The enhancement of human cognitive processes has long been a focus of scientific discovery. Progress in technology and research, has lead to non-invasive brain stimulation therapies playing increasingly important roles in improving neuroplasticity, brain performance, and neuromodulation.

What is non-invasive brain stimulation?

Non-invasive brain stimulation is defined as the delivery of energy through the cranium to the brain, to stimulate or improve its activity.

Over the past decade, new discoveries in neuroscience have led to a better understanding of the brain’s mechanisms and how different forms of energy can influence changes within the brain.

In this blogpost, the different energy sources used for brain stimulation will be examined along with their applications.

What are the different types of brain stimulation technologies?

Brain stimulation technologies involve activating or inhibiting the brain directly with:

  • Electricity (transcranial direct stimulation, tDCS)
  • Magnetic fields (transcranial magnetic stimulation, tMS)
  • Electromagnetic radiation within the 600-1100nm range (photobiomodulation, PBM)

These different types of energy sources produce different outcomes.

Transcranial direct current stimulation (tDCS)

Transcranial direct stimulation involves the use of weak currents of electricity delivered via electrodes on the head. It was originally developed to help patients with brain injuries or neuropsychiatric conditions such as major depressive disorder.

tDCS works by applying a positive (anodal) or negative (cathodal) current via electrodes to an area. During stimulation, current flows between the electrodes, passing through the brain to complete the circuit. The position of the anode and cathode electrodes on the head is used to set how current flows to specific brain regions.[1]

Mechanisms

It is hypothesized that anodal stimulation increases neuronal excitability, while cathodal stimulation produces the opposite effect. [2] However, the relationship between the stimulation and neural response is not dependent on just the electrode type but also the length and strength of the stimulation applied through it.[3] Neurons throughout the cortex are not modulated in a homogenous manner. Neurons in deep cortical layers are often deactivated by anodal stimulation and activated by cathodal stimulation.[4] Given the complexity of the brain’s electrical signaling, inconsistent outcomes of transcranial direct current stimulation (tDCS) may originate from the anatomical differences among individuals.[5]

Technology

tDCS devices delivers low electric current to the scalp through electrodes placed on the head. A fixed current between 1 and 2 mA is typically applied. There is usually a control panel that allows you to program the device (to set the duration and intensity of stimulation).

transcranial direct current stimulation technology

Figure 1. This figure denotes transcranial direct current stimulation technology delivering continuous low current stimulation by applying a positive (anodal) or negative (cathodal) current via paired electrodes over the scalp.

Set-up

A standard tDCS set-up uses a target and a reference electrode. First, the desired locations of where the electrodes will be positioned are determined. Saline solution, conductive paste or EEG gel are used to affix the electrodes to the scalp and distribute the current. The participant’s hair should be parted to ensure good contact between scalp and electrode. Electrodes are then attached to the stimulator using wires connected to corresponding anodal/cathodal ports.

Outcomes

Research shows increasing evidence for tDCS as a treatment for depression.[6, 7, 8] There is mixed evidence about whether tDCS is useful for cognitive enhancement in healthy people. There is no strong evidence that tDCS is useful for memory deficits in Parkinson’s disease and Alzheimer’s disease.

Transcranial magnetic stimulation (TMS)

Transcranial magnetic stimulation (TMS) is a non-invasive procedure that uses magnetic fields generated through electrical currents passing through an electromagnetic coil. The magnetic field then delivers electrical current into the brain through induction stimulate nerve cells in the brain.

Mechanisms

At present, the mechanisms of TMS is not well understood. What is known is the current produced is above the threshold needed to make a neuron activate. When the coil is placed on the motor cortex, TMS makes the cells in the motor cortex active, enough to make a finger twitch.

Some studies have proposed the activation of neurotransmitter systems as a working mechanistic model.[9]

Technology

TMS equipment usually consists of a small electromagnetic coil and a computer which controls the frequency and power output.

TMS machine

Figure 2: TMS machines deliver electrical currents into the brain through induction from an electromagnetic coil.

Transcranial Photobiomodulation (tPBM)

Transcranial photobiomodulation or brain photobiomodulation is a newer field of brain stimulation that uses LEDs or lasers to deliver light energy in the near-infrared to far-infrared (800 – 1000+ nm) wavelengths to the brain.

Mechanisms

Brain photobiomodulation (PBM) utilizes red to near-infrared (NIR) photons to stimulate the cytochrome c oxidase enzyme of the mitochondrial respiratory chain. Cytochrome c oxidase is receptive to light energy. This results in an increase in ATP synthesis, leading to the generation of more cellular energy. Additionally, photon absorption by ion channels results in release of Ca2+ which leads to the activation of transcription factors and gene expression.

  • Published study (May 2022) using the Vielight Neuro Alpha on how neurons and cellular components such as microtubules and tubulin respond to near-infrared PBM.
  • Published study (April 2019) using the Vielight Neuro Gamma on how near-infrared PBM could positively cognition, memory consolidation and mental energy.

light energy and vielight iPBM

Figure 3 Mechanisms of photobiomodulation

Therapeutic Outcomes of Brain Photobiomodulation: CCO upregulation

The absorption of red to NIR photons by mitochondria CCO triggers a series of cellular and physiological effects occur in the brain, also known as CCO upregulation.

CCO upregulation leads to:

  • A small increase in reactive oxygen species (ROS), which activate mitochondrial signaling pathways linked to neuroprotection.[13]
  • An increase in nitric oxide (NO) which stimulate vasodilation and cerebral blood flow.[14]
  • An increase in ATP production[15]
  • Combined, these effects trigger and improve the activation of signaling pathways and transcription factors that modulate the long-term expression of various proteins and metabolic pathways in the brain.[6] Additionally, electrophysiological effects on the human brain have also been demonstrated by PBM in older people.[16, 17]

Metabolic effects and brain oxygenation

The metabolic effects of PBM in the elderly have been shown to increase cerebral blood flow (CBF) due to the increase in CCO activity, leading to an increase in brain oxygenation. Photobiomodulation of the prefrontal cortex was able to increase the resting-state EEG alpha, beta and gamma power, and more efficient prefrontal fMRI response, facilitating cognitive processing in the elderly. [18] Additionally, photobiomodulation of the Default Mode Network (DMN) has also been shown to increase cerebral perfusion due to an increase in mitochondrial activity. [19]

Brain PBM and anti-inflammatory effects

In addition to the above findings, PBM may be a promising strategy for improving aging brains because of its anti-inflammatory effects. [20, 21]

Brain PBM leads to a reduction in neuronal excitotoxicity

In 2022, researchers from the University of Alberta published a multi-layered study investigating the way that living cells, cellular structures, and components such as microtubules and tubulin respond to near-infrared photobiomodulation (NIR PBM) using the Vielight Neuro Alpha.

Their study showed that PBM balances excitatory stimulation with inhibition, indicating that PBM may reduce excitotoxicity which is relevant to the maintenance of a healthy brain. This study also showed that low-intensity PBM upregulates mitochondrial potential and improves physiological brain functions impaired due to trauma or neurodegeneration. [22]

Brain PBM increases cerebral vascularity and oxygenation

Aging is accompanied by changes in tissue structure, often resulting in functional decline. The blood vessels within the brain are no exception. As one ages, a decrease in blood flow to the brain is caused by a loss of cerebral vascularity, leading to cognitive decline when neurons cannot obtain sufficient oxygen.[23] Brain photobiomodulation has also been shown to increase cerebral blood flow due to the vasodilation that occurs after the release of nitric oxide.[24]

brain photobiomodulation benefits

Figure 4 Therapeutic outcomes of photobiomodulation

Technology

Brain photobiomodulation devices consist of either headsets or helmets that position LEDs or laser diodes over the cranium.

The diodes need to generate enough power with proper wavelengths to penetrate the skull. There’s little utility in generating a lot of total power if none of it reaches the brain.

There are several aspects of brain photobiomodulation devices that users need to be aware of.

Penetration

Figure 5 Penetration of Neuro LEDs through the cranium and nasal area.

Brain photobiomodulation devices should be designed for maximum transmission of light energy safely without generating heat.

That can be accomplished through maximizing contact with the scalp. For example, the Vielight Neuro’s headset’s LED modules were designed to maximize contact with the scalp. Additionally, the headset design ensures that heat isn’t trapped.

Wavelength

The accepted wavelength range for brain photobiomodulation is within the NIR to far infrared range.

The near infrared (NIR) range in the electromagnetic spectrum has a theoretical maximum depth of penetration in tissue.


Figure 6 The optical window
Image source: Wang, Erica & Kaur, Ramanjot & Fierro, Manuel & Austin, Evan & Jones, Linda & Jagdeo, Jared. (2019).
Safety and penetration of light into the brain. 10.1016/B978-0-12-815305-5.00005-1.

Visible light (wavelength 400 to 700 nm) is substantially absorbed by hemoglobin and other organic matter. On the other hand, absorption by water increases at wavelengths longer than near infrared light (1000+nm). This implies that wavelengths outside of the near-infrared window cannot easily penetrate deeply through tissue.

References

  1. Thair H, Holloway AL, Newport R, Smith AD. Transcranial Direct Current Stimulation (tDCS): A Beginner’s Guide for Design and Implementation. Front Neurosci. 2017;11:641. Published 2017 Nov 22. doi:10.3389/fnins.2017.00641
  2. Cambiaghi M, Velikova S, Gonzalez-Rosa JJ, Cursi M, Comi G, Leocani L. (2010). Brain transcranial direct current stimulation modulates motor excitability in mice. Eur J Neurosci 31:704–709.
  3. Roche, M. Geiger, B. Bussel, Mechanisms underlying transcranial direct current stimulation in rehabilitation, Annals of Physical and Rehabilitation Medicine, Volume 58, Issue 4, https://doi.org/10.1016/j.rehab.2015.04.009
  4. P. Purpura, J.G. McMurtry, Intracellular activities and evoked potential changes during polarization of motor cortex, J Neurophysiol, 28 (1965), pp. 166-185
  5. Kim JH, Kim DW, Chang WH, Kim YH, Im CH. Inconsistent outcomes of transcranial direct current stimulation (tDCS) may be originated from the anatomical differences among individuals: a simulation study using individual MRI data. Annu Int Conf IEEE Eng Med Biol Soc. 2013;2013:823-5. doi: 10.1109/EMBC.2013.6609627. PMID: 24109814.
  6. Brunoni AR, Moffa AH, Fregni F, Palm U, Padberg F, Blumberger DM, Daskalakis ZJ, Bennabi D, Haffen E, Alonzo A, Loo CK (2016). “Transcranial direct current stimulation for acute major depressive episodes: meta-analysis of individual patient data”.  doi:1192/bjp.bp.115.164715.
  1. Julian Mutz, Vijeinika Vipulananthan, Ben Carter, René Hurlemann, Cynthia H Y Fu, Allan H Young (2019). “Comparative efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults: systematic review and network meta-analysis”. BMJ. 364: l1079. doi:10.1136/bmj.l1079
  2. “Transcranial direct current stimulation (tDCS) for depression”. NICE. August 2015. Retrieved 10 November 2015.
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