongoing brain signals, process the data, and deliver TMS stimuli at a specific brain state. Despite their promise to increase the temporal specificity of stimulation, best practices and technical solutions are still under development. Here, we implement and compare state-of-the-art methods (Fourier based, Autoregressive Prediction) for real-time EEG-TMS and evaluate their performance both in silico and experimentally. We further propose a new robust algorithm for delivering real-time EEG phase-specific stimulation based on short prerecorded EEG training data (Educated Temporal Prediction). We found that Educated Temporal Prediction performs at the same level or better than Fourier-based or Autoregressive methods both in silico and in vivo, while being computationally more efficient. Further, we document a dependency of EEG signal-to-noise ratio (SNR) on algorithm accuracy across all algorithms. In conclusion, our results can give important insights for real-time TMS-EEG technical development as well as experimental design.

neuroscience↗

bioRxiv2019

Dose-dependent effects of transcranial alternating current stimulation on spike timing in awake nonhuman primates

Weak extracellular electric fields can influence spike timing in neural networks. Approaches to impose such fields on the brain in a noninvasive manner have high potential for novel treatments of neurological and psychiatric disorders. One of these methods, transcranial alternating current stimulation (TACS), is hypothesized to affect spike timing and cause neural entrainment. However, the conditions under which these effects occur in-vivo are unknown. Here, we show that TACS modulates spike timing in awake nonhuman primates (NHPs) in a dose-dependent fashion. Recording single-unit activity from pre-and post-central gyrus regions in NHPs during TACS, we found that a larger population of neurons became entrained to the stimulation waveform for higher stimulation intensities. Performing a cluster analysis of changes in interspike intervals, we identified two main types of neural responses to TACS - increased burstiness and phase entrainment. Our results demonstrate the ability of TACS to affect spike-timing in the awake primate brain and identify fundamental neural mechanisms. Concurrent electric field recordings demonstrate that spike-timing changes occur with stimulation intensities readily achievable in humans. These results suggest that novel TACS protocols tailored to ongoing brain activity may be a potent tool to normalize spike-timing in maladaptive brain networks and neurological disease.

neuroscience↗

bioRxiv2018

Comparative Modeling of Transcranial Magnetic and Electric Stimulation in Mouse, Monkey, and Human

Transcranial magnetic stimulation (TMS) and transcranial electric stimulation (TES) are increasingly popular methods to noninvasively affect brain activity. However, their mechanism of action and dose-response characteristics remain under active investigation. Translational studies in animals play a pivotal role in these efforts due to a larger neuroscientific toolset enabled by invasive recordings. In order to translate knowledge gained in animal studies to humans, it is crucial to generate comparable stimulation conditions with respect to the induced electric field in the brain. Here, we conduct a finite element method (FEM) modeling study of TMS and TES electric fields in a mouse, capuchin monkey, and human model. We systematically evaluate the induced electric fields and analyze their relationship to head and brain anatomy. We find that with increasing head size, TMS-induced electric field strength first increases and then decreases according to a two-term exponential function. TES-induced electric field strength strongly decreases from smaller to larger specimen with up to 100x fold differences across species. Our results can serve as a basis to compare and match stimulation parameters across studies in animals and humans.\n\nHIGHLIGHTSO_LITranslational research in brain stimulation should account for large differences in induced electric fields in different organisms\nC_LIO_LIWe simulate TMS and TES electric fields using anatomically realistic finite element models in three species: mouse, monkey, and human\nC_LIO_LITMS with a 70 mm figure-8 coil creates an approximately 2-times weaker electric field in a mouse brain than in monkey and human brains, where electric field strength is comparable\nC_LIO_LITwo-electrode TES creates an approximately 100-times stronger electric field in a mouse brain and 3.5-times stronger electric field in a monkey brain than in a human brain\nC_LI

neuroscience↗

bioRxiv2018

Electric field dynamics in the brain during multi-electrode transcranial electric stimulation

Neural oscillations play a crucial role in communication between remote brain areas. Transcranial electric stimulation with alternating currents (TACS) can manipulate these brain oscillations in a non-invasive manner. Of particular interest, TACS protocols using multiple electrodes with phase shifted stimulation currents were developed to alter the connectivity between two or more brain regions. Typically, an increase in coordination between two sites is assumed when they experience an in-phase stimulation and a disorganization through an anti-phase stimulation. However, the underlying biophysics of multi-electrode TACS has not been studied in detail, thus limiting our ability to develop a mechanistic understanding. Here, we leverage direct invasive recordings from two non-human primates during multi-electrode TACS to show that the electric field magnitude and phase depend on the phase of the stimulation currents in a non-linear manner. Further, we report a novel phenomenon of a \"traveling wave\" stimulation where the location of the electric field maximum changes over the stimulation cycle. Our results provide a basis for a mechanistic understanding of multi-electrode TACS, necessitating the reevaluation of previously published studies, and enable future developments of novel stimulation protocols.

neuroscience↗

bioRxiv2017

Brain state and polarity dependent modulation of brain networks by transcranial direct current stimulation

Transcranial direct current stimulation (TDCS) has been widely used to improve cognitive function. However, current deficiencies in mechanistic understanding hinders wider applicability. To clarify its physiological effects, we acquired fMRI whilst simultaneously acquiring TDCS to the right inferior frontal gyrus (rIFG) of healthy human participants, a region involved in coordinating activity within brain networks. TDCS caused widespread modulation of network activity depending on brain state ( rest or choice reaction time task) and polarity (anodal or cathodal). During task, TDCS increased salience network activation and default mode network deactivation, but had the opposite effect during rest. Furthermore, there was an interaction between brain state and TDCS polarity, with cathodal effects more pronounced during task performance and anodal effects more pronounced during rest. Overall, we show that rIFG TDCS produces brain state and polarity dependent effects within large-scale cognitive networks, in a manner that goes beyond predictions from the current literature.

neuroscience↗

bioRxiv2017

Delineating the macroscale areal organization of the macaque cortex in vivo

Complementing longstanding traditions centered around histology, fMRI approaches are rapidly maturing in delineating brain areal organization at the macroscale. The non-human primate (NHP) provides the opportunity to overcome critical barriers in translational research. Here, we establish the data and scanning conditions for achieving reproducible, stable and internally valid areal parcellations in individuals. We demonstrate that these functional boundaries serve as a functional fingerprint of the individual animals, and can be achieved under anesthesia or awake conditions (rest, naturalistic viewing), though differences between awake and anesthetized states precluded the detection of individual differences across states. Comparison of awake and anesthetized states suggested a more nuanced picture of changes in connectivity for higher order association areas, as well as visual and motor cortex. These results establish feasibility and data requirements for the generation of reproducible individual-specific parcellations in NHP, as well as provide insights into the impact of scan state and motivate efforts toward harmonizing protocols.

neuroscience↗