Solving the Orientation Specific Constraints in Transcranial Magnetic Stimulation by Rotating Fields

Transcranial Magnetic Stimulation (TMS) is a promising technology for both neurology and psychiatry. Positive treatment outcome has been reported, for instance in double blind, multi-center studies on depression. Nonetheless, the application of TMS towards studying and treating brain disorders is still limited by inter-subject variability and lack of model systems accessible to TMS. The latter are required to obtain a deeper understanding of the biophysical foundations of TMS so that the stimulus protocol can be optimized for maximal brain response, while inter-subject variability hinders precise and reliable delivery of stimuli across subjects. Recent studies showed that both of these limitations are in part due to the angular sensitivity of TMS. Thus, a technique that would eradicate the need for precise angular orientation of the coil would improve both the inter-subject reliability of TMS and its effectiveness in model systems. We show here how rotation of the stimulating field relieves the angular sensitivity of TMS and provides improvements in both issues. Field rotation is attained by superposing the fields of two coils positioned orthogonal to each other and operated with a relative phase shift in time. Rotating field TMS (rfTMS) efficiently stimulates both cultured hippocampal networks and rat motor cortex, two neuronal systems that are notoriously difficult to excite magnetically. This opens the possibility of pharmacological and invasive TMS experiments in these model systems. Application of rfTMS to human subjects overcomes the orientation dependence of standard TMS. Thus, rfTMS yields optimal targeting of brain regions where correct orientation cannot be determined (e.g., via motor feedback) and will enable stimulation in brain regions where a preferred axonal orientation does not exist

Deep Learning for real-time neural decoding of grasp

Neural decoding involves correlating signals acquired from the brain to variables in the physical world like limb movement or robot control in Brain Machine Interfaces. In this context, this work starts from a specific pre-existing dataset of neural recordings from monkey motor cortex and presents a Deep Learning-based approach to the decoding of neural signals for grasp type classification. Specifically, we propose here an approach that exploits LSTM networks to classify time series containing neural data (i.e., spike trains) into classes representing the object being grasped. The main goal of the presented approach is to improve over state-of-the-art decoding accuracy without relying on any prior neuroscience knowledge, and leveraging only the capability of deep learning models to extract correlations from data. The paper presents the results achieved for the considered dataset and compares them with previous works on the same dataset, showing a significant improvement in classification accuracy, even if considering simulated real-time decoding

Transition management for the smooth flight of a small autonomous helicopter

This work is centered in the definition of a transition management system for a small autonomous helicopter based on trajectory smoothing and a finite state machine (FSM). A smooth flight schedule decreases transients originated by direction changes and flight mode transitions (e.g., horizontal flight to hover mode). Although previous works have presented trajectory generation and FSM oriented controls, no previous studies have mixed these approaches in a single framework together with speed transitions. The proposed methods are validated in simulation with a realistic dynamic model of a small helicopter. © 2009 Springer Science+Business Media B.V

Chronaxie Measurements in Patterned Neuronal Cultures from Rat Hippocampus

Excitation of neurons by an externally induced electric field is a long standing question that has recently attracted attention due to its relevance in novel clinical intervention systems for the brain. Here we use patterned quasi one-dimensional neuronal cultures from rat hippocampus, exploiting the alignment of axons along the linear patterned culture to separate the contribution of dendrites to the excitation of the neuron from that of axons. Network disconnection by channel blockers, along with rotation of the electric field direction, allows the derivation of strength-duration (SD) curves that characterize the statistical ensemble of a population of cells. SD curves with the electric field aligned either parallel or perpendicular to the axons yield the chronaxie and rheobase of axons and dendrites respectively, and these differ considerably. Dendritic chronaxie is measured to be about 1 ms, while that of axons is on the order of 0.1 ms. Axons are thus more excitable at short time scales, but at longer time scales dendrites are more easily excited. We complement these studies with experiments on fully connected cultures. An explanation for the chronaxie of dendrites is found in the numerical simulations of passive, realistically structured dendritic trees under external stimulation. The much shorter chronaxie of axons is not captured in the passive model and may be related to active processes. The lower rheobase of dendrites at longer durations can improve brain stimulation protocols, since in the brain dendrites are less specifically oriented than axonal bundles, and the requirement for precise directional stimulation may be circumvented by using longer duration fields

Apparatus used to stimulate neuronal cultures with external electric fields.

<p>(A) Waveforms of the measured applied voltage between the electrodes (upper row) and within the fluid (lower row), approximately at the center of the experimental cell where the culture is located. Left column is for pulse durations of 1ms and the right is for durations of 100 μs. (B) The plastic insert with one pair of electrodes used to stimulate the neuronal culture. The electrode wires are indicated in the picture by arrows. A plastic rim extending into the medium locates the two parallel platinum wire electrodes about 1 mm above the culture. (C) The device used to stimulate the neuronal culture with two orthogonal pairs of electrodes. A plastic rim holds two pairs of platinum electrodes about 1mm above the culture, which are denoted in the picture by arrows. (D) Sketch of the electrical circuit for a pair of electrodes that is driven by a single square pulse with varying durations. The electric field created between these electrodes is used to stimulate a neuronal network cultured on a glass coverslip. (E, F) Sketch of the electrical circuit for two pairs of electrodes that are fed with separate single square pulses with varying durations (synchronized but with no common ground). Changing the relative amplitudes changes the orientation of the electrical field, which is used to directionally stimulate a neuronal network cultured on a cover slip. (G) Sketch of the electrical circuit for obtaining a rotating electric field. Two pairs of electrodes are each fed with one cycle of sine or of cosine voltage pulses (i.e. two signals with the same amplitude but phase shifted by π/2).</p

Measuring population threshold from fluorescence intensity as a function of the field strength for a given duration.

<p>(A) Fluorescence intensity measured using calcium imaging, from about 100 neurons in the 1D culture that are within the field of view of the microscope. CNQX, APV and bicuculline were used to completely disconnect the network. External stimulation was given at times marked by the vertical grey lines. The four blue curves show typical fluorescence responses of the network, with excitation seen as a sharp increase in fluorescence intensity. The number adjacent to the grey line represents the amplitude of the stimulating signal (in volts). (B) At a fixed pulse duration, the intensity of the normalized fluorescence vs. voltage used for stimulation is a cumulative Gaussian distribution. The mean minimal amplitude needed for stimulation (“Strength”) was obtained by fitting each experimentally measured fluorescence intensity as a function of the electric field amplitude to a cumulative Gaussian distribution (the Error function) and extracting the expectation value of the Gaussian, The half maximum of this curve is thus taken as the threshold for excitation of the neuronal population.</p

Comparison of excitation with a rotating vs. uni-directional field with and without the A-type channel blocker 4-AP.

<p>(A) Pulse durations needed for excitation with rotating (light green) vs. uni-direction (dark green) for [Ca2+] = 1 mM and [Mg2+] = 1 mM, similarly for [Ca2+] = 4 mM and [Mg2+] = 2 mM (center, light and dark blue) and for [Ca2+] = 4 mM and [Mg2+] = 2 mM with addition of 2 mM 4-AP (right, light and dark red). The effect of the change in concentration of ions is to decrease the membrane voltage, countering the increased excitability caused by blocking the A-type channels, which causes the durations needed to be overall about four times longer with higher ionic concentrations. (B) The ratios between durations needed for excitation with a rotating pulse and a uni-directional pulse for the three conditions measured: low concentrations of [Ca2+] and [Mg2+] (green), high concentration of [Ca2+] and [Mg2+] (blue), and high ionic concentrations with the addition of 4-AP (red). Addition of calcium and magnesium does not affect the ratio. Addition of 4-AP does shorten the duration of the uni-directional field but not of the rotating pulse.</p

Angular dependence of minimal durations and amplitudes needed for exciting a connected 1D culture with varying angles with respect to the linear culture.

<p>(A) A typical example of an experiment with constant amplitude (±22 V) and varying pulse durations. The pulse duration is represented by the distance from the center of the circle. In this example a square pulse of 400 μs was needed to excite with the field perpendicular to the lines (90°), while only 150 μs was needed for excitation parallel to the lines (0°). (B) Fixed amplitude results averaged over 15 different cultures. To allow averaging, the pulse duration in each experiment is normalized by the duration needed to excite the culture in 90 degrees and is plotted as the distance from the center. The red star represents the average, and the black crosses the standard error. The angles are “folded” to the first quadrant (e.g. 330°→30°). (C) A typical example of an experiment with pulse duration held fixed while the amplitude is varied. The distance from the center of the circle is now the amplitude of the square pulse (in Volts) needed for excitation of the culture. The duration was held constant throughout each experiment and was determined as the minimal duration needed for the excitation at ±22 V for 90° orientation. (D) Average over 5 different cultures. The red star represents the average, and the black crosses the standard error. The amplitude of each experiment is normalized by the amplitude needed for excitation at 90°. Inset: Schematic for the setup with 1D networks. The 1D culture is grown on thin lines (width 170 μm, length 11 mm). An external voltage is applied by two perpendicular pairs of bath electrodes, driven by two separate power supplies. The ratio between the amplitude of each pair of electrodes determines the angle of the electrical field allowing measurement of different angles without the need to manually rotate the culture.</p

Cross coil experiments.

<p>a) A photograph of the cross coil used in the experiment. The two coils interlock on perpendicular planes and connect to two independent stimulators. b) A photograph of the glass sphere that was custom made to fit inside the cross coil. The glass coverslip, on which the neuronal culture grows, and the fluid medium were inserted through a slot located at the top of the sphere. The coverslip lay on a flattened base at the bottom of the sphere and was observed via a viewing aperture, which was sealed with optically transparent glass. See also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0086794#pone.0086794.s003" target="_blank">Video S1</a>. c) Schematic of the setup – the coverslip (red) was placed in a glass sphere inside the cross coil while an inverted epi-fluorescence microscope monitored neuronal activity. Scale bars in a–c are <i>2 cm</i>. d) Cross coil setup for rat experiments. The rat's head was positioned inside the cross coil (in place of the glass sphere, which was not used). EMG electrodes recorded muscle potentials from the Gastrocnemius. The EMG data was digitized and synchronized with the rfTMS pulses to assess the motor response to rfTMS. e) The induced electric field in the cross coil was measured using a pick-up coil oriented first on the plane of one of the coils (solid line) and then on the plane of the second coil (dashed line). The Magstim stimulator was loaded to <i>100%</i> and the HMS was loaded with <i>3.5 kV</i> (see details in the Methods section). f) A reconstruction of the effective electric field created from the sum of the two perpendicular components measured in e) with the field of coil #1 directed along the x-axis and the field of coil #2 along the y-axis. The effective field was reconstructed for a specific location just inside the poles of the cross coil (‘Neuronal culture’ arrow in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0086794#pone-0086794-g002" target="_blank">Figure 2d</a>). The effective field completes <i>¾</i> of a spiral cycle during the magnetic pulses cycle, as indicated by the black arrows.</p