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New Technology and Development Trends of Non-invasive Neuromodulation

Brain neuromodulation refers to the technology of delivering chemical substances or physical energy such as electricity, magnetism, sound, and light to specific neural tissues in the body through invasive or non-invasive techniques to modulate the activity of neurons and the neural networks they are connected to, and ultimately to cause specific brain function changes. Through different stimulation methods, neuromodulation can trigger rapid, small-scale functional changes in the brain's neural tissues, as well as uninterrupted changes in neuronal function and neural loop connections. Therefore, neuromodulation is an important tool that can reveal the causal relationship between the brain in cognition and behavior and analyze the brain function by affecting the brain activity.

TMS. (Shirota, Yuichiro, et al., 2024)Fig. 1 A TMS stimulator.1

To date, a large number of invasive and non-invasive neuromodulation techniques have been developed both domestically and internationally. Creative Biolabs introduces new non-invasive neuromodulation techniques and trends. As a partner, we offer the following related services to help accelerate the progress of your program.

Our Services Descriptions
Mechanism of Action (MOA) Studies Creative Biolabs offers a full suite of services to help pharmaceutical and biotech companies accelerate their preclinical discovery and development. Based on our extensive experience and advanced platforms, we now provide tailored mechanism of action (MOA) study services for our clients all over the world.
Neurological Imaging Two of the most commonly used functional neuroimaging techniques are PET and SPECT. Another method commonly used for the study of brain fMRI. Also using the principles of TMS and MRI, it is possible to study the neurochemistry of the brain in vivo.
In Vitro Study for Neuroscience In vitro studies in neuroscience play a crucial role in neurological research. Our commitment to excellence has driven us to develop high-end in vitro services, revolutionizing the field of neuroscience and paving the way for groundbreaking discoveries.

New Non-invasive Neuromodulation Technology - Transcranial Magnetic Stimulation

Due to the high risk of invasive neuromodulation techniques, non-invasive neuromodulation techniques have become the most important research and clinical application techniques in the field of brain science.

Transcranial magnetic stimulation (TMS) is a kind of non-invasive neuromodulation technology, which is based on Faraday's electromagnetic induction phenomenon and consists of a magnetic stimulator outputting a time-varying magnetic field through a coil, which penetrates into the scalp, skull and cerebrospinal fluid and generates an induced current in the target area of the intracranial brain tissues, which can cause nerve cells to generate action potentials and change the excitability or excitability of the brain cells when the intensity of the current reaches or exceeds the threshold of the stimulation. When the current intensity reaches or exceeds the stimulation threshold, it can cause nerve cells to generate action potentials, change the excitatory or inhibitory neuron group activity, and then increase or decrease the excitability of the cerebral cortex.

TMS has the following advantages:

  • Non-invasive
  • Non-contact
  • Good safety
  • Small adverse reactions
  • Can penetrate the skull to directly stimulate the cerebral cortex
  • Good targeting

New Non-invasive Neuromodulation Technology - Transcranial Electrical Stimulation

Transcranial electrical stimulation (TES) is another non-invasive neurostimulation technique that is widely used today. TES delivers electric current through surface electrodes applied directly to the head, and is divided into:

Types Descriptions
Transcranial Direct Current Stimulation (tDCS) tDCS applies a weak direct current of 1 to 2 mA continuously to the scalp through 2 or more surface electrodes.
Transcranial Alternating Current Stimulation (tACS) tACS applies a sinusoidal current between the 2 electrodes, in which the direction and polarity of the current alternate according to a sinusoidal wave pattern, with the aim of modulating brain oscillations and cognitive functions and as a therapeutic technique for restoring cortical oscillations in neurological dysfunctions.
Transcranial Random Noise Stimulation (tRNS) Compared with tACS, tRNS is characterized by a wider frequency spectrum (0.1 to 640.0 Hz) and random noise distribution to cover the frequency range of neuronal oscillations in the brain.

As brain functional partitioning becomes more and more refined and precise, the need for non-invasive neuromodulation techniques for high spatial resolution brain nerve target stimulation is becoming more and more urgent when used for the study of brain cognitive neural mechanisms. In order to improve the spatial resolution and depth of stimulation of neural tissues in the human brain, researchers have developed new non-invasive neuromodulation techniques with higher spatial resolution.

New Non-invasive Neuromodulation Technology - Transcranial Ultrasound Stimulation and Transcranial Magneto-acoustic Stimulation

Transcranial ultrasound stimulation (TUS) utilizes ultrasound waves that can be focused on cortical and deep brain targets, with a spatial resolution of several cubic millimeters and a depth of focus of 5-7 cm below the scalp. At present, the effects of noninvasive ultrasound neuromodulation on humans, nonhuman primates, and small animals have been confirmed. At present, the effect of noninvasive ultrasound neuromodulation on human, non-human primate and small animal neuromodulation has been confirmed, but its neuromodulation principle and mechanism still need to carry out a large number of experimental studies on humans and animals, including its safety limit for human brain modulation, brain stimulation target area related to brain diseases, and stimulation parameters and modes that effectively modulate neuron plasticity in the brain.

Unlike TUS, which is formed by a single physical site, transcranial magneto-acoustic stimulation (TMAS) is another non-invasive neuromodulation technique that can realize highly focused stimulation in the deep brain, which is a composite stimulation technique formed by the coupling of acoustic and magnetic fields, and composite in the sense that the stimulation technology in the brain nerve target area is formed by the focused acoustic field and based on the magneto-acoustic coupling effect produced by the focused coupled electric field of the composite physical field stimulation, the principle is that the biological tissue contains electrically conductive particles, vibration in the ultrasonic action, vibration particles in the applied magnetic field by the Lorentz force to produce a coupled electric field.

This technique has been shown to improve synaptic plasticity in neurons and motor and memory abilities in experimental animals.

In addition, there are non-invasive neuromodulation techniques that indirectly affect neural activity in the target area through neural circuits or biological effects.

Types Descriptions
Transcutaneous auricular vagus nerve stimulation (taVNS) This technique activates the auricular branch of the vagus nerve by delivering electrical impulses to the epidermis of the ear to modulate brain physiology.
Transcranial near-infrared laser stimulation (tPBM) The technique directly irradiates the brain tissue through the skull by applying low-radiation (0.01-10.00 W/cm2) red light to near-infrared light (600-1,300 nm) to achieve neuroprotection and behavioral improvement. tPBM enhances the mitochondrial activity of neuronal cells.

Trends in Non-invasive Neuromodulation

With the continuous improvement and refinement of technical performance and stimulation modes, non-invasive neuromodulation technologies and devices such as TMS and TES provide strong technical support for in-depth investigation of the physiological basis and functional mechanism of neuromodulation, and continuous improvement of neuromodulation efficacy.

Therefore, real-time feedback adjustment of stimulation parameters according to the state of neural activity and synchronization of stimulation timing with the state of EEG signals to further enhance the temporal and spatial precision, localization, and targeting of noninvasive neuromodulation technology is an important direction for the development of noninvasive neuromodulation technology. The research of closed-loop control methods and techniques for real-time neuromodulation has become a trend.


  1. Shirota, Yuichiro, and Yoshikazu Ugawa. "Transcranial magnetic stimulation." Current Opinion in Behavioral Sciences 58 (2024): 101396.
For Research Use Only. Not For Clinical Use.
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