The article reviews the modulatory effects of noradrenaline and dopamine on prefrontal cortex (PFC) function, focusing on their roles in working memory, attention, and executive functions. It discusses how these monoamines influence cognitive processes through various techniques, including pharmacological and neuroimaging methods. The study highlights the dissociable effects of drugs and neurotoxins on monoamine systems, suggesting new ways to understand state-dependent fronto-executive functions and their implications for mental illness. The PFC is shown to regulate ascending modulatory systems, with significant influences on cognitive processes. The article also explores the role of catecholamines in cognitive flexibility and inhibitory control, emphasizing their dual roles in enhancing and impairing cognitive functions depending on the level of release. The study discusses the effects of excessive catecholamine release during stress, which can impair PFC function. It also examines the top-down control of monoamine function by the PFC and the role of monoamines in cognitive flexibility and inhibitory control. The article concludes with implications for the treatment of executive deficits in neuropsychiatric disorders such as ADHD, highlighting the potential of monoamine neuromodulators in modulating PFC dysfunction to alleviate cognitive deficits. The study also links monoamine signaling pathways to the genetics of mental illness, emphasizing the role of genes such as DISC1, RGS4, and DGKH in mental illness. The findings suggest that monoamine neuromodulators have significant effects on PFC function, contributing to cognitive fluctuations and self-control in normal subjects and more dramatically in those with mental illness. The article concludes that monoamines represent promising means of modulating PFC dysfunction to ameliorate cognitive deficits in disorders such as ADHD, bipolar disorder, and schizophrenia.The article reviews the modulatory effects of noradrenaline and dopamine on prefrontal cortex (PFC) function, focusing on their roles in working memory, attention, and executive functions. It discusses how these monoamines influence cognitive processes through various techniques, including pharmacological and neuroimaging methods. The study highlights the dissociable effects of drugs and neurotoxins on monoamine systems, suggesting new ways to understand state-dependent fronto-executive functions and their implications for mental illness. The PFC is shown to regulate ascending modulatory systems, with significant influences on cognitive processes. The article also explores the role of catecholamines in cognitive flexibility and inhibitory control, emphasizing their dual roles in enhancing and impairing cognitive functions depending on the level of release. The study discusses the effects of excessive catecholamine release during stress, which can impair PFC function. It also examines the top-down control of monoamine function by the PFC and the role of monoamines in cognitive flexibility and inhibitory control. The article concludes with implications for the treatment of executive deficits in neuropsychiatric disorders such as ADHD, highlighting the potential of monoamine neuromodulators in modulating PFC dysfunction to alleviate cognitive deficits. The study also links monoamine signaling pathways to the genetics of mental illness, emphasizing the role of genes such as DISC1, RGS4, and DGKH in mental illness. The findings suggest that monoamine neuromodulators have significant effects on PFC function, contributing to cognitive fluctuations and self-control in normal subjects and more dramatically in those with mental illness. The article concludes that monoamines represent promising means of modulating PFC dysfunction to ameliorate cognitive deficits in disorders such as ADHD, bipolar disorder, and schizophrenia.