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Neurobiological hypotheses

The inability to suppress inappropriate behaviors or thoughts is the common core deficit in ADHD, TS, and OCD, which are often present as comorbid conditions. Impulsivity in ADHD, involuntary movements and vocalizations in TS, and obsessions or compulsions in OCD might reflect a common immature inhibitory control of the basal ganglia thalamo-cortical circuits, as proposed by Casey et al. (2001). Several parallel frontal-subcortical circuits have been described, which originate from different frontal cortical areas and control different sets of behaviors (Tekin and Cummings, 2002). The motor circuit originates from the premotor cortex, supplementary motor areas, and primary motor cortex, whereas the oculomotor circuit starts from the supplementary eye fields and frontal eye fields, these circuits subserve voluntary skeletal and eye movement control. The dorsolateral prefrontal circuit and the lateral orbitofrontal circuit (originating from the dorsolateral and inferior lateral PFC, respectively) are involved in executive functions, such as action planning and decision-making. While the medial orbitofrontal circuit and the anterior cingulate circuit (collectively termed as the limbic circuit, because they project to limbic structures, such as the nucleus accumbens) regulate actions influenced by emotions. The basal ganglia thalamo-cortical circuits project back to their respective areas of origin in the frontal cortex, forming closed loops (Figure 3). The anatomical definition of the basal ganglia can be strict, meaning only the striatum (i.e., the caudate nucleus and putamen together) and the globus pallidus. In the present paper, we use the functionally related basal ganglia system definition that also incorporates the substantia nigra and the subthalamic nucleus (Bentivoglio and Morelli, 2005). The basal ganglia circuits are composed of a direct (excitatory) pathway facilitating cortically mediated behaviors and an indirect (inhibitory) pathway inhibiting conflicting behaviors (Figure 3). Recently a hyperdirect pathway, which bypasses the striatum by connecting the motor cortex to the subthalamic nucleus, is also included in the model (Nambu et al., 2002). In the proposed model, the frontal cortical areas plan the actions, then through the sequential information processing of the three pathways in the basal ganglia the competing actions are inhibited and the desired motor program is selected. Afterwards, the relevant information is relayed to the primary motor cortex, from where the commands for the actual movements go to the brainstem or spinal motor neurons. A hypofunctioning direct pathway may result in interrupted behaviors (problems with sustaining attention and impulsive actions) that are characteristic of ADHD, whereas a disruption of the indirect pathway may cause irrepressible repetitive behaviors and thoughts, such as those observed in association with TS and OCD. Alternatively, a hyperactive direct pathway may lead to repetitive behaviors and thoughts, and an overactive indirect pathway may cause interrupted behaviors. The results of neuroimaging studies have illustrated the involvement of the motor, orbitofrontal, and limbic circuits in ADHD, of the motor and limbic circuits in TS, and of the dorsolateral prefrontal and limbic circuits in OCD (Sheppard et al., 1999). More recent review papers that summarize brain imaging studies have indicated a reduction in the right cerebral volume, the right caudate nucleus, and the cerebellum in ADHD (Valera et al., 2007), whereas only a reduced volume of the caudate nucleus has been convincingly shown for TS (Albin and Mink, 2006).

Figure 3

Date: 2016-01-03; view: 179

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Dopamine D5 receptor gene (DRD5) | Attention deficit hyperactivity disorder
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