"Why?" How Transcranial Magnetic Stimulation is Helping Those Afflicted with Depression Answer That Question.

Why should I get up? Why should I care? Why should I keep going? Many people suffering from depression ask themselves questions like this daily. Pharmaceutical research has provided astonishing drug applications that can alleviate depression related symptoms and allow for a relatively “normal” life. The issue is not only do these drugs come with side effects, but they also don’t work equally for everyone based on varying disorders. According to WHO, “more than 300 million people are affected……. At its worst, depression can lead to suicide. Close to 800,000 people die due to suicide every year. Suicide is the second leading cause of death in 15-29-year-olds.” ¹

What happens when you’ve tried every prescription under the sun from the all too often revolving door of doctors? Advancements in the study between neuronal tissue and electric fields has yielded positive results utilizing repeated Transcranial Magnetic Stimulation (rTMS). US News (link) recently featured a segment around “Food and Drug Administration approved rTMS as a treatment for major depression for patients who do not respond to at least one antidepressant medication in the current episode. A large clinical trial, funded by NIMH and published in 2010, found that 14 percent of depression patients achieved remission with rTMS compared to 5 percent with a placebo treatment. Camprodon adds that about 70 percent of those who improve with treatment are still better a year later.” ²

TMS Diagram

One of the immediate key attractors for treatment-resistant depressed patients looking at rTMS is that it’s non-invasive (compared to vagus nerve/deep brain stimulation). ³ In straight forward terms, TMS utilizes a magnetic field generator in varying coil arrangements near the scalp to deliver a pulse stimulation to the targeted region of the brain. Due to the irregularities of tissues shape the positioning is highly debated, however, deep TMS can reach up to 6in into the tissue to stimulate deeper layers of the motor cortex. ⁴

Now, this doesn’t mean all is perfect with rTMS. According to the Mayo Clinic the below are common and uncommon side effects:
Common

• Headache
• Scalp discomfort at the site of stimulation
• Tingling, spasms or twitching of facial muscles
• Lightheadedness

Uncommon

• Seizures
• Mania, particularly in people with bipolar disorder
• Hearing loss if there is inadequate ear protection during treatment

What is happening within the neuronal tissue that lets us take advantage of external magnetic stimuli? In the study titled, “Neuron matters: electric activation of neuronal tissue is dependent on the interaction between the neuron and the electric field,” Ye et al. investigated the basis for the cell-field interaction in a two-way process. “When a neuron is positioned inside an electric field, the electric field will induce a change in the resting membrane potential by superimposing an electrically-induced transmembrane potential (ITP). At the same time, the electric field can be perturbed and re-distributed by the cell. This cell-field interaction may play a significant role in the overall effects of stimulation. The redistributed field can cause secondary effects to neighboring cells by altering their geometrical pattern and amount of membrane polarization. Neurons excited by the externally-applied electric field can also affect neighboring cells by ephaptic interaction. Both aspects of the cell-field interaction depend on the biophysical properties of the neuronal tissue, including geometric and electrical attributes of the cells.”⁵ The geometric attributes for the cells are one of the keys to better understanding and applying TMS. Most models do not consider tissue inhomogeneity which ends up being a larger factor in real world applications. As computational modeling becomes more advanced, it will allow for greater outputs on mentioned limitation. 

Interaction between the biological tissue and the electric field which determines the overall polarization. (Ye et al)

Furthermore, the study mentioned the transmembrane potential via surface charges as (Delta)V or “secondary term.” While the study focused on the build-up charge on the surface via varying tissue conductivities, what was the role of temperature dependence for the computation modeling? Specifically, what are the outcomes of relative temperature fluctuations? The Goldman–Hodgkin–Katz (GHK) voltage equation focuses heavily ion permeability, yet also has a key portion for temperature dependence (T - in Kelvin).

GHK Equation Reference

There are still many unknowns related to TMS, yet we have managed to show significant and positive benefits thus far. The limitations are currently being studied to best determine positioning of the magnet as well as combining treatments with medications and therapy. ⁶ TMS as an alternative has the capability to change a life with a simple and relatively (compared to prescriptions) low cost for those suffering from depression disorders. So, why not?

Support and funding are the most critical factors to enable continuing research in these fields.
*Crisis prevention number for those in emotional or critical distress: (US) 1-800-273-8255

Sources:

1. Depression. World Health Organization. http://www.who.int/mediacentre/factsheets/fs369/en/. Published February 2017. Accessed December 13, 2017.         

2. Levine D. Can Transcranial Magnetic Stimulation Help With Depression? https://health.usnews.com/health-care/patient-advice/articles/2017-11-17/can-transcranial-magnetic-stimulation-help-with-depression. Published November 17, 2017. Accessed December 13, 2017.

3. Transcranial magnetic stimulation. Mayo Clinic. https://www.mayoclinic.org/tests-procedures/transcranial-magnetic-stimulation/details/risks/cmc-20163840. Published August 10, 2017. Accessed December 13, 2017.

4. Zangen A, Roth Y, Voller B, Hallett M. Transcranial magnetic stimulation of deep brain regions: evidence for efficacy of the H-Coil. Clinical Neurophysiology. 2005;116(4):775-779. doi:10.1016/j.clinph.2004.11.008.

5. Ye H, Steiger A. Neuron matters: electric activation of neuronal tissue is dependent on the interaction between the neuron and the electric field. Journal of NeuroEngineering and Rehabilitation. 2015;12(1). doi:10.1186/s12984-015-0061-1.

6. Brain Stimulation Therapies. National Institute of Mental Health. https://www.nimh.nih.gov/health/topics/brain-stimulation-therapies/brain-stimulation-therapies.shtml. Accessed December 13, 2017.