dISTRIBUCIóN de LAS CoMUNIdAdeS de CRUSTÁCeoS

Beginning in the cortex, there are at least four basic circuits that traverse the basal ganglia before returning to the cortex. These circuits are a motor loop, a prefrontal (cortical) loop, a limbic loop, and an oculomotor loop (Alexander & Crutcher, 1990; Fitzgerald et al., 2007; Gale, Amirnovin, Williams, Flaherty, & Eskandar, 2008).

These four basal ganglia-thalamocortical circuits all share certain features, for example, in each circuit, specific cortical areas send excitatory (or glutaminergic) projections on to the striatum (Alexander & Crutcher, 1990). Due to their high rates of spontaneous discharge, the GPi, SNpc and ventral pallidum exert a GABA-ergic inhibitory effect on their target nuclei in the thalamus. Within each of the four previously mentioned circuits, this inhibition appears to be differentially modulated by two opposing but parallel pathways, the ‘direct’ and ‘indirect’ pathways (Alexander & Crutcher, 1990). These efferent pathways have opposing effects on the basal ganglia output nuclei and, consequently, on the thalamic targets of these nuclei. Activation of the direct pathway disinhibits the thalamus and increases thalamocortical activity, while activation of the indirect pathway further inhibits the thalamocortical neurons. In summary, activation of the direct pathway will facilitate movement, while activation of the indirect pathway will inhibit it (DeLong, 2000).

Figure 2.1. Circuit diagram for the direct and indirect pathways in the basal ganglia (Leisman et al., 2013). Neurotransmitters: Glu, glutamate; Ach,

acetylcholine; DA, dopamine; Enk, enkephalin; SP, substance P. Nuclei: GPe, external segement of the globus pallidus; GPi, internal segment of the globus

pallidus; SNc, substantia nigra pars compacta; SNr, substantia nigra pars reticulate; STN, subthalamic nucleus; VL, ventral lateral nucleus; VA, ventral

anterior nucleus.

Due to the parallel structure of these four circuits, the basal ganglia are capable of concurrent participation in a number of different functions, including cognitive, oculomotor, skeletomotor, and limbic (emotion processing & memory

formation) tasks (Alexander & Crutcher, 1990). The development of PD affects all four of these identified circuits in various ways.

2.2.1 The Motor Loop

The motor loop, primarily responsible for learned movements, and also involved in preparation for future movement (Alexander & Crutcher, 1990), begins in the sensorimotor cortex and is made up of two known pathways, the direct and the

indirect (Fitzgerald et al., 2007; Pollack, 2001). These two opposing pathways connect the striatum to the SNpr and the GPi, the output nuclei of the basal ganglia. The direct pathway travels through the corpus striatum and the thalamus and is made up of striatal projection neurons which send an inhibitory GABA projection to the output nuclei (Fitzgerald et al., 2007; Pollack, 2001). The indirect pathway differs from the direct pathway in that it consists of a separate population of striatopallidal neurons which send inhibitory GABAergic projections to the external segment of the globus pallidus (GPe). These external pallidal neurons then send a GABAergic projection to the STN, which sends an excitatory glutaminergic projection to the output nuclei (SNr & GPi) (Pollack, 2001).

Projections from the cerebral cortex and from the thalamus to the supplementary motor area arise from pyramidal cells and are glutaminergic (excitatory); projections from the striatum, GPe, and GPi arise from medium spiny neurons and are GABAergic (inhibitory; Fitzgerald et al., 2007).

2.2.2 The Limbic Loop

Primarily concerned with the emotional aspects of movement, the limbic loop passes from the inferior prefrontal cortex through the anterior aspect of the striatum

(the nucleus accumbens) and the ventral pallidum before returning to the inferior prefrontal cortex via the mediodorsal nucleus of the thalamus (Fitzgerald et al., 2007). Believed to be responsible for emotional movements such as smiling and gesturing, this route is rich in dopaminergic nerve endings; the reduction in DA levels in People with PD may explain symptoms such as mask-like facial features and a lack of spontaneous gesturing (Fitzgerald et al., 2007). In addition to this, the increased presence of Lewy bodies and Lewy neurites (discussed later in this chapter) in the thalamic components of the limbic loop nuclei may contribute to a wide range of cognitive, emotional, autonomic, somatomotor, and oculomotor dysfunctions seen in PD (Rϋb et al., 2002).

2.2.3 The Prefrontal (Cognitive) Loop

Primarily concerned with motor learning and intentions, the cortical connections of the caudate suggest that the prefrontal loop participates in planning complex motor movements (Fitzgerald et al., 2007), executive functioning, working memory, and spatial memory (Kopell & Greenburg, 2008). People with PD that have lesions in the dorsolateral prefrontal cortex exhibit difficulties with flexible thinking, hypothesis generation, maintaining and shifting of cognitive sets, and memory recall (Katzen, 2000). It is also believed that this prefrontal loop is involved in additional aspects of cognitive dysfunction such as reduced verbal fluency, poor organisational skills, reduced insight into symptom presence and severity, the ability to suppress negative emotions, and the experience of pain (Kopell & Greenburg, 2008).

Van Koningsbruggen, Pender, Machado, and Rafal (2009), investigated the role of the basal ganglia in integrating voluntary and reflexive behaviour and found that participants with PD showed impairments in exerting control over oculomotor

reflexes. As saccadic eye movements are easily measured and well understood (Chan, Armstrong, Pari, Riopelle, & Munoz, 2005), they provide a useful method for investigating and quantifying response suppression deficits in PD. Amador, Hood, Schiess, Izor, and Sereno (2006), found that, when compared to control participants, people with PD were slower to initiate saccades on all experimental tasks and had more difficultly inhibiting automatic responses. This finding has been consistent across a number of studies involving a variety of motor, cognitive and oculomotor tasks (van Koningsbruggen et al., 2009), thus indicating a general deficit in response suppression in people with PD (Chan et al., 2005).

2.2.4 The Oculomotor Loop

The oculomotor loop commences in the frontal eye field and posterior parietal cortex, passing through the caudate nucleus and the SNpr (Kimmig, Haubmann, Mergner, & Lucking, 2002). It returns via the ventral anterior nucleus of the thalamus. In addition to this, the SNpr sends an inhibitory GABAergic projection to the superior colliculus where it synapses onto cells controlling automatic saccades. The oculomotor loop is activated when a deliberate saccade is about to be made toward an object. The SNpr acts as a gate for the preparation of saccades by disinhibiting the superior colliculus (Kimmig et al., 2002). For people with PD, neuronal degradation within the SNpr leads to faulty disinhibition of the superior colliculus. As a consequence, saccade initiation tends to be slowed (oculomotor akinesia) and often inadequate, falling short of the intended target (oculomotor hypokinesia) and necessitating additional corrective saccades be made (DeJong & Jones, 1971). Oculomotor bradykinesia, or increased time lapse between visual targets, is the end result (DeJong & Jones, 1971).

2.2.5 Summary

This set of basal ganglia-thalamocortical circuits appears to have a unified role in modulating the operations of the entire frontal lobe (Alexander & Crutcher, 1990). With shared mechanisms and operating in parallel, these circuits influence processes that range from the maintenance and switching of various behavioural sets, via the prefrontal and limbic circuits, and the planning and execution of limb and eye movements, via the motor and oculomotor circuits. While it has been quite well established that these loops originate in different areas of the cortex and project to the basal ganglia, thalamus and frontal cortex in a segregated, organised, and topographic manner, the mixed presentation of symptoms in PD would suggest that there is at least some communication between the circuits (Katzen, 2000).