Mechanisms of magnetic stimulation of central nervous system neurons.

Transcranial magnetic stimulation (TMS) is a stimulation method in which a magnetic coil generates a magnetic field in an area of interest in the brain. This magnetic field induces an electric field that modulates neuronal activity. The spatial distribution of the induced electric field is determined by the geometry and location of the coil relative to the brain. Although TMS has been used for several decades, the biophysical basis underlying the stimulation of neurons in the central nervous system (CNS) is still unknown. To address this problem we developed a numerical scheme enabling us to combine realistic magnetic stimulation (MS) with compartmental modeling of neurons with arbitrary morphology. The induced electric field for each location in space was combined with standard compartmental modeling software to calculate the membrane current generated by the electromagnetic field for each segment of the neuron. In agreement with previous studies, the simulations suggested that peripheral axons were excited by the spatial gradients of the induced electric field. In both peripheral and central neurons, MS amplitude required for action potential generation was inversely proportional to the square of the diameter of the stimulated compartment. Due to the importance of the fiber's diameter, magnetic stimulation of CNS neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. Passive dendrites affect this process primarily as current sinks, not sources. The simulations predict that neurons with low current threshold are more susceptible to magnetic stimulation. Moreover, they suggest that MS does not directly trigger dendritic regenerative mechanisms. These insights into the mechanism of MS may be relevant for the design of multi-intensity TMS protocols, may facilitate the construction of magnetic stimulators, and may aid the interpretation of results of TMS of the CNS

Another piece in the puzzle – A new PPNA site at Bir el-Maksur (Northern Israel)

Salvage excavations held at the site of Bir el-Maksur, Lower Galilee, revealed an extensive Pre-Pottery Neolithic A (PPNA) occupation alongside rich assemblages. Albeit the lack of clear architectural structures, the abundant fi nds demonstrate a wide variety of activities held at this locale, including faunal and floral resource processing and consumption, on-site lithic production and large-scale pyrotechnological activities. A complex secondary burial of two individuals accompanied with what might be interpreted as grave goods (mainly ground stones) indicates more complex, socio-cultural activities as well. As the Neolithic period represents an important departure from Palaeolithic life-ways and the movement toward new economical and social spheres, it is important to bridge the gaps in our current knowledge of the spatial and temporal trends in settlement patterns associated with it. Our aim is thus to attempt a reconstruction of the function of Bir el-Maksur and place it within the larger framework of the PPNA. In this respect, and although hindered by post depositional processes as well as by the restricted extent of the studied area, these excavations illustrate important new data concerning the occupation of the Lower Galilee during this important period.Cet article livre les résultats de la fouille de sauvetage effectuée à Bir el-Maksur, un site du Néolithique pré-céramique A (PPNA) situé en Basse Galilée, dans le nord d’Israël, où a été mise au jour une vaste occupation avec de riches assemblages. Malgré l’absence de structures architecturales claires, les nombreux artefacts permettent de reconstituer une variété d’activités : le traitement de ressources végétales et fauniques et leur consommation, une production lithique in situ et des procédés pyrotechniques à grande échelle. Une sépulture secondaire complexe de deux individus, accompagnés de ce qui pourrait être des objets funéraires (principalement outillage de mouture), indique aussi l’existence d’activités socioculturelles plus complexes. Les fouilles et les assemblages retrouvés sont présentés avec une analyse des activités associées et de leur signification. Le Néolithique représente un mouvement vers de nouvelles sphères économiques et sociales, mais il est important de combler les lacunes dans notre connaissance actuelle des modes de peuplement liés à ce mouvement. Notre objectif est donc de reconstituer la fonction de Bir el-Maksur et replacer ce site dans le cadre chrono-culturel du PPNA. À cet égard et malgré les processus taphonomiques, ainsi que la superficie restreinte de la zone étudiée, ces fouilles apportent des données nouvelles significatives sur l’occupation de la Basse Galilée au cours de cette période importante.Malinsky-Buller Ariel, Aladjem Emil, Givol-Barzilai Yael, Bonnes Doron, Goren Yuval, Yeshurun Reuven, Birkenfeld Michal. Another piece in the puzzle – A new PPNA site at Bir el-Maksur (Northern Israel). In: Paléorient, 2013, vol. 39, n°2. pp. 155-172

Brain activity dissociates mentalization from motivation during an interpersonal competitive game. Brain Imaging Behav. 3:24--37

Abstract Studies demonstrating selective brain networks subserving motivation and mentalization (i.e. attributing states of mind to others) during social interactions have not investigated their mutual independence. We report the results of two fMRI studies using a competitive game requiring players to use implicit 'on-line' mentalization simultaneously with motivational processes of gains and losses in playing against a human or a computer opponent. We delineate a network, consisting of bilateral temporoparietal junction, temporal pole (TP), medial prefrontal cortex (MPFC) and right fusiform gyrus, which is sensitive to the opponent's response (challenging>not challenging the player) and opponent type (human>computer). This network is similar to a known explicit 'off-line' mentalization circuit, suggesting its additional involvement in implicit 'on-line' mentalization, a process more applicable to reallife social interactions. Importantly, only MPFC and TP were selective to mentalization compared to motivation, highlighting their specific operation in attributing states of mind to others during social interactions

Magnetic threshold correlates with current threshold in realistic morphologies.

<p>Neurons were located at the center of the matrix as in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002022#pcbi-1002022-g004" target="_blank">Figure 4</a>. Distance from the plane of the coil was 1 cm, coil radius was 2 cm, 30 loops to the coil. The underdamped pulse was used (R = 0.09 Ω; L = 13 µH; C = 200 µF; τ = 0.4 ms). Excitability was added to all cells using two different models of L5 pyramidal neurons - Larkum et al.'s model (2009) <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002022#pcbi.1002022-Larkum2" target="_blank">[38]</a> (green) and Schaefer et al.'s model (2003) <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002022#pcbi.1002022-Schaefer2" target="_blank">[27]</a> (black). The magnetic threshold correlated with current threshold in pyramidal cell with different current thresholds. Sodium channel activation and inactivation were shifted towards hyperpolarizing potentials to reduce current threshold.</p

The induced electric field generated by the magnetic flux in a Cartesian coordinate system.

<p>The spatial part of the electric field was calculated in Matlab prior to simulation with Equation 18 and then exported from Matlab to NEURON. For the simulation of CNS neurons, matrix size was 4000×4000 µm with a spatial resolution of 1 µm. The center of the matrix field lay 1.98 cm from the center of the coil. The size relation between the matrices and a neuron is demonstrated by a pyramidal neuron located in the center of the field. Distance from the plane of the coil was 1 cm, coil radius was 2 cm, 30 loops to the coil. The permeability constant was 4π*10⁻⁷ H/m. <b>A</b>, The spatial function of the induced electric field. <b>B</b>, The spatial component of the induced electric field along the x-axis. <b>C</b>, The spatial component of the induced electric field along the y-axis.</p

Magnetic stimulation stimulates the somato-axonal compartment in realistic neurons.

<p>The suprathreshold activity of a pyramidal neuron cell exposed to magnetic stimulation. The neuron was located at the center of the matrix as in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002022#pcbi-1002022-g004" target="_blank">Figure 4</a>. Distance from the plane of the coil was 1 cm, coil radius was 2 cm, 30 loops to the coil. The underdamped pulse was used (R = 0.09 Ω; L = 13 µH; C = 200 µF; τ = 0.4 ms). Excitability was added to all cells using a model of neocortical pyramidal neurons <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002022#pcbi.1002022-Schaefer2" target="_blank">[27]</a>. The membrane potential (in mV) along a pyramidal neuron is displayed as pseudo-color in each compartment and several time points following MS initiation are shown in a time-lapse sequence.</p

The location of action potential initiation and the magnetic threshold depend on the location of the soma relative to the coil.

<p><b>A</b>, A soma with a long straight axon containing sections of myelin and nodes of Ranviar was located in a plane below the coil. Soma, axon and node diameters were 20 µm, 1 µm and 0.75 µm, respectively. Soma, axon and nodes lengths were 20 µm, 100 µm and 1 µm, respectively. The view from above shows that the artificial neuron was shifted along the y-axis by one coil radius and along the x-axis by Δx. <b>B</b>, The magnetic threshold decreased with Δx until it reached a minimum at the location corresponding to the maximal gradient of the electric field. The action potential was initiated at the axon for small shifts (Δx<0.05 cm, green dots), and at the soma for larger shifts (black dots). The lowest magnetic threshold was achieved when the soma was located at the largest gradient of the induced electric field.</p