Rotational field TMS for depression
Our lab has developed extensive expertise in living neuronal networks and in understanding how neurons respond to different forms of physical stimulation. These include externally applied electric and magnetic fields, mechanical perturbation and ultrasound.
Transcranial Magnetic Stimulation (TMS) is often used in treatment resistant depression, but currently available TMS coils produce magnetic and electric fields with fixed direction. As a result, only the fraction of neurons in the targeted brain area that are aligned with the field are stimulated. We invented a novel TMS method that electronically rotates the stimulating field (rfTMS) and enables simultaneous activation of many more neurons in various orientations. This is done using a cloverleaf array combining two perpendicular figure-8 coils whose induced fields are orthogonal at the hotspot. The coils are driven with biphasic pulses at a ¼-cycle phase offset. The induced field is the vector sum of the two channels, which sweeps the plane covering 270°. The rotating vector aligns with axons distributed across many directions, and has an increased chance of activating their neurons.
To test these concepts practically we embarked on a clinical trial. In collaboration with psychiatrists at the Geha Mental Health Center we studied the efficacy of rfTMS for major depressive disorder (MDD) targeting the medial prefrontal cortex (mPFC). We performed a four-week randomized double-blind feasibility study, evaluating safety and efficacy of rfTMS and comparing it to the well-established unidirectional TMS (udTMS). Patients with treatment-resistant MDD completed 4 weeks of stimulation (rfTMS n=8; udTMS n=4). rfTMS showed a significantly greater improvement in the depressive symptoms as reflected by the HDRS-17, and specifically with regard to suicidal ideation, compared to udTMS, despite limitation associated with a small sample size. Mean HDRS-17 improvement was 10.9 vs 3.8 - a relative reduction of 44% vs 14%. Remission was 3/8 vs 0/4. Suicidality HDRS reduction was at 1.1 vs 0 (out of a range of 0-4).
In light of the success of the clinical trial in alleviating symptoms of MDD, we now plan to introduce a significant improvement on the electronic rotation of the magnetic field, going from three-quarters of a cycle to a full cycle. This is done by two consecutive pulses, and has the potential to improve even further the efficacy of neuronal stimulation in areas with no dominant axonal direction. Since these directionally heterogeneous areas are common targets for intervention in brain disorders, we expect to achieve significant impact on treatment efficacy.
Efficacy of rotational field TMS in major depressive disorder – A pilot study
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Solving the Orientation Specific Constraints in Transcranial Magnetic Stimulation by Rotating Fields
Rotem A., Neef A., Neef N. E., Agudelo-Toro A., Rakhmilevitch D., Paulus W. & Moses E.
(2014) PLoS ONE. 9, 2, e86794.
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