|MT > 13. Global Synchronization of Alpha Rhythms|
Alpha rhythms (8 - 12 Hz) are the dominant oscillations in the human brain while awake and relaxed (Klimesch, 2012). The electroencephalography (EEG) exhibits two local maxima of alpha power in the occipital lobe and anterior cingulate cortex (ACC) (Connemann et al., 2005). The occipital alpha has been demonstrated to originate in 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 ACC 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 Alpha Rhythms in the Thalamus
The thalamus is crucial for relaying sensory information to the cerebral cortex via thalamocortical (TC) neurons in lateral geniculate nucleus (LGN), medial geniculate nucleus (MGN) and ventrobasal complex (VB), projecting to visual, auditory and somatosensory cortices, respectively. VB consists of the ventral posteromedial nucleus (VPM) and the ventral posterolateral nucleus (VPL). In slices isolated from these relay nuclei, a subset of TC neurons, called high-threshold TC (HTC) neurons, exhibit alpha oscillations (Lorincz et al., 2009). In each sensory thalamic nucleus, HTC neurons are interconnected by gap junctions (Lorincz et al., 2008), which could mediate local synchronization (Chapter 6).
Local Synchronization of Alpha Rhythms in the Cortex
In the cortex, there are three types of GABAergic interneurons: parvalbumin (PV)-positive, somatostatin (SOM or SST)-positive and cholecystokinin (CCK)-positive. CCK cells are also called 5HT3R interneurons because they express 5-HT3 receptors. The PV cells oscillate at the gamma band (30-80 Hz) which is critical for cognition. They are also referred to as fast-spiking (FS) interneurons. SOM cells fire at 10-30 Hz with low threshold, thus also called low-threshold-spiking (LTS) interneurons (Mancilla et al., 2007). During theta oscillations, CCK cells fire at 8.8 ± 3.3 Hz on the ascending phase of theta waves (Klausberger et al., 2005). Note that SOM cells oscillate mainly in the beta band (13 - 30 Hz) while CCK cells oscillate predominantly in the alpha band.
It has been well documented that gamma oscillations of pyramidal neurons are synchronized by PV cells (Chapter 7). Similarly, the alpha oscillations of pyramidal neurons could be paced by CCK cells. In support of this idea, the HTC neurons have been found to project directly to cortical inhibitory interneurons that target pyramidal neurons (Vijayan and Kopell, 2012, Figure 5). The inhibitory interneurons could be CCK cells as CCK binding sites consistently coincide with the cortical projections of thalamic nuclei: CCK binding in the primary visual cortex corresponds to the terminal field disposition of LGN while in somatosensory cortex, the pattern of CCK binding in layer IV coincides with thalamic inputs arising from the ventrobasal complex (Kritzer et al., 1987).
CCK cells exist not only in the sensory cortex. In fact, they are most numerous within the medial prefrontal cortex (which includes ACC) (Whissell et al., 2015). The neuropeptide CCK is especially abundant in the ACC (Ere et al., 2004; Gustafsson et al., 2000). Like PV interneurons, CCK cells are connected by gap junctions (Ma et al., 2011). Therefore, CCK cells may be employed to synchronize the alpha rhythms of pyramidal neurons in both prefrontal and sensory cortices through the same mechanism as PV cell-synchronized gamma rhythms of pyramidal neurons (Chapter 7). During the inhibition-based synchronization, pyramidal neurons should be firing in response to continuous excitatory inputs. In the cortex, the required excitatory inputs may come from regular TC neurons and other inputs (Figure 3).
Thalamocortical Long-Range Synchronization in the Alpha Band
The alpha oscillations in the neocortex and LGN are in phase with zero lag (Vijayan and Kopell, 2012). Such zero phase lag synchronization between remote areas cannot be achieved by signal transmission through neural circuits alone due to significant transmission delay. The electromagnetic (EM) coupling as described in Chapter 11 and Chapter 12 could also be involved. Importantly, the EM waves cover the entire brain. Their power should not be sufficient to excite neurons from the resting membrane voltage, for otherwise most neurons would be excited. Generally, all regions to be engaged in large-scale synchronization should first be depolarized to a certain subthreshold level such that the EM waves may excite all of them simultaneously. The subthreshold depolarization may arise from alteration in the local field potential (LFP) at the relevant region.
Suppose initially alpha rhythms are locally synchronized in LGN. The neural activity of LGN may send excitatory input to CCK cells in the cortex via the HTC neurons. If the input is strong enough, the spikes of HTC neurons should be able to induce spikes in CCK cells, but with a time delay. Therefore, in the early stage, the wire-coupled spikes in the cortex and LGN are not synchronous. However, the neuronal spiking has the capacity to change LFP (Manning et al., 2009), thereby raising the membrane voltage to facilitate EM-induced neuronal spiking. In the auditory cortex, persistent neural activity has been shown to change LFP by as much as 5 mV (Figure 4). 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 4, the decreased LFP makes the membrane voltage more depolarized, but remains below threshold. On the other hand, the EM waves radiated from synchronous HTC 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 of CCK cells above the threshold, resulting in neuronal spikes.
The change of LFP by local neural spiking does not go away immediately after the spikes terminate. It could last for a few seconds if neurons are connected by gap junctions. This type of memory traces may be called the "working memory". The duration of the working memory should be long enough to recruit all relevant brain regions into large-scale synchronization through changes in LFP. The recruitment is carried out by "wire coupling", namely, signal transmission along neural circuits. It takes about 30 milliseconds (ms) for a nerve impulse to travel from one hemisphere to the other through myelinated axons in the corpus callosum, and 150 - 300 ms through unmyelinated axons (Fields, 2008). Therefore, to recruit all relevant regions in the entire brain may take a few seconds.
Global Synchronization of Alpha Rhythms
During deep sleep, consciousness is lost. The recovery of consciousness is induced by the ascending arousal system involving cholinergic neurons in pediculopontine tegmental (PPT) and laterodorsal tegmental (LDT). These cholinergic neurons are known to innervate all sensory thalamic nuclei (Steriade et al., 1988) and anterior thalamic nuclei (ATN) (Holmstrand and Sesack, 2011). ATN has reciprocal connections with ACC through TC neurons (Jankowski et al., 2013). Therefore, the cholinergic neurons from PPT/LDT may activate sensory thalamic nuclei as well as ATN to recruit CCK cells in both sensory cortex and ACC into global alpha synchronization. More specifically, the TC neurons may trigger neural spikes in both sensory cortex and ACC. The local neural spikes can then alter LFP, making the membrane voltage of CCK cells more depolarized for a few seconds even after the termination of neural spikes. This should facilitate excitation by the EM waves radiated from already synchronized neurons (including CCK cells and targeted pyramidal neurons). In this manner, all CCK cells in both anterior and posterior cortices can be synchronized by the EM coupling, as long as they have been depolarized to a certain subthreshold level.
Author: Frank Lee