In this work, we propose a mathematical model that describes how the mesothalamic dopamine pathway modulates the attentional focus via the thalamocortical loop, and how mesothalamic dopamine alterations can promote inattention symptoms in patients with Parkinson's disease (PD) and attention deficit hyperactivity disorder (ADHD). We model the thalamocortical loop with a neuronal network where each thalamic neuron is described by a system of coupled differential equations reflecting neurophysiological properties. The computational simulations reflect neurochemical features of PD and ADHD. Our results suggest that the mesothalamic dopamine hypoactivity causes difficulties in attentional shifting. Conversely, the mesothalamic dopamine hyperactivity hinders the attentional focus consolidation. Furthermore, regardless of the amount of mesothalamic dopamine activity, the mesocortical dopamine hypoactivity leads to loss of attentional focus. Finally, we identify a unique neuronal mechanism underlying attention deficits in PD and ADHD and relate different inattention symptoms in ADHD to different dopaminergic levels in the brain circuit modeled.
no TDAH. Objetivo: Elaboração de um modelo neurocomputacional a partir do conhecimento do funcionamento bioquímico dos sistemas dopaminérgicos mesocortical e mesotalâmico, a fim de investigar a influência dos ní-veis de dopamina na via mesotalâmica sobre o circuito tálamo-cortical e suas implicações nos sintomas de desatenção do TDAH. Método: Através de um conjunto de equações modelamos propriedades fisiológi-cas de neurônios talâmicos. A seguir, simulamos computacionalmente o comportamento do circuito tála-mo-cortical variando os níveis de dopamina nas vias mesotalâmica e mesocortical. Resultados: Em relação à via mesotalâmica, a hipoatividade dopaminérgica dificulta o deslocamento do foco de atenção, e a hiperatividade dopaminérgica acarreta desfocalização atencional. Quando tais situações são acompanhadas de hipoatividade dopaminérgica mesocortical, surge uma incapacidade em perceber estímulos, devido à competição sem vencedores entre regiões talâmicas pouco ativadas. A desatenção no TDAH também se origina em desequilíbrios dopaminérgicos na via mesotalâmica, que levam à focalização excessiva ou à desfocalização da atenção. Conclusão: O nosso experimento in silico sugere que no TDAH a desatenção relaciona-se com alterações dopaminérgicas, que não se restringem à via mesocortical. PALAVRAS-CHAVE: neurociência computacional, circuito tálamo-cortical, via dopaminérgica mesotalâmica, atenção, transtorno de défict de atenção e hiperatividade.A neurocomputational model for the thalamocortical loop: towards a better understanding of attention deficit hyperactivity disorder ABSTRACT -Background: Inattention symptoms observed in patients with attention deficit hyperactivity disorder (ADHD) are mostly related to a hipoactivity in the mesocortical dopaminergic pathway. However, mesothalamic dopaminergic variations also affect the attentional control, and possibly lead to attention alterations in ADHD. Purpose: Elaborating a neurocomputational model from biochemical knowledge of mesocortical and mesotalamic dopamine systems, to investigate how different levels of mesothalamic dopamine influence the thalamocortical loop, leading to some attention deficits observed in ADHD. Method: First, we model physiological properties of thalamic neurons with a set of mathematical equations. Next, we simulate computationally the modeled thalamocortical loop under different levels of mesothalamic dopamine, and also the mesocortical dopaminergic decrease. Results: Low levels of mesothalamic dopamine hinders the attentional shift and, high levels of such neuromodulator lead to distraction. When such alterations occur together with a decrease in the mesocortical dopamine level, the attention deficit turns into incapacity of perceiving environmental stimuli, due to a no winner competition between low activated thalamic areas. Inattention in ADHD also has its origins in dopaminergic disturbs throughout the mesothalamic pathway, which enhance a high focusing or do not allow the attention focus consolidation. Conclusion: In ADHD, the inattenti...
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