Modulating frontostriatal regulations of attentional control and selective perception: enhancing dopamine signaling and frontal cortical excitability in attentional deficit hyperactivity disorder and aging

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Dynamic interactions between brain substrates in the frontostriatal circuit that are, in part, modulated by the dopaminergic system, play key roles in cognitive flexibility and top-down attentional regulation. Knowledge about mechanisms through which substrates of the frontostriatal circuit interact to implicate cognitive flexibility has been accumulating. For instance, dopamine may modulate this circuit by acting directly in the frontal cortex and the striatum or through influences from the prefrontal cortex on the striatum. Non-invasive brain stimulations, such as transcraninal direct current stimulation (tDCS) applied over the frontal cortex, have been shown to increase cortical excitability and improve cognition. Instead of focusing on frontostriatal mechanisms for switching between task-/rule-sets or monitoring of action outcomes/rewards as most current research on cognitive flexibility pursues, this project will investigate the less explored role of this circuitry as the regulatory interface of perceptual filtering and selective attention. Specifically, we propose that interactions between top-down attentional control and bottom-up perceptual filtering are regulated by interactive gain control mechanisms of the frontostriatal circuitry. The abilities to flexibly regulate attention are critically impaired in individuals with attention deficit hyperactivity disorder (ADHD) and are also constrained in a variety of normal states, such as brain immaturity or aging. Therefore, the proposed project will use ADHD and aging as two model conditions, which share certain functional deficits in the frontostriatal circuitry but exhibit differences in auditory processing to shed new lights on the relevance of frontostriatal circuitry in regulating interactions between selective perception and selective attention as well as advance understandings about problems of auditory perception in these conditions.Given that dopamine and membrane potential regulated neuronal gain control mechanisms have been proposed in neurocomputational models, we will therefore either enhance (i) frontostriatal dopamine pharmacologically by methylphenidate or (ii) cortical excitability via anodal tDCS stimulation. Potential interactive effects of these two approaches in regulating neuronal gain control will also be investigated in a sample of healthy young adults. Pathology- and lifespan age-related differences in behavioral and brain plasticity to pharmacological or tDCS modulations will be investigated, respectively, by contrasting ADHD and healthy individuals and by comparing healthy adolescents, young and older adults. Expected outcomes of this project will yield new insights into interactive gain control mechanisms of the frontostriatal circuitry that underlie flexible interplays between top-down attention control and bottom-up selective perception. Furthermore, the results will be of direct relevance for treating ADHD and for buffering cognitive declines in old age.