Transcranial pulsed ultrasound

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Transcranial pulsed ultrasound (TPU) uses low intensity, low frequency ultrasound (LILFU) to stimulate the brain. In 2002, Dr. Alexander Bystritsky first proposed the idea that this methodology contained therapeutic benefits. [1] Beginning in 2008, Dr. William Tyler and his research team from Arizona State University began an investigation and development of this alternative neuromodulation without the harmful effects and risks of invasive surgery. They discovered that this low-power ultrasound is able to stimulate high neuron activity which allows for the manipulation of the brain waves through an external source. Unlike deep brain stimulation or Vagus nerve stimulation, which use implants and electrical impulses, TPU is a noninvasive and focused procedure that does not require the implantation of electrodes that could damage the nervous tissue. Its use is applicable in the various fields including but not limited to medical and military science. Although this technology holds great potential to introducing new and beneficial alternatives to conventional brain manipulation, it is a relatively young science and has certain obstructions to its full development such as a lack of complete understanding and control of every safety measure. [2]

Contents

Research and applications

Most of the research as of 2010 revolved around projects to utilize TPU as a method of treating neural disorders and improving cognitive function. However, in 2012 Dr. Tyler also began research on ultrasound's potential to stopping seizures. [3] Dr. Tyler and his team still continue to improve their knowledge of brain stimulation therapy and hope to provide a strong foundation in the implementation of such methods. [4]

Medical field

Scientists continue to test a variety of mammals such as humans, monkeys [5] and mice on positively affecting the treatment of epilepsy, Parkinson's disease, chronic pain, coma, dystonia, psychoses and depression by applying safe, low-intensity, TPU. Because the potential for this technology covers a wide variety of benefits, continued research into its safety and efficacy is expected to accelerate its integration into standard medical practice. [2]

Military

Defense Advanced Research Projects Agency (DARPA) is undergoing research to develop a helmet that could control the mental stress of soldiers through the use of TPU. It could have the potential to moderate a soldier's stress and anxiety levels. [6] Sound waves would target specific areas of the brain to stimulate activity in regions only a few cubic millimeters in size. This would allow them to target very specific areas of the brain with great accuracy and without inflicting damage to its surroundings. A prototype of this device is currently being worked upon to better the ability and potential of soldiers. [7]

Testing

Conventional ultrasound used for anatomical analysis typically uses a wave frequency of about 20 MHz to penetrate the bodily tissue and produce images. In comparison, the low frequency of TPU has a sub-thermal exposure of about 5.7 MHz. By significantly reducing the wave frequency, excitable tissue can be manipulated without overexposure or detectable damage. Scientists have discovered that focusing on targeted brain regions in animals has been proven to alter their behavior, their cells' electrical properties (electrophysiology), and their synaptic plasticity, which is essentially the neuron's ability to function. [1]

For instance, when focused on the motor cortex of mice, TPU has been shown to induce paw movements without changing the structure or function of that area of the brain. This proves that this method is capable of controlling brain activity at a high cognitive level. It is clear that shorter waves are able to activate neuron activity while longer waves inhibit it. However, the mechanism responsible for this reaction is yet to be discovered. A recent leading hypothesis is the mechanical manipulation of stretch-sensitive membranes actually stimulates certain voltage-gated ion channels, such as sodium or calcium, thus modulating neuronal activity. [1]

Limitations

Clinical trials have been used to determine any outstanding harmful effects. Although no subjects have displayed long-term neurological abnormalities as a result of these tests, this is a relatively new procedure and has not been studied enough to predict long term side effects. Even though it is a safer alternative to surgery because it is non-invasive, ultrasound always holds the potential to unintentionally disarrange the neurons in a harmful way and cause minor hemorrhages after long-term exposure. [8]

Therapeutic benefits

Opposing high-frequency ultrasound, LILFU holds the following benefits: lower absorption in tissue, greater physical penetration depth in tissue, stronger particle deflections, significantly better acoustic penetration and power in bone, greater influence in kinetic effects, immediate/short-term effect results, longer/persistent effects after procedure and a higher degree of patient safety. [9]

There has been evidence provided for ultrasound neuromodulation's potential in treating chronic pain and similar conditions. After 31 patients with chronic pain had 8 MHz unfocused transcranial ultrasound stimulation targeted to the posterior frontal cortex in a double-blind, sham-controlled study, they reported feeling in a better mood 10 to 40 minutes after having received the treatment. Due to time constraints, these tests are not necessarily extensive enough to provide conclusive evidence in regard to the treatment's effect on general mental wellbeing. [10]

Related Research Articles

<span class="mw-page-title-main">Ultrasound</span> Sound waves with frequencies above the human hearing range

Ultrasound is sound with frequencies greater than 20 kilohertz. This frequency is the approximate upper audible limit of human hearing in healthy young adults. The physical principles of acoustic waves apply to any frequency range, including ultrasound. Ultrasonic devices operate with frequencies from 20 kHz up to several gigahertz.

<span class="mw-page-title-main">Transcranial magnetic stimulation</span> Brain stimulation using magnetic fields

Transcranial magnetic stimulation (TMS) is a noninvasive form of brain stimulation in which a changing magnetic field is used to induce an electric current at a specific area of the brain through electromagnetic induction. An electric pulse generator, or stimulator, is connected to a magnetic coil connected to the scalp. The stimulator generates a changing electric current within the coil which creates a varying magnetic field, inducing a current within a region in the brain itself.

<span class="mw-page-title-main">Sonic weapon</span> Weapon that uses soundwaves against people

Sonic and ultrasonic weapons (USW) are weapons of various types that use sound to injure or incapacitate an opponent. Some sonic weapons make a focused beam of sound or of ultrasound; others produce an area field of sound. As of 2023 military and police forces make some limited use of sonic weapons.

Neurotechnology encompasses any method or electronic device which interfaces with the nervous system to monitor or modulate neural activity.

Neural engineering is a discipline within biomedical engineering that uses engineering techniques to understand, repair, replace, or enhance neural systems. Neural engineers are uniquely qualified to solve design problems at the interface of living neural tissue and non-living constructs.

Bioelectromagnetics, also known as bioelectromagnetism, is the study of the interaction between electromagnetic fields and biological entities. Areas of study include electromagnetic fields produced by living cells, tissues or organisms, the effects of man-made sources of electromagnetic fields like mobile phones, and the application of electromagnetic radiation toward therapies for the treatment of various conditions.

<span class="mw-page-title-main">Transcranial Doppler</span>

Transcranial Doppler (TCD) and transcranial color Doppler (TCCD) are types of Doppler ultrasonography that measure the velocity of blood flow through the brain's blood vessels by measuring the echoes of ultrasound waves moving transcranially. These modes of medical imaging conduct a spectral analysis of the acoustic signals they receive and can therefore be classified as methods of active acoustocerebrography. They are used as tests to help diagnose emboli, stenosis, vasospasm from a subarachnoid hemorrhage, and other problems. These relatively quick and inexpensive tests are growing in popularity. The tests are effective for detecting sickle cell disease, ischemic cerebrovascular disease, subarachnoid hemorrhage, arteriovenous malformations, and cerebral circulatory arrest. The tests are possibly useful for perioperative monitoring and meningeal infection. The equipment used for these tests is becoming increasingly portable, making it possible for a clinician to travel to a hospital, to a doctor's office, or to a nursing home for both inpatient and outpatient studies. The tests are often used in conjunction with other tests such as MRI, MRA, carotid duplex ultrasound and CT scans. The tests are also used for research in cognitive neuroscience.

Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (GPCRs) to initiate a second messenger signaling cascade that induces a broad, long-lasting signal. This modulation can last for hundreds of milliseconds to several minutes. Some of the effects of neuromodulators include: altering intrinsic firing activity, increasing or decreasing voltage-dependent currents, altering synaptic efficacy, increasing bursting activity and reconfigurating synaptic connectivity.

<span class="mw-page-title-main">Transcranial direct-current stimulation</span> Technique of brain electric stimulation therapy

Transcranial direct current stimulation (tDCS) is a form of neuromodulation that uses constant, low direct current delivered via electrodes on the head. It was originally developed to help patients with brain injuries or neuropsychiatric conditions such as major depressive disorder. It can be contrasted with cranial electrotherapy stimulation, which generally uses alternating current the same way, as well as transcranial magnetic stimulation.

Low-intensity pulsed ultrasound (LIPUS) is a technology that can be used for therapeutic purposes. It exploits low intensity and pulsed mechanical waves in order to induce regenerative and anti-inflammatory effects on biological tissues, such as bone, cartilage, and tendon. Even if the real mechanism underlying its effectiveness has not been understood yet, it is plausible that the treatment relies on non-thermal phenomena, such as microbubbles and microjets induced by cavitation, acoustic streaming, and mechanical stimulation.

Therapeutic ultrasound refers generally to any type of ultrasonic procedure that uses ultrasound for therapeutic benefit. Physiotherapeutic ultrasound was introduced into clinical practice in the 1950s, with lithotripsy introduced in the 1980s. Others are at various stages in transitioning from research to clinical use: HIFU, targeted ultrasound drug delivery, trans-dermal ultrasound drug delivery, ultrasound hemostasis, cancer therapy, and ultrasound assisted thrombolysis It may use focused ultrasound or unfocused ultrasound.

LILFU stands for low intensity, low frequency ultrasound. It is a new technique devised by the team of William J. Tyler from Arizona State University to manipulate neuronal circuits using transcranial pulsed ultrasound. This could make the need of invasive (surgical) neuromodulation for some treatments and therapies unnecessary.

Electroanalgesia is a form of analgesia, or pain relief, that uses electricity to ease pain. Electrical devices can be internal or external, at the site of pain (local) or delocalized throughout the whole body. It works by interfering with the electric currents of pain signals, inhibiting them from reaching the brain and inducing a response; different from traditional analgesics, such as opiates which mimic natural endorphins and NSAIDs that help relieve inflammation and stop pain at the source. Electroanalgesia has a lower addictive potential and poses less health threats to the general public, but can cause serious health problems, even death, in people with other electrical devices such as pacemakers or internal hearing aids, or with heart problems.

Neurostimulation is the purposeful modulation of the nervous system's activity using invasive or non-invasive means. Neurostimulation usually refers to the electromagnetic approaches to neuromodulation.

Neuromodulation is "the alteration of nerve activity through targeted delivery of a stimulus, such as electrical stimulation or chemical agents, to specific neurological sites in the body". It is carried out to normalize – or modulate – nervous tissue function. Neuromodulation is an evolving therapy that can involve a range of electromagnetic stimuli such as a magnetic field (rTMS), an electric current, or a drug instilled directly in the subdural space. Emerging applications involve targeted introduction of genes or gene regulators and light (optogenetics), and by 2014, these had been at minimum demonstrated in mammalian models, or first-in-human data had been acquired. The most clinical experience has been with electrical stimulation.

Magnetogenetics is a medical research technique whereby magnetic fields are used to affect cell function.

Transcranial random noise stimulation (tRNS) is a non-invasive brain stimulation technique and a form of transcranial electrical stimulation (tES). Terney et al from Göttingen University was the first group to apply tRNS in humans in 2008. They showed that by using an alternate current along with random amplitude and frequency in healthy subjects, the motor cortex excitability increased for up to 60 minutes after 10 minutes of stimulation. The study included all the frequencies up to half of the sampling rate i.e. 640 Hz, however the positive effect was limited only to higher frequencies. Although tRNS has shown positive effects in various studies the optimal parameters, as well as the potential clinical effects of this technique, remain unclear.

Non-invasive cerebellar stimulation is the application of non-invasive neurostimulation techniques on the cerebellum to modify its electrical activity. Techniques such as transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) can be used. The cerebellum is a high potential target for neuromodulation of neurological and psychiatric disorders due to the high density of neurons in its superficial layer, its electrical properties, and its participation in numerous closed-loop circuits involved in motor, cognitive, and emotional functions.

Neural dust is a hypothetical class of nanometer-sized devices operated as wirelessly powered nerve sensors; it is a type of brain–computer interface. The sensors may be used to study, monitor, or control the nerves and muscles and to remotely monitor neural activity. In practice, a medical treatment could introduce thousands of neural dust devices into human brains. The term is derived from "smart dust", as the sensors used as neural dust may also be defined by this concept.

<span class="mw-page-title-main">Functional ultrasound imaging</span> Ultrasound technique

Functional ultrasound imaging (fUS) is a medical ultrasound imaging technique of detecting or measuring changes in neural activities or metabolism, for example, the loci of brain activity, typically through measuring blood flow or hemodynamic changes. The method can be seen as an extension of Doppler imaging.

References

  1. 1 2 3 Hameroff, Stewart (2013). "Transcranial ultrasound (TUS) effects on mental states: A pilot study" (PDF). Brain Stimulation. 6 (3). Elsevier: 409–15. doi:10.1016/j.brs.2012.05.002. PMID   22664271. S2CID   206354818. Archived from the original (PDF) on 22 March 2013. Retrieved 25 October 2013.
  2. 1 2 "Ultrasound Shown To Exert Remote Control Of Brain Circuits". ScienceDaily. Brain Circuits. Retrieved 23 October 2013.
  3. ↑ Tyler, William. "Our Research in the News". Tyler Laboratory. Retrieved 10 November 2013.
  4. ↑ Tyler, William. "Research Program Summary". The Virginia Tech Carilion School of Medicine and Research Institute. Archived from the original on 3 November 2013. Retrieved 23 October 2013.
  5. ↑ Deffieux, T., Younan, Y., Wattiez, N., Tanter, M., Pouget, P., & Aubry, J. F. (2013). Low-intensity focused ultrasound modulates monkey visuomotor behavior. Current Biology, 23(23), 2430-2433
  6. ↑ Dillow, Clay (10 September 2010). "DARPA Wants to Install Transcranial Ultrasonic Mind Control Devices in Soldiers' Helmets". Popular Science. Bonnier Corporation. Retrieved 21 February 2016.
  7. ↑ Tyler, Dr. William J. "Remote Control of Brain Activity Using Ultrasound". Armed with Science. U.S. Defense Department. Retrieved 21 February 2016.
  8. ↑ Daffertshofer, M. (2005). "Transcranial low-frequency ultrasound-mediated thrombolysis in brain ischemia: increased risk of hemorrhage with combined ultrasound and tissue plasminogen activator: results of a phase II clinical trial". Stroke. 36 (7): 1441–6. doi: 10.1161/01.STR.0000170707.86793.1a . PMID   15947262.
  9. ↑ "Why low-frequency Ultrasound?". UltraPuls. Retrieved 13 November 2013.
  10. ↑ Zhang, T.; Pan, N.; Wang, Y.; Liu, C.; Hu, S. (2021). "Transcranial Focused Ultrasound Neuromodulation: A Review of the Excitatory and Inhibitory Effects on Brain Activity in Human and Animals". Frontiers in Human Neuroscience. 15. Open Access Publishing. doi: 10.3389/fnhum.2021.749162 . PMC   8507972 . PMID   34650419.
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