Behnam Molaee-Ardekani

Transcranial direct-current stimulation modulates synaptic mechanisms involved in associative learning in behaving rabbits

Transcranial direct-current stimulation (tDCS) is a noninvasive brain stimulation technique that has been successfully applied for modulation of cortical excitability. tDCS is capable of inducing changes in neuronal membrane potentials in a polarity-dependent manner. When tDCS is of sufficient length, synaptically driven after-effects are induced. The mechanisms underlying these after-effects are largely unknown, and there is a compelling need for animal models to test the immediate effects and after-effects induced by tDCS in different cortical areas and evaluate the implications in complex cerebral processes. Here we show in behaving rabbits that tDCS applied over the somatosensory cortex modulates cortical processes consequent to localized stimulation of the whisker pad or of the corresponding area of the ventroposterior medial (VPM) thalamic nucleus. With longer stimulation periods, poststimulation effects were observed in the somatosensory cortex only after cathodal tDCS. Consistent with the polarity-specific effects, the acquisition of classical eyeblink conditioning was potentiated or depressed by the simultaneous application of anodal or cathodal tDCS, respectively, when stimulation of the whisker pad was used as conditioned stimulus, suggesting that tDCS modulates the sensory perception process necessary for associative learning. We also studied the putative mechanisms underlying immediate effects and after-effects of tDCS observed in the somatosensory cortex. Results when pairs of pulses applied to the thalamic VPM nucleus (mediating sensory input) during anodal and cathodal tDCS suggest that tDCS modifies thalamocortical synapses at presynaptic sites. Finally, we show that blocking the activation of adenosine A1 receptors prevents the long-term depression (LTD) evoked in the somatosensory cortex after cathodal tDCS.

Transcranial Current Brain Stimulation (tCS): Models and Technologies

In this paper, we provide a broad overview of models and technologies pertaining to transcranial current brain stimulation (tCS), a family of related noninvasive techniques including direct current (tDCS), alternating current (tACS), and random noise current stimulation (tRNS). These techniques are based on the delivery of weak currents through the scalp (with electrode current intensity to area ratios of about 0.3-5 A/m2) at low frequencies (typically <; 1 kHz) resulting in weak electric fields in the brain (with amplitudes of about 0.2-2 V/m). Here we review the biophysics and simulation of noninvasive, current-controlled generation of electric fields in the human brain and the models for the interaction of these electric fields with neurons, including a survey of in vitro and in vivo related studies. Finally, we outline directions for future fundamental and technological research.

Effects of transcranial Direct Current Stimulation (tDCS) on cortical activity: A computational modeling study

Although it is well-admitted that transcranial Direct Current Stimulation (tDCS) allows for interacting with brain endogenous rhythms, the exact mechanisms by which externally-applied fields modulate the activity of neurons remain elusive. In this study a novel computational model (a neural mass model including subpopulations of pyramidal cells and inhibitory interneurons mediating synaptic currents with either slow or fast kinetics) of the cerebral cortex was elaborated to investigate the local effects of tDCS on neuronal populations based on an in-vivo experimental study. Model parameters were adjusted to reproduce evoked potentials (EPs) recorded from the somatosensory cortex of the rabbit in response to air-puffs applied on the whiskers. EPs were simulated under control condition (no tDCS) as well as under anodal and cathodal tDCS fields. Results first revealed that a feed-forward inhibition mechanism must be included in the model for accurate simulation of actual EPs (peaks and latencies). Interestingly, results revealed that externally-applied fields are also likely to affect interneurons. Indeed, when interneurons get polarized then the characteristics of simulated EPs become closer to those of real EPs. In particular, under anodal tDCS condition, more realistic EPs could be obtained when pyramidal cells were depolarized and, simultaneously, slow (resp. fast) interneurons became de- (resp. hyper-) polarized. Geometrical characteristics of interneurons might provide some explanations for this effect.

From Oscillatory Transcranial Current Stimulation to Scalp EEG Changes: A Biophysical and Physiological Modeling Study

Both biophysical and neurophysiological aspects need to be considered to assess the impact of electric fields induced by transcranial current stimulation (tCS) on the cerebral cortex and the subsequent effects occurring on scalp EEG. The objective of this work was to elaborate a global model allowing for the simulation of scalp EEG signals under tCS. In our integrated modeling approach, realistic meshes of the head tissues and of the stimulation electrodes were first built to map the generated electric field distribution on the cortical surface. Secondly, source activities at various cortical macro-regions were generated by means of a computational model of neuronal populations. The model parameters were adjusted so that populations generated an oscillating activity around 10 Hz resembling typical EEG alpha activity. In order to account for tCS effects and following current biophysical models, the calculated component of the electric field normal to the cortex was used to locally influence the activity of neuronal populations. Lastly, EEG under both spontaneous and tACS-stimulated (transcranial sinunoidal tCS from 4 to 16 Hz) brain activity was simulated at the level of scalp electrodes by solving the forward problem in the aforementioned realistic head model. Under the 10 Hz-tACS condition, a significant increase in alpha power occurred in simulated scalp EEG signals as compared to the no-stimulation condition. This increase involved most channels bilaterally, was more pronounced on posterior electrodes and was only significant for tACS frequencies from 8 to 12 Hz. The immediate effects of tACS in the model agreed with the post-tACS results previously reported in real subjects. Moreover, additional information was also brought by the model at other electrode positions or stimulation frequency. This suggests that our modeling approach can be used to compare, interpret and predict changes occurring on EEG with respect to parameters used in specific stimulation configurations.

Delta waves differently modulate high frequency components of EEG oscillations in various unconsciousness levels

In this paper we investigate the modulation properties of high frequency EEG activities by delta waves during various depth of anesthesia. We show that slow and fast delta waves (0-2 Hz and 2-4 Hz respectively) and high frequency components of the EEG (8-20 Hz) are correlated with each other and there is a kind of phase locking between them that varies with depth of anesthesia. Our analyses show that maximum amplitudes of high frequency components of the EEG signal are appeared in different phases of slow and fast delta waves when the concentration of Desflurane and Propofol anesthetic agents varies in a patient. There are some slight differences in using slow and fast components of delta waves. For instance, when depth of anesthesia changes, biphasic responses of the EEG have more influences on results of the fast delta wave method. In addition, this method obtains more robust and less noisy results compared with the slow delta wave method. Since phase angle between fast EEG oscillations and delta waves indicates the status of information processing in the brain and it changes in various unconsciousness levels, it may improve the performance of other classic methods of determining depth of anesthesia.

A 15-day course of donepezil modulates spectral EEG dynamics related to target auditory stimuli in young, healthy adult volunteers

OBJECTIVE To identify possible electroencephalographic (EEG) markers of donepezils effect on cortical activity in young, healthy adult volunteers at the group level. METHODS Thirty subjects were administered a daily dose of either 5mg donepezil or placebo for 15days in a double-blind, randomized, cross-over trial. The electroencephalogram during an auditory oddball paradigm was recorded from 58 scalp electrodes. Current source density (CSD) transformations were applied to EEG epochs. The event-related potential (ERP), inter-trial coherence (ITC: the phase consistency of the EEG spectrum) and event-related spectral perturbation (ERSP: the EEG power spectrum relative to the baseline) were calculated for the target (oddball) stimuli. RESULTS The donepezil and placebo conditions differed in terms of the changes in delta/theta/alpha/beta ITC and ERSP in various regions of the scalp (especially the frontal electrodes) but not in terms of latency and amplitude of the P300-ERP component. CONCLUSION Our results suggest that ITC and ERSP analyses can provide EEG markers of donepezils effects in young, healthy, adult volunteers at a group level. SIGNIFICANCE Novel EEG markers could be useful to assess the therapeutic potential of drug candidates in Alzheimers disease in healthy volunteers prior to the initiation of Phase II/III clinical studies in patients.

PTMS27 Simulation of scalp EEG signals under tDCS

was the same as those previously reported. In QPS, 360 trains of 4 monophasic magnetic pulses were applied over the contralateral primary motor cortex (M1). We used QPS5 (interstimulus interval (ISI) = 5 ms) and QPS50 (ISI = 50 ms) for inducing LTP/LTD like effects. The inter-train interval (ITI) was fixed at 5 seconds. Results: QPS5 did not induce significant LTP-like effects in HD patients. QPS50 was not able to induce LTD-like effects. Conclusions: QPS did not induce significant plastic changes in HD patients as the same as the other protocols. In HD, the abnormal plasticity of M1 seen here may be produced directly by cortical pathology or secondary by basal ganglia pathology, or by both of them.

PTMS29 A modeling study of the effects of transcranial direct current stimulation (tDCS) on pyramidal cells and interneurons

Introduction: The use of transcranial Direct Current Stimulation (tDCS) has considerably increased both in clinical and research studies. Although it is well-admitted that this non-invasive technique allows for interacting with brain endogenous rhythms, the exact mechanisms by which externally-applied fields modulate the activity of neurons remain elusive. Objective: Introducing a novel computational model of the cerebral cortex, we investigated the local effects of tDCS on neuronal populations. Methods: A combined experimental/computational modeling approach was used. In the experimental model (in vivo, rabbit), evoked potentials (EPs) were recorded in the somatosensory cortex (SSC) in response to air-puffs applied on the whiskers. Averaged EPs were obtained under anodal and cathodal tDCS stimulation in addition to control condition. One stimulation electrode was positioned in front of the SSC as the other was positioned on the contra-lateral ear. The computational approach included for (i) a neural mass model of the cortex which included pyramidal cells and two types of inhibitory interneurons (fast and slow GABAergic currents), (ii) a sub-cortical input to account for the air-puff effect, and (iii) a coupling between the electric field induced by tDCS and the sub-populations of neurons. Results: In control condition, we first determined which model parameters (EPSP/IPSP amplitudes, connectivity) allowed for accurate simulation of actual EPs (peaks and latencies). Results showed that feedforward inhibition was necessary to match actual EP features. Under tDCS condition, simulations revealed that interneurons were also affected by electric fields. Realistic EPs could be obtained when pyramidal cells got de-polarized by anodal tDCS and, simultaneously, slow (resp. fast) interneurons became de(resp. hyper-)polarized. Conclusion: This study provided insights on whether and how an externally-applied field does also affect local interneurons in addition to pyramidal cells.

Designing a planar vector field to investigate the role of a slow variable in an enhanced mean-field model during general anesthesia

Local mean-field models (MFMs) describe regional brain activities by some connected differential equations. In an overall view, constituting variables of these differential equations can be divided to very fast, fast and slow variables. In this article we propose a method that can be used to determine role of a slow variable in behavior of MFMs. Very fast variables can be adiabatically removed from the equations. Isoclines of fast and slow variables and their corresponding vector field can provide valuable information about model behavior and role of the slow variable in it. The vector field of our interested MFM that is an enhanced MFM designed specially for general anesthesia, is a 3D field (one slow and two fast variables) and it is not so convenient for visually inspecting the role of the slow variable in this model. To afford this problem we design a 2D (planar) vector filed that only considers the slow variable and one of the fast variables