|คาสิโนไทย||Global Synchronization of Alpha Rhythms||MT|
Alpha rhythms (8 - 12 Hz) are the dominant oscillations in the human brain while awake and relaxed (Klimesch, 2012; Lozano-Soldevilla, 2018). The electroencephalography (EEG) exhibits two local maxima of alpha power in the occipital lobe and anterior cingulate cortex (ACC) (Connemann et al., 2005). The posterior (occipital) alpha has been demonstrated to originate from the lateral geniculate nucleus (LGN) of the thalamus (Hughes et al., 2004; Lorincz et al., 2009). Lorazepam, a drug that reduces the occipital alpha power, did not suppress the anterior alpha (Connemann et al., 2005), suggesting that ACC and LGN are two independent sources of alpha rhythms. This notion is supported by the effects of several general anesthetics which decrease the posterior alpha while enhancing anterior alpha, a phenomenon known as "alpha anteriorization" (Vijayan et al., 2013).
Local Synchronization of the Alpha Rhythm in LGN
In LGN, a set of high-threshold thalamocortical (TC) neurons oscillate at 0.5–4 Hz when all external synaptic influences are reduced or removed (Lüthi and McCormick, 1998). The oscillating frequency of TC neurons can be modulated by the neurotransmitters, acetylcholine and glutamate, which increase the spiking rate (Lozano-Soldevilla, 2018). In relaxed wakefulness, these neurons fire at the alpha band (8 - 12 Hz) and decelerate to theta band (4-7 Hz) during early sleep (Hughes et al., 2004). The high-threshold TC neurons are interconnected by gap junctions (Lorincz et al., 2008) which are commonly used to mediate local synchronization (Chapter 6).
Local Synchronization of the Alpha Rhythm in ACC
In the neocortex, three groups of interneurons account for nearly 100% of GABAergic neurons: parvalbumin (PV)-positive fast spiking (FS) cells, somatostatin-positive low-threshold spiking (LTS) cells and 5HT3aR expressing cells (Rudy et al., 2011). As discussed in Chapter 7, the inhibitory FS cells can be used to mediate local synchronization at the gamma band. LTS cells oscillate at the alpha and beta bands (Mancilla et al., 2007). Like basket cells (a type of FS cells), they are extensively connected by gap junctions (Gibson et al., 1999; Mancilla et al., 2007). Therefore, LTS cells could be used to synchronize alpha and beta rhythms through the same mechanism as inhibitory FS cells.
During the inhibition-based synchronization, pyramidal neurons should be firing in response to continuous excitatory inputs. In ACC, the required excitatory inputs may come from TC neurons (Figure 2). The orexin neurons could also make some contribution as they project from the lateral hypothalamus to the medial prefrontal cortex, including ACC (คาสิโนไทยJin et al., 2016). A deficiency of orexin neurons has been shown to cause narcolepsy which is a chronic neurodegenerative disease characterized by excessive daytime sleepiness (De la Herrán-Arita et al., 2011). Sleep is known to associate with reduced alpha power (Bhattacharya et al., 2014).
Long-Range Synchronization Between ACC and LGN
ACC and LGN are far apart. It takes tens of milliseconds for a nerve impulse to travel from one area to another. Furthermore, alpha rhythms are synchronized between two hemispheres. Such global synchronization cannot be achieved by signal transmission through neural circuits. A plausible mechanism is the electromagnetic (EM) coupling as described in Chapter 11 and Chapter 12, which posits that the EM waves radiated from accelerating ions could influence neural activity. However, the EM power is too small to excite a neuron in the resting state. This is quite reasonable as EM waves cover the entire brain. If their power were sufficient to excite neurons from the resting membrane potential, most neurons would be excited. The typical threshold for producing spikes is roughly 15 mV, but LTS cells have a low threshold of about 12 mV (Fanselow et al., 2008), possibly to facilitate EM coupling.
ACC and LGN are connected by the reciprocal thalamocortical (TC) loop (Figure 2). As described above, the high-threshold TC neurons mediate alpha rhythms in LGN; FS cells mediate gamma rhythms while LTS cells mediate alpha and beta rhythms in ACC. Synchronization of the alpha rhythms between LGN and ACC is unlikely mediated by the TC loop alone due to significant transmission delay. However, the TC loop may change local field potential (LFP), thereby raising the membrane voltage to facilitate EM-induced neuronal spiking in ACC and LGN, as discussed below.
Suppose initially alpha rhythms are synchronized in ACC and LGN, but not between them. The activity of TC neurons in LGN may send excitatory (glutamatergic) input to LTS cells in ACC via the neural circuit. If the input is strong enough, the spiking in TC neurons should be able to induce spiking in LTS cells, but with a time delay. Therefore, in the early phase, the wire-coupled spiking in ACC and LGN are not synchronous. However, the neuronal spiking has the capacity to change LFP (Manning et al., 2009). In the auditory cortex, persistent neural activity has been shown to change LFP by as much as 5 mV (Figure 3). Similar results were observed in the prefrontal cortex (Haller et al., 2018; Supplementary Figure 4).
LFP represents the extracellular potential, i.e., Ve in Chapter 8. The membrane voltage is defined as the intracellular potential minus the extracellular potential. Therefore, in Figure 3, the decreased LFP makes the membrane voltage more depolarized, but remains below threshold. On the other hand, the EM waves radiated from synchronous TC neurons may cause microtubules to dissociate from the membrane at the axon initial segment (AIS), which also has the same effects as membrane depolarization (Chapter 3). The combined wire-coupling and EM-coupling may raise the membrane voltage above the threshold, resulting in neuronal spiking.
The change in LFP by persistent neural activity can last for more than a second. In the TC circuit, the synchronous TC neurons are likely to produce a long-lasting subthreshold LFP around LTS cells. As the LFP reaches a certain level, the spikes in TC neurons may induce spikes in LTS cells instantly via EM-coupling, since EM waves travel at the speed of light. This could be a general mechanism for long-range synchronization. According to this mechanism, the neural circuit plays a critical role in recruiting relevant brain areas into global synchronization by changing LFP in the target areas to facilitate EM-induced neuronal spiking. In other words, all areas to be engaged in global synchronization should first be "primed" to a ready state (with decreased LFP or depolarized membrane voltage) so that the EM waves may excite all of them simultaneously.
The Effects of General Anesthetics
Most general anesthetics potentiate GABAA receptors (Alkire et al., 2008). From Figure 2, we see that potentiation of GABAA receptors inhibit activity of TC neurons in LGN. This should reduce the alpha power in the posterior region. On the other hand, GABAA receptors are involved in the local synchronization of alpha rhythms in ACC. Therefore, potentiation of GABAA receptors should augment the anterior alpha power. This may explain, at least in part, the observed alpha anteriorization resulting from general anesthetics that potentiate GABAA receptors, such as propofol, halothane, isoflurane, sevoflurane, and desflurane (Xi et al., 2018).
General anesthetics induce loss of consciousness. The alpha anteriorization led to the assumption that synchronous alpha activity in the cortex may "impede responsiveness to external stimuli, thus providing a correlate for the unconscious state" (Ching et al., 2010). However, a recent study found that sevoflurane-induced unconsciousness was not correlated with alpha anteriorization, but rather with disruption of anterior-posterior phase relationships in the alpha bandwidth (Blain-Moraes et al., 2015). Another study showed that lack of responsiveness during sevoflurane anesthesia was associated with decreased alpha power (Pavone et al., 2017). In line with these findings, several anesthetics that do not cause anteriorization can still induce unconsciousness, such as ketamine and dexmedetomidine. Both of them are found to reduce alpha power (Akeju et al., 2016; Xi et al., 2018). Furthermore, during sleep, consciousness diminishes, accompanied with decrease in alpha power (Figure 4).
The Alpha Hypothesis for Consciousness
Based on the above experimental results, the following hypothesis is proposed:
Why should both anterior and posterior alpha be robust? Fundamentally, consciousness could emerge from the formation of a "คาสิโนไทย" which is a bound state of numerous gravitational waves generated by brain activities. Like electromagnetic waves, the free gravitational waves travel at the speed of light. To be bound in a small region around the brain, the gravitational waves should form standing waves. Some of gravitational waves generated in the posterior region may propagate toward the anterior region while those generated in the anterior region may propagate toward the posterior region. The gravitational waves traveling at opposite directions could form standing waves. If both anterior and posterior alpha rhythms are robust, the resulting standing waves could contain large binding energy to produce a tightly bound gravitational geon with high consciousness level. If only the anterior alpha rhythms are robust, the binding energy stored in the standing waves would be too small to produce a tight gravitational geon, consequently resulting in loss of consciousness. Further details are presented in another book, The Origin of Consciousness.
Author: Frank Lee