Biology subjects

Alekseichuk, I.

Publications and source records attributed to Alekseichuk, I..

14 recordsLinked to original sources

bioRxiv2025

Transcranial Alternating Current Stimulation can disrupt or reestablish neural entrainment in a primate model of Parkinson's disease

Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation method which can affect brain oscillations by inducing neuronal entrainment through modulation of spike timings. tACS has high potential for clinical applications in many neurological disorders in which the stimulation can be delivered to modulate oscillatory activity and disrupt pathological brain oscillations. For instance, in Parkinsons Disease (PD), electrophysiological activity in the motor network often exhibits excessive and hyper-synchronized beta oscillations. However, the development of tACS as a therapeutic intervention for pathological oscillations requires the prior establishment of physiologically effective stimulation parameters. We recorded neuronal activity in the motor cortical area of three parkinsonian non-human primates and examined the influence of tACS-induced electric fields on neural firing patterns. We found that weak extracellular electric fields first disrupt beta-band spike timing patterns by changing the preferred spiking phase of neurons but eventually reestablish neural entrainment with altered phase preferences when electric fields are high. Additionally, we show that frequency-matched stimulation, when stimulation frequency corresponds to endogenous oscillatory activity, significantly enhances neural entrainment. Thus, tACS exhibits significant potential for controlling and modulating pathological oscillatory patterns in many neurological disorders such as PD.

neuroscience↗

bioRxiv2024

Layer-specific dynamics of local field potentials in monkey V1 during electrical stimulation

The mammalian neocortex, organized into six cellular layers or laminae, forms a cortical network within layers. Layer specific computations are crucial for sensory processing of visual stimuli within primary visual cortex. Laminar recordings of local field potentials (LFPs) are a powerful tool to study neural activity within cortical layers. Electric brain stimulation is widely used in basic neuroscience and in a large range of clinical applications. However, the layer-specific effects of electric stimulation on LFPs remain unclear. To address this gap, we conducted laminar LFP recordings of the primary visual cortex in monkeys while presenting a flash visual stimulus. Simultaneously, we applied a low frequency sinusoidal current to the occipital lobe with offset frequency to the flash stimulus repetition rate. We analyzed the modulation of visual-evoked potentials with respect to the applied phase of the electric stimulation. Our results reveal that only the deeper layers, but not the superficial layers, show phase-dependent changes in LFP components with respect to the applied current. Employing a cortical column model, we demonstrate that these in vivo observations can be explained by phase-dependent changes in the driving force within neurons of deeper layers. Our findings offer crucial insight into the selective modulation of cortical layers through electric stimulation, thus advancing approaches for more targeted neuromodulation.

biophysics↗

bioRxiv2024

Abnormal mu rhythm state-related cortical and corticospinal responses in chronic stroke

The motor cortexs activity is state-dependent. Specifically, the sensorimotor mu rhythm phase relates to fluctuating levels of primary motor cortex (M1) excitability, previously demonstrated in young and healthy volunteers. However, it is unknown whether this observation is generalizable to individuals with brain lesions after a stroke. We investigated the phase relationship between the mu rhythm and cortical excitability by combining real-time processing of electroencephalography (EEG) signals and transcranial magnetic stimulation (TMS) of M1. In 11 chronic subcortical stroke survivors and 12 similar-aged healthy volunteers, we applied TMS to M1 at the peak, falling, trough, and rising phase of the sensorimotor mu oscillation. As outcome measures, we investigated the M1-to-muscle excitability by measuring motor-evoked potentials (MEPs) and local cortical activation by measuring TMS-evoked potentials (TEPs). We found that M1-to-muscle excitability in stroke survivors and older volunteers shows a phase-dependency similar to that in young healthy adults. That is, MEPs were increased and decreased at the trough and peak of the mu rhythm, respectively. However, individuals with stronger stroke-related motor symptoms showed a decreased phase preference. Further, phase-dependency was abolished in the local cortical activity, as measured with EEG, in the stroke-affected hemisphere, in contrast to the non-affected hemisphere as well as either hemisphere in healthy volunteers. Altogether, these results shed light on the state-dependency of motor cortex excitability after stroke. Our results indicate that the strength of phase preference of TMS motor responses could indicate the severity of motor impairment. These results could enable the development of improved TMS paradigms for recovery of motor impairment after stroke.

neuroscience↗

bioRxiv2024

State dependent motor cortex stimulation reveals distinct mechanisms for corticospinal excitability and cortical responses

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation method which can modulate brain activity by inducing electric fields in the brain. It is a popular tool to study causal brain-behavior relationships. However, brain states vary over time and affect the response of TMS. Neural oscillations can track the current brain state and are a promising marker to guide stimulation timing. Real-time, state-dependent brain stimulation has shown that neural oscillation phase modulates corticospinal excitability reflecting the connection from the primary motor cortex to a target muscle. However, such motor-evoked potentials (MEPs) only indirectly reflect motor cortex activation and are unavailable at other brain regions of interest. The direct and secondary cortical effects of phase-dependent brain stimulation remain an open question. In this study, we recorded the cortical responses during single-pulse transcranial magnetic stimulation (TMS) using electroencephalography (EEG) concurrently with the MEP measurements. TMS was delivered at peak, rising, trough, and falling phases of mu (8-13 Hz) and beta (14-30 Hz) oscillations in the motor cortex. The cortical responses were quantified through TMS-evoked potential components N15, P50, and N100 as peak-to-peak amplitudes (P50-N15 and P50-N100). We further analyzed whether the pre-stimulus frequency band power was predictive of the motor cortical responses. We found a significant main effect of neural oscillation phase on early evoked component (P50-N15). Furthermore, we found an interaction effect of oscillation phase and frequency on both early and late (P50-N100) components. Next, we compared the direct EEG response to the corticospinal excitability reflected by MEP amplitude. Interestingly, the preferred phase of the mu rhythm showed a 900 phase shift between the early TEP components and MEPs. The late component showed the same phase preference between EEG and MEPs. However, such a well-defined relationship did not exist for either of the components during beta phase specific stimulation. In addition, pre-TMS mu oscillatory power and phase significantly predicted both early and late cortical EEG responses when mu rhythm was targeted, indicating the independent causal effects of phase and power. However, only pre-TMS beta power significantly predicted the early and late TEP components when beta rhythm was targeted. Further analysis indicated that both pre-TMS mu and beta power jointly affect early cortical responses. In contrast, the late cortical responses were only influenced by pre-TMS mu power. These findings provide insight to mechanistic understanding of neural oscillation states in cortical and corticospinal activation in humans.

neuroscience↗

bioRxiv2023

Experimental validation of computational models for the prediction of phase distribution during multi-channel transcranial alternating current stimulation

Transcranial alternating current stimulation (tACS) is a widely used noninvasive brain stimulation (NIBS) technique to affect neural activity. Neural oscillations exhibit phase-dependent associations with cognitive functions, and tools to manipulate local oscillatory phases can affect communication across remote brain regions. A recent study demonstrated that multi-channel tACS can generate electric fields with a phase gradient or traveling waves in the brain. Computational simulations using phasor algebra can predict the phase distribution inside the brain and aid in informing parameters in tACS experiments. However, experimental validation of computational models for multi-phase tACS is still lacking. Here, we develop such a framework for phasor simulation and evaluate its accuracy using in vivo recordings in nonhuman primates. We extract the phase and amplitude of electric fields from intracranial recordings in two monkeys during multi-channel tACS and compare them to those calculated by phasor analysis using finite element models. Our findings demonstrate that simulated phases correspond well to measured phases (r = 0.9). Further, we systematically evaluated the impact of accurate electrode placement on modeling and data agreement. Finally, our framework can predict the amplitude distribution in measurements given calibrated tissues conductivity. Our validated general framework for simulating multi-phase, multi-electrode tACS provides a streamlined tool for principled planning of multi-channel tACS experiments.

bioengineering↗

bioRxiv2023

Induced neural phase precession through exogeneous electric fields

The gradual shifting of preferred neural spiking relative to local field potentials (LFPs), known as phase precession, plays a prominent role in neural coding. Correlations between the phase precession and behavior have been observed throughout various brain regions. As such, phase precession is suggested to be a global neural mechanism that promotes local neuroplasticity. However, causal evidence and neuroplastic mechanisms of phase precession are lacking so far. Here we show a causal link between LFP dynamics and phase precession. In three experiments, we modulated LFPs in humans, a non-human primate, and computational models using alternating current stimulation. We show that continuous stimulation of motor cortex oscillations in humans lead to a gradual phase shift of maximal corticospinal excitability by [~]90{degrees}. Further, exogenous alternating current stimulation induced phase precession in a subset of entrained neurons ([~]30%) in the non-human primate. Multiscale modeling of realistic neural circuits suggests that alternating current stimulation-induced phase precession is driven by NMDA-mediated synaptic plasticity. Altogether, the three experiments provide mechanistic and causal evidence for phase precession as a global neocortical process. Alternating current-induced phase precession and consequently synaptic plasticity is crucial for the development of novel therapeutic neuromodulation methods.

neuroscience↗

bioRxiv2022

Mesoscale neural effects of transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation method that is rapidly growing in popularity for studying causal brain-behavior relationships. However, its dose-dependent direct neural mechanisms, i.e., due to electric field or connectivity, and peripheral sensory co-stimulation effects remain debated. Understanding how TMS stimulation parameters affect brain responses is vital for the rational design of TMS protocols. Studying these mechanisms in humans is challenging due to the limited spatiotemporal resolution of available non-invasive neuroimaging methods. Here, we leverage invasive recordings of local field potentials in non-human primates to study TMS mesoscale responses. We demonstrate that early TMS-evoked potentials show a sigmoidal dose-response with stimulation intensity. We further show that stimulation responses are spatially specific. We employ several control conditions to dissociate direct neural responses from auditory and somatosensory co-activation. These results provide crucial evidence regarding TMS neural effects at the brain circuit level. Our findings are highly relevant for interpreting human TMS studies and biomarker developments for TMS target engagement in clinical applications.

neuroscience↗

bioRxiv2022

A minimum effective dose for (transcranial) alternating current stimulation

Transcranial alternating current stimulation (tACS) is a popular method for non-invasive neuromodulation in human research and therapy. However, what constitutes an effective dose in tACS applications is still a matter of investigation and debate. Here, we examined available literature data regarding the effects of alternating current (AC)-induced electric fields on cellular-level neural activity. The literature search identified 16 relevant experimental reports that utilized brain slices, anesthetized rodents, and awake/behaving animal models. We implemented a probabilistic meta-analysis to estimate the minimum effective dose (MED) required for inducing detectable significant neural changes with AC stimulation. The results showed that AC stimulation at 0.3 mV/mm in awake/behaving mammals leads to an 80% probability of inducing minimum neural effects. A similar level of effectiveness in brain slices and anesthetized mammals required 0.7 mV/mm. In conclusion, (transcranial) alternating current stimulation is significantly more effective in awake than in anesthetized brains. The proposed dose targets can serve as a practical guideline for tACS in humans.

neuroscience↗

bioRxiv2022

The phase of sensorimotor mu and beta oscillations has the opposite effect on corticospinal excitability

Neural oscillations in the primary motor cortex (M1) shape corticospinal excitability. Power and phase of ongoing mu (8-13 Hz) and beta (14-30 Hz) activity may mediate motor cortical output. However, the functional dynamics of both mu and beta phase and power relationships and their interaction, are largely unknown. Here, we employ recently developed real-time targeting of the mu and beta rhythm, to apply phase-specific brain stimulation and probe motor corticospinal excitability non-invasively. For this, we used instantaneous read-out and analysis of ongoing oscillations, targeting four different phases (0{degrees}, 90{degrees}, 180{degrees}, and 270{degrees}) of mu and beta rhythms with suprathreshold single-pulse transcranial magnetic stimulation (TMS) to M1. Ensuing motor evoked potentials (MEPs) in the right first dorsal interossei muscle were recorded. Twenty healthy adults took part in this double-blind randomized crossover study. Mixed model regression analyses showed significant phase-dependent modulation of corticospinal output by both mu and beta rhythm. Strikingly, these modulations exhibit a double dissociation. MEPs are larger at the mu trough and rising phase and smaller at the peak and falling phase. For the beta rhythm we found the opposite behavior. Also, mu power, but not beta power, was positively correlated with corticospinal output. Power and phase effects did not interact for either rhythm, suggesting independence between these aspects of oscillations. Our results provide insights into real-time motor cortical oscillation dynamics, which offers the opportunity to improve the effectiveness of TMS by specifically targeting different frequency bands.

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

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↗

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↗