Modern Electric Brain Stimulation

A patient strapped down on a hospital bed, fighting the bandages; several people in white coats led by a crazy scientist, sticking electrodes on the patient’s head and turning the current up until there is nothing but screams! This might be the first thing coming to mind when hearing ‘electric brain stimulation’. However, modern brain stimulation is quite different.

Scientists can stimulate the brain transcranially, from outside the head, or intracranially, from within. Three major transcranial stimulation methods are used: Transcranial Magnetic Stimulation (TMS), where a coil held over the head induces current electromagnetically; transcranial Direct or Alternating Current Stimulation (tDCS and tACS), where electrodes attached to the head induce low current directly; and Electroconvulsive Therapy (ECT), where electrodes induce a stronger current. Intracranial stimulation requires electrodes to be surgically placed on top of or inside the cortex to stimulate a specific region of the brain.

Tingling and tickling

The techniques TMS, tDCS and tACS induce low voltage current of around 1mA to 6mA in the brain ⁽¹⁾Peterchev, A. V., Wagner, T. A., Miranda, P. C., Nitsche, M. A., Paulus, W., Lisanby, S. H., … & Bikson, M. (2012). Fundamentals of transcranial electric and magnetic stimulation dose: definition, selection, and reporting practices. Brain stimulation, 5(4), 435-453.. According to tDCS participants, stimulation can cause tingling, itching, burning or painful sensations, but the severity of such sensations has been rated low ⁽²⁾Kessler, S. K., Turkeltaub, P. E., Benson, J. G., & Hamilton, R. H. (2012). Differences in the experience of active and sham transcranial direct current stimulation. Brain stimulation, 5(2), 155-162.. Most commonly reported side effects during and after TMS are mild local pain or headache ⁽³⁾Taylor, R., Galvez, V., & Loo, C. (2018). Transcranial magnetic stimulation (TMS) safety: a practical guide for psychiatrists. Australasian Psychiatry, 26(2), 189-192.. However, participants also struggle with differentiating the control condition ⁽⁴⁾In tDCS, tACS and TMS experiments sham stimulation is used as a control condition. The difference between sham and real stimulation is that during sham the electric current is only ramped up for a short time, whereas it continues on the same level for a longer time during real stimulation. from the stimulated condition ⁽⁵⁾Mennemeier, M. S., Triggs, W. J., Chelette, K. C., Woods, A. J., Kimbrell, T. A., & Dornhoffer, J. L. (2009). Sham transcranial magnetic stimulation using electrical stimulation of the scalp. Brain stimulation, 2(3), 168-173., ⁽⁶⁾Palm, U., Reisinger, E., Keeser, D., Kuo, M. F., Pogarell, O., Leicht, G., … & Padberg, F. (2013). Evaluation of sham transcranial direct current stimulation for randomized, placebo-controlled clinical trials. Brain stimulation, 6(4), 690-695.. That indicates the workings of the nocebo effect – participants might expect negative outcomes which then really happen or worsen the symptoms ⁽⁷⁾Benedetti, F., Lanotte, M., Lopiano, L., & Colloca, L. (2007). When words are painful: unraveling the mechanisms of the nocebo effect. Neuroscience, 147(2), 260-271..

For the worst case, when no other therapy works, highly effective methods are ETC and intracranial stimulation. ETC is often used for severely depressed and suicidal, treatment-resistant patients. Here, stronger currents of around 800mA get induced, always under anesthesia, leading to an epileptic seizure. Although that sounds drastic, as a reference: the current in your power socket at home ranges from 5,000mA to 10,000mA. Different from the horror story described in the beginning, the procedure happens in agreement with the patient. Nobody is strapped down and forced. Although the list of possible side effects is long ⁽⁸⁾Datto, C. J. (2000). Side effects of electroconvulsive therapy. Depression and anxiety, 12(3), 130-134., the benefits of successfully treating major psychiatric conditions outweigh the side effects. Intracranial simulation can be located precisely onto a region of interest in the brain and requires weaker currents to treat, for example, tremors by pressing a button. A downside to this method is that electrodes, when left inside the brain, lose their functionality over time as tissue grows around them.

What does brain stimulation do?

The idea behind stimulating the brain is based on the ‘all or nothing’ way neurons work. Neurons either fire or they do not. In order to fire they need to exceed a threshold of ‘electric charge’ (ca. 65mV). This can be influenced in different ways by stimulating the brain ⁽⁹⁾Pelletier, S. J., & Cicchetti, F. (2015). Cellular and molecular mechanisms of action of transcranial direct current stimulation: evidence from in vitro and in vivo models. International Journal of Neuropsychopharmacology, 18(2), pyu047.. So far, scientists know that they can excite or inhibit neural activity with brain stimulation ⁽¹⁰⁾Romero, M. C., Davare, M., Armendariz, M., & Janssen, P. (2019). Neural effects of transcranial magnetic stimulation at the single-cell level. Nature communications, 10(1), 1-11.. However, the biochemical processes underlying brain stimulation are not yet fully understood ⁽¹¹⁾Pelletier, S. J., & Cicchetti, F. (2015). Cellular and molecular mechanisms of action of transcranial direct current stimulation: evidence from in vitro and in vivo models. International Journal of Neuropsychopharmacology, 18(2), pyu047.. 

One approach to look at the underlying biochemical mechanisms of tDCS is to measure neurotransmitter concentrations. When exciting brain regions electrically, we can expect excitatory neurotransmitter concentrations to increase and consequently brain chemistry to change. However, recent studies showed mixed and incongruent evidence for specific neurotransmitters ⁽¹²⁾Hone-Blanchet, A., Edden, R. A., & Fecteau, S. (2016). Online effects of transcranial direct current stimulation in real time on human prefrontal and striatal metabolites. Biological psychiatry, 80(6), 432-438., ⁽¹³⁾Clark, V. P., Coffman, B. A., Trumbo, M. C., & Gasparovic, C. (2011). Transcranial direct current stimulation (tDCS) produces localized and specific alterations in neurochemistry: a 1H magnetic resonance spectroscopy study. Neuroscience letters, 500(1), 67-71., ⁽¹⁴⁾Auvichayapat, P., Keeratitanont, K., Janyachareon, T., & Auvichayapat, N. (2018). The effects of transcranial direct current stimulation on metabolite changes at the anterior cingulate cortex in neuropathic pain: a pilot study. Journal of Pain Research, 11, 2301., ⁽¹⁵⁾Psomiades, M., Mondino, M., Poulet, E., Haesebaert, F., Suaud-Chagny, M. F., & Brunelin, J. (2017). Fronto-temporal transcranial direct-current stimulation reduces auditory verbal hallucinations and n-acetylaspartate-glutamate level in the left temporoparietal junction in patients with schizophrenia. Brain Stimulation, 2(10), 517-518., ⁽¹⁶⁾Ryan, K., Wawrzyn, K., Gati, J. S., Chronik, B. A., Wong, D., Duggal, N., & Bartha, R. (2018). 1H MR spectroscopy of the motor cortex immediately following transcranial direct current stimulation at 7 Tesla. PLoS One, 13(8), e0198053., ⁽¹⁷⁾Marquardt, L., Kusztrits, I., Craven, A. R., Hugdahl, K., Specht, K., & Hirnstein, M. (2020). A multimodal study of the effects of tDCS on dorsolateral prefrontal and temporo‐parietal areas during dichotic listening. European Journal of Neuroscience., ⁽¹⁸⁾Dwyer, G. E., Craven, A. R., Hirnstein, M., Kompus, K., Assmus, J., Ersland, L., … & Grüner, R. (2019). No effects of anodal tDCS on local GABA and Glx levels in the left posterior superior temporal gyrus. Frontiers in neurology, 9, 1145.. Thus, our understanding of the precise mechanisms involved in brain stimulation leaves something to be desired.

What is brain stimulation useful for? 

Brain stimulation can also help to cross-validate findings on the localisation of functions in the brain and determine when they are involved. After finding evidence for the localisation of a function, such as movement-control leading to activations in the motor cortex, it can be tested whether this region is solely responsible for the function by inhibiting it during a task which recruits neurons from the region. The timing here is crucial, as brain regions work together in perfectly timed processes. Another option is to use TMS to stimulate the region in the motor cortex responsible for hand movement. Oh dear! It moves without the participant having any control about it! That can give valuable insights into what to cut away and what to better leave intact when planning and executing surgery to remove tumours. 

The recent years’ research has also contributed immensely to the understanding that brain stimulation has strong potential to treat or assist the treatment of various conditions. The strongest effects could be found for the effectiveness of TMS in treating depression, chronic pain and motor stroke ⁽¹⁹⁾Lefaucheur, J. P., Aleman, A., Baeken, C., Benninger, D. H., Brunelin, J., Di Lazzaro, V., … & Jääskeläinen, S. K. (2020). Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): an update (2014–2018). Clinical neurophysiology, 131(2), 474-528.. tDCS treatments are likely to be effective in treating depression, addiction (especially craving), and also chronic pain ⁽²⁰⁾Lefaucheur, J. P., Antal, A., Ayache, S. S., Benninger, D. H., Brunelin, J., Cogiamanian, F., … & Marangolo, P. (2017). Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS). Clinical Neurophysiology, 128(1), 56-92..

Although brain stimulation is useful in different therapeutic contexts, knowledge about its uses as a neuroenhancer—to boost a healthy person’s cognitive abilities and hence performance—is much more sparse. A range of studies suggest that TMS ⁽²¹⁾Kim, T. D., Hong, G., Kim, J., & Yoon, S. (2019). Cognitive enhancement in neurological and psychiatric disorders using transcranial magnetic stimulation (TMS): a review of modalities, potential mechanisms and future implications. Experimental Neurobiology, 28(1), 1. and tDCS ⁽²²⁾Antal, A. (2016). Neuroenhancement: Scientific, ethical and legal issues of lay tDCS for home-use. Clinical Neurophysiology, 127(3), e21. act as neuroenhancers. Most studies on TMS as a neuroenhancer found effects on short term memory and processing skills such as selective attention – the ability to inhibit what is unimportant and focus on the important ⁽²³⁾Kim, T. D., Hong, G., Kim, J., & Yoon, S. (2019). Cognitive enhancement in neurological and psychiatric disorders using transcranial magnetic stimulation (TMS): a review of modalities, potential mechanisms and future implications. Experimental Neurobiology, 28(1), 1.. However, single-study sample sizes are low and the methods incongruent between studies. The method is also strongly discussed when it comes to applications outside the clinical and research context ⁽²⁴⁾Antal, A. (2016). Neuroenhancement: Scientific, ethical and legal issues of lay tDCS for home-use. Clinical Neurophysiology, 127(3), e21..

Most importantly, brain stimulation is a valuable research tool to understand the intricacies of the brain and can be valuable in clinical contexts by reducing costs, consequences and duration of different illnesses ⁽²⁵⁾Clark, V. P., & Parasuraman, R. (2014). Neuroenhancement: enhancing brain and mind in health and in disease. Neuroimage. 85(3), 889-894.. The methods can hence help not only to better understand the brain but also to improve the lives of those suffering from different conditions. Thus, contrary to the image of causing shackled patients to struggle, electric brain stimulation can help alleviate their suffering and free them from the shackles of their illness.