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1d - TMS in cell culture and brain

Andreas Neef and Walter Paulus

The goal of this project is to achieve a rational design of therapeutic treatment paradigms for transcranial magnetic stimulation (TMS) by uncovering its cellular physiological basis using a combination of cell culture and in vivo experiments with computational studies. It builds on a collaboration with Elisha Moses and Assaf Rotem from the Weizmann Institute in Rehovot, Israel, who recently showed that patterned neuronal cultures are sensitive to magnetic stimulation (MS). This allows us now for the first time to conveniently study the cellular basis of TMS induced changes.

Transcranial magnetic stimulation (TMS) induces complex transient electric fields in a small area of the cortex by means of focused magnetic pulses which are delivered with a coil placed over the skull. It is increasingly used to treat neuro-psychiatric disorders (Rossini and Rossi, 2007) and is an intriguing tool in human neuroscience research e.g. to induce localized “virtual lesions” (Devlin and Watkins, 2007). Still after 2 decades of human TMS, little is known about which neurons are the primary target and which processes are induced on the level of single neurons and neuronal networks, although the latter are often related to LTP or LTD (Huang et al., 2005). The very recently developed TMS-responsive, patterned neuronal cultures are an important step towards a thorough experimental analysis. We will combine theoretical, experimental, and clinical efforts to elucidate the cellular and synaptic mechanisms of TMS. Such an in-depth investigation and understanding is necessary to shift the present empirical design of diverse stimulation protocols towards a more systematic, rational design and assessment of clinical treatments with rTMS and transcranial direct current stimulation (tDCS).

TP1d figure1

Detection of [Ca2+] transients induced by magnetic stimulation (MS) A Fluorescently labelled neurons grown on 4 rings (radii of 14, 13, 12 and 11 mm). B Area marked in A during MS of the cultured neurons. C Relative fluorescence intensity ΔF/F averaged over the region 1. Dashed lines mark MS, numbers indicate the field in Tesla. Peaks of [Ca2+] reflect bursts of action potentials (APs) induced by MS and spontaneous APs. D MS-induced bursts grouped according to the MS strength. Neurons on rings with larger diameters have lower stimulus thresholds. (Courtesy of Moses/Rotem)

Belongs to Group(s):
Clinical Neurophysiology, Synaptic physiology and biophysics

Is part of  Section 1 

Members working within this Project:
Paulus, Walter  
Neef, Andreas  

Selected Publication(s):

Rotem, A, Neef, A, Neef, NE, Agudelo-Toro, A, Rakhmilevitch, D, Paulus, W, and Moses, E (2014).
Solving the Orientation Specific Constraints in Transcranial Magnetic Stimulation by Rotating Fields
PLOS ONE 9(2):1--10.

Agudelo-Toro, A, and Neef, A (2013).
Computationally efficient simulation of electrical activity at cell membranes interacting with self-generated and externally imposed electric fields
Journal of Neural Engineering 10(026019):1-19.

Gamboa, OL, Antal, A, Moliadze, V, and Paulus, W (2010).
Simply longer is not better: reversal of theta burst after-effect with prolonged stimulation
Exp Brain Res 204:181-187 doi: 10.1007/s00221-010-2293-4.