ReviewDifferentiating Frontostriatal and Fronto-Cerebellar Circuits in Attention-Deficit/Hyperactivity Disorder
Section snippets
Neuroanatomical Substrate for Links Among Prefrontal Cortex, Striatum, and Cerebellum
In 1986, Alexander et al. (3) published a seminal article where they proposed that there were at least five parallel loops between the striatum and cortex. Each loop includes discrete areas in the striatum, globus pallidus, substantia nigra, thalamus, and cortex and is structured in a parallel manner: Cortical inputs to the striatum are passed through the basal ganglia to the thalamus and from there back to a single cortical area. Each circuit receives multiple inputs only from cortical areas
Linking Neuroanatomy to Brain Function
The prefrontal cortex is critical to cognitive control, the ability to flexibly adjust behavior to changing circumstances (5). Cognitive control has also been called “behavioral control” or simply “control.” Functions typically covered by this umbrella term include response inhibition, motor inhibition, switching, and sometimes planning. Tasks used to assess cognitive control include the go/no-go task, stop task, Stroop task, Wisconsin Card Sorting Test, and many others. To give but one
Cognitive Control and Dorsal Frontostriatal Connections
The frontostriatal circuit, which comprises reciprocal connections among the striatum, thalamus, and prefrontal areas, is critical to cognitive control. Deficits in this ability have even been suggested to be the core deficit in ADHD, underlying other cognitive differences (24). However, meta-analyses have shown that most children with ADHD do not have a measurable deficit in cognitive control, suggesting that it is not central to ADHD symptoms, at least not for all children (25).
According to
Fronto-Cerebellar Circuits in ADHD
Traditionally, much attention has been paid to the role of the prefrontal cortex and its links with the striatum in ADHD research. However, the cerebellum is another prime candidate for involvement in this disorder. It has a protracted development, is sexually dimorphic, and is susceptible to environmental influences (40). This tentatively provides support for a possible role in ADHD, because this disorder is usually diagnosed in middle childhood, when the cerebellum is still developing; is
Genetic Influences on Frontostriatal and Fronto-Cerebellar Circuits in ADHD
Attention-deficit/hyperactivity disorder is a disorder with a genetic component: 70%–80% of the phenotypic variance is estimated to be heritable (68). Differences in frontostriatal circuits in ADHD have indeed been shown to be under genetic influences: the unaffected siblings of boys with ADHD share reductions in prefrontal gray matter volume (48) and prefrontal activity during cognitive control (69). Furthermore, established risk genes for ADHD (DRD4 and DAT1) are related to both structure and
Dissociating Circuits with Prefrontal Cortex in ADHD
As discussed previously, dorsal frontostriatal, orbitofronto-striatal, and fronto-cerebellar circuits are involved in ADHD. These circuits interact through spiraling loops in the striatum and connections from the cerebellum to the prefrontal cortex and the striatum, although there are more connections within than between circuits. Dysfunction in any of these circuits might cause symptoms of ADHD: Dysfunction of the prefrontal cortex is likely to result in a reduced ability to exert control (5).
Where Next in ADHD Research?
The work described in the preceding text shows that we, as a field, are preparing to take the next step in ADHD research. To date, studies in ADHD have typically grouped children on the basis of symptoms and behavioral assessments. For example, in imaging genetics studies, the effect of candidate genes on the brain has been investigated in large samples of individuals with ADHD, categorized by their clinical diagnosis. As such, we have effectively ignored the fact that there might be multiple
Conclusions
In conclusion, there are multiple circuits with the prefrontal cortex that play a role in the pathophysiology of ADHD. Dorsal frontostriatal pathways are implicated in deficits in cognitive control, orbitofronto-striatal circuits relate to differences in reward processing, and fronto-cerebellar pathways are linked to problems with timing and building temporal predictions. Recent work suggests that it might be possible to dissociate these circuits at the cognitive level and use them for
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