The Basal Ganglia in Action

Abstract

The basal ganglia (BG) are the major subcortical nuclei in the brain. Disorders implicating the BG are characterized by diverse symptoms, but it remains unclear what these symptoms have in common or how they can be explained by changes in the BG circuits. This review summarizes recent findings that not only question traditional assumptions about the role of the BG in movement but also elucidate general computations performed by these circuits. To explain these findings, a new conceptual framework is introduced for understanding the role of the BG in behavior. According to this framework, the cortico-BG networks implement transition control in an extended hierarchy of closed loop negative feedback control systems. The transition control model provides a solution to the posture/movement problem, by postulating that BG outputs send descending signals to alter the reference states of downstream position control systems for orientation and body configuration. It also explains major neurological symptoms associated with BG pathology as a result of changes in system parameters such as multiplicative gain and damping.

Keywords: action selection; basal ganglia; control theory; dopamine; motor control; movement; negative feedback; striatum; substantia nigra.

Figure 1.. The place of the BG in the central nervous system.

a. The BG consist of two major groups of nuclei (striatum and pallidum). Unlike the cerebral cortex, which is characterized by glutamatergic projection neurons, the BG nuclei contain GABAergic projection neurons. The striatal regions (including caudate-putamen, nucleus accumbens) are characterized by medium spiny projection neurons which receive massive glutamatergic inputs from the entire cerebral cortex as well as intralaminar thalamus. The pallidal nuclei (including substantia nigra pars reticulata and internal globus pallidus/entopeduncular nucleus). The BG output neurons are GABAergic and usually exert an inhibitory effect on their target nuclei. It is important to emphasize that the major components of the BG as well as connectivity with the rest of the nervous system are highly conserved in evolution (Grillner and Robertson, 2015). b. The traditional event-based approach to studying behavior assumes that behavior consists of discrete events, marked by time stamps, and ignores what happens between actions or during actions. c. According to conventional action selection models, inhibitory BG output exerts tonic inhibition on downstream structures and suppresses behavior. A pause in the BG output neurons “opens the gate” and allows a specific action to be selected. The photograph is taken from www.freeimages.com.

Figure 2.. Nigrostriatal pathway and movement velocity

a. Activity of medium spiny neurons (MSN) can show strong correlation with velocity b. DA neurons show similar correlation with vector components of velocity.

Figure 3.. BG output reflect x and y coordinates of head position

The GABAergic output neurons of the SNr map instantaneous position coordinates. Top raster plots show the relationship between a SNr neuron and the y position coordinates. Below are schematic illustrations of four major classes of neurons, based on the relationship between their firing rates and position coordinates. For example, for horizontal motion, two types of neurons were found: 1) one type (red) increases firing with leftward movement and decreases firing with rightward movement; 2) a second type (blue) increases firing with rightward movement and decreases firing with leftward movement. The same is true of the vertical component of the movement along the y-axis. A change in firing rate therefore reflects a position change in a specific direction.

Figure 4.. Closed loop negative feedback control

a. The major misunderstanding is based on the assignment of the input and output of the control system, according to engineering convention, as shown in the basic diagram. In this diagram, the output is thought to be controlled, and the input is the command from the user. This way of illustrating the relationship between the controller and the environment creates the appearance that the controller is some device that transforms error into output. It ignores the autonomy of the organism, defined by intrinsic reference signals representing desired states. b. Correct illustration of the organism-environment relationship. The reference represents the “should-be” or “desired” value of a perceptual signal. Because the system produces output that, via the feedback function, reduces the discrepancy or error, it is capable of reaching the desired or referenced perception. The feedback is negative, when it reduces the error or system output. For comparison to be possible, it is necessary that the input and reference have opposite signs. Disturbances are those effects that push the value of the controlled variable away from the value specified by the reference signal, generating the error signal. As they are defined by the internal reference, they cannot be equated with physical effects in the environment. The comparator function implements a subtraction. There is no mysterious agent defying physical law. But variability in the output of a control system is to be expected, as it mirror the deviations from reference at all times. Linear causation is violated in any closed loop system, as a result of the simultaneous effects of the output on input and input on output, and the asymmetry in loop gain (usually found inside the controller). c. Illustration of a control hierarchy based on the principle of input control. On the left are the hypothesized controlled variables and their proposed neural substrates.

Figure 5.. Velocity control and position control.

a. For position controllers, a given internal reference signal specifies a position coordinate. Each degree of freedom requires a pair of controllers. For example for x axis motion, left and right. There are multiple independent controllers needed for motion in different axes (Masino, 1992). These controllers control for different orthogonal variables, e.g. horizontal and vertical motion. Orthogonal means that the effect of one does not cancel the effect of the other. Still lower levels control muscle length and muscle tension (Yin, 2014b). Their outputs would adjust the muscle length controllers and force control. For example, to maintain arm position, it is necessary to send multiple length reference signals to different length controllers. b. There are at least three independent controllers for three degrees of freedom: up-down, left-right, and forward-backward. A single value of the reference signal corresponds to a single position along an axis of motion. Thus the magnitude of the velocity error is proportional to the rate of change in the position reference. An integrator can produce steady output in the absence of any error: when the error has reached zero, the output simply stops changing. c. Due to the integrator in the output function of the velocity controller, the velocity error is turned into the rate of change in position reference.

Figure 6.. Direct and indirect pathways

a. Using the bucket analogy, the change in water level is proportional to inflow minus outflow, for any given time step. The direct pathway reflects the inflow, whereas the indirect pathway acts as the leak or damping in transition control. These two pathways exert opponent influences on the output nuclei. For example, striatonigral projections can decrease SNr firing, whereas the striatopallidal projections can increase SNr firing (Freeze et al., 2013). b. Illustration of the net effects of the two pathways on downstream structures. For the sake of simplicity, the intrinsic BG circuit connections are omitted here. Note that, because from the striatum to downstream targets there are two inhibitory synapses (striatonigral and nigrotectal), the direct pathway has a net excitatory effect on the target region of SNr outputs (e.g. tectum). Thus the bucket analogy is still useful despite the sign of the signals. Bridging collaterals from striatonigral axons to GPe, the classic indirect pathway (cortex-striatum-GPe-SNr/GPi), and the hyperdirect pathway (Cortex-STN-SNr/GPi) can all enhance damping in the transition control system. The highly plastic bridging collaterals allow adjustment of the damping constant.