Geon How Ultrasound May Recover Consciousness MT

 

For more than a century, neural stimulation has been based on electrical methods. Although ultrasound was demonstrated to be a viable method nearly ninety years ago [E.N. Harvey, Am. J. Physiol., 91 (1929), pp. 284–290], the discovery was largely ignored. Only recently has researchers begun active investigations in this area (Tyler et al., 2008; Tufail et al., 2010; Kim et al., 2012; Menz et al., 2013; Mueller et al., 2014; Lee et al., 2015; Kamimura et al., 2016). In 2016, a UCLA team showed that ultrasound could recover a man's consciousness from coma by focusing on the thalamus (UCLA News). This remarkable result ushered in a new era of ultrasound applications, not only for the recovery of consciousness, but also for the treatment of traumatic brain injury, Alzheimer's disease and other neurodegenerative disorders.

Thalamus and Consciousness

The thalamus plays a pivotal role in consciousness. Most general anesthetics induce unconsciousness by acting on GABAA receptors to suppress neural activities in the thalamus. However, ketamine is a notable exception. It increases thalamic activity. The finding has baffled researchers for many years. Recently, more in-depth studies revealed that ketamine increases both gamma and theta oscillations, but reduces the alpha rhythms. The frontal-parietal connectivity in the alpha band is also reduced by ketamine (see General Anesthetics). These observations support the Alpha Hypothesis that consciousness arises from globally synchronized alpha oscillations (see The Origin of Consciousness).

Images

Figure 1. The thalamic nuclei. The lateral geniculate nucleus and pulvinar play a key role in the generation of synchronized alpha rhythms, and thus crucial for the emergence of consciousness. [Source: Wikipedia]

The alpha rhythm in the posterior regions (occipital, temporal and parietal lobes) may originate from the thalamus (Schreckenberger et al., 2004), specifically the lateral geniculate nucleus (Hughes et al., 2004) and pulvinar (Saalmann et al., 2012). Neuronal activation in these two areas could be responsible for the recovery of consciousness by ultrasound stimulation.

Interaction with Microtubules

How can ultrasound activate neurons? This remains an open question (Rezayat and Toostani, 2016). Interestingly, the mechanism originally proposed for wireless communication can also explain ultrasound stimulation. According to this mechanism, the external force, either the electromagnetic (EM) force or mechanical ultrasound pressure, may cause microtubules to dissociate from the membrane at the axon initial segment (AIS), thereby modulating neuronal excitability. In the previous chapter, only the transverse mode of microtubule vibration was considered. In fact, a microtubule can also vibrate in the longitudinal direction (Figure 2). Furthermore, a microtubule may buckle (bend) dramatically, with maximum displacement as large as 1000 nm (Figures 3 and 4), which should have significant influence on neuronal excitability (Chapter 1). The whole microtubule fascicle does not necessarily dissociate from the membrane to modulate excitability.

Images

Figure 2. A microtubule may vibrate in the longitudinal direction.

Image

Figure 3. Microtubule buckling (bending) induced by cell contraction. (A) Before contraction. (B) Under contraction, a microtubule may bend, with maximum displacement as large as 1 μm (= 1000 nm). [Source: Mehrbod and Mofrad, 2011]

Image

Figure 4. Buckling pattern of a single microtubule during contractile beating of heart cells. [Source: Mehrbod and Mofrad, 2011]

Theoretical calculations show that the transverse modes of the microtubule vibrations fall in the range 1×103 - 5×107 Hz and the longitudinal modes range from 5×106 to 3×109 Hz (Atanasov et al., 2014). Therefore, the low frequency (< 1 MHz) ultrasound may stimulate only the transverse modes (by resonance), but higher frequencies in the range 5 - 50 MHz can stimulate both transverse and longitudinal modes. Incidentally, the carrier frequency used for wireless communication in the brain is about 10 MHz.

The Role of BDNF

It has been well documented that the level of brain-derived neurotrophic factor (BDNF) decreases in Alzheimer's disease and other neurodegenerative disorders (Alzheimer's Disease). Recently, researchers have further discovered that the BDNF level in the blood correlates with the recovery from traumatic brain injury: higher BDNF has better chance to recover (Korley et al., 2016). This could be due to the important role of BDNF in neurogenesis (Vilar and Mira, 2016).

BDNF is normally stored in presynaptic vesicles. Like other neurotransmitters, they are released upon presynaptic activation. The released BDNF may trigger the BDNF-TrkB signaling pathways, resulting in the production of a variety of proteins and microRNAs, including BDNF itself. Thus, ultrasound may excite neurons to produce more BDNF, thereby facilitating the repairment of brain injuries. This has been confirmed by experiments (Tufail et al., 2010; Lin et al., 2015).

Because BDNF is associated with a wide range of neurological disorders, therapeutic potential by using ultrasound to stimulate BDNF production is tremendous. Preliminary studies are promising for Parkinson's disease, essential tremor, obsessive-compulsive disorder and epilepsy (Bauer et al., 2014; Hakimova et al., 2015). Ultrasound stimulation may also alleviate major depression and Rett syndrome which are linked to reduced BDNF level (Tsai, 2015; Tsai, 2016).

Like ultrasound, the EM waves could also excite neurons to produce more BDNF. This explains why short-term exposure to cellphone radiation can have beneficial effects such as protection against Alzheimer's disease (Mortazavi et al., 2013).

 

Author: Frank Lee
First published: November 12, 2016