Geon 14. Global Synchronization of Beta Rhythms MT

 

Beta oscillations (13 - 30 Hz) are known to associate with sensorimotor processing (Spitzer and Haegens, 2017). Their abnormalities can lead to motor deficits as observed in Parkinson's disease (PD) (Weinberger et al., 2006; Tinkhause et al., 2018) and amyotrophic lateral sclerosis (ALS) (Proudfoot et al., 2017; Proudfoot et al., 2018). An example of long-range synchronization at the beta band is shown in Figure 1, where the subthalamic nuclei (STN) in both hemispheres oscillate at predominantly zero phase lag.

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Figure 1. Histogram of beta phase differences between subthalamic nuclei in both hemispheres for 23 human subjects with Parkinson's disease. Note the predominance of zero phase lag. [Source: Little et al., 2013]

The Beta-Oscillating Network

The beta-oscillating network may be divided into four pathways: direct, indirect, thalamocortical and hyperdirect (Figure 2). The direct and indirect pathways are responsible for action selection: Go or NoGo. The direct pathway from the striatum to the thalamus involves two inhibitions by the GABAergic neurons: striatum on GPi/SNr and GPi/SNr on the thalamus. The indirect pathway involves three inhibitions: striatum on GPe, GPe on STN, and GPi/SNr on the thalamus. As a result, the direct pathway leads to the activation of the thalamus, which in turn triggers movement via corticospinal motor neurons (Figure 3). The indirect pathway inhibits thalamic activation and motor activity.

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Figure 2. The beta-oscillating network, including direct, indirect, thalamocortical and hyperdirect pathways. Parkinson's disease is caused by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNc), which in turn may arise from exaggerated beta activity, particularly the excessive long-range coupling between the motor cortex and subthalamic nucleus (STN).

Thalamocortical Pathway

A model for the thalamocortical pathway involved in beta oscillations is depicted in Figure 3 based on the following information:

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Figure 3. The proposed microcircuit for the thalamocortical circuit involved in beta oscillations. Thalamocortical (TC) neurons project to pyramidal neurons and SOM-positive interneurons (SOM) in the layer 2/3 (L2/3). The L2/3 pyramidal neurons have synaptic contacts with either corticospinal or corticostriatal neurons in the layer 5.

In the L5 of motor cortex, there are two classes of pyramidal neurons: corticospinal motor neurons (including the giant Betz cells) and corticostriatal neurons. The corticospinal neurons project to the spinal cord whereas the corticostriatal neurons project to the striatum (Haber, 2016). Abnormalities in the corticospinal motor neurons cause amyotrophic lateral sclerosis (Chapter 17). Abnormalities in the corticostriatal neurons may contribute to Parkinson's disease.

Hyperdirect Pathway

The hyperdirect pathway is a direct connection between motor-related cortical areas and STN (Nambu et al., 2002). In PD, the long-range coupling between STN and motor cortex is significantly enhanced (Tinkhause et al., 2018). Recently, evidence was rapidly accumulating that low beta (13 - 20 Hz) and high beta (20 - 30 Hz) are functionally distinct (Weiss and Mueller, 2012; Little et al., 2013; van Wijk et al., 2016). Low beta has been found to associate with motor act, whereas high beta represents the motor state (AuYong et al., 2018). Since the motor act is lateralized (moving only one side of the body), the low beta should not be globally synchronized. Therefore, the high beta may be mediated by long-range coupling as discussed in previous chapters while low beta should be limited to local synchronization as described in Chapter 7.

Consistent with this notion, beta rhythms seem to have two different generators. SOM cells (also called LTS interneurons) fire at 10-30 Hz (Mancilla et al., 2007), which cover the entire beta band. A set of pyramidal neurons in layer 5 (L5) of somatosensory and motor cortices generate only high beta (20 - 30 Hz) (Roopun et al., 2006; Yamawaki et al., 2008). SOM cells may exist in STN, responsible for local synchronization of the projection neurons in STN. L5 pyramidal neurons are likely connected to the projection neurons of STN, constituting the hyperdirect pathway. Therefore, STN projection neurons can be influenced by both local synchronization mediated by SOM cells and long-range coupling involving the L5 pyramidal neurons that generate high beta (illustrated in the next chapter).

In PD, the long-range coupling between STN and the cortex is exaggerated. As predicted by the above mechanism, "the coupling within the beta range seemed to be greatest around 25 Hz and less pronounced, although still present, around 15 Hz" (Tinkhause et al., 2018). Interestingly, mutations of the PD-associated gene, PARK2, also lead to exaggerated beta synchrony, particularly in the high beta (20 - 30 Hz) (Moll et al., 2015). Its underlying mechanism is discussed in the next chapter.

 

Author: Frank Lee
First published: May 6, 2019
Last updated: August 26, 2019