The default mode network (DMN) is a set of brain regions active when the mind is not engaged in specific tasks and less active during focused attention. Recent research highlights the functional role of DMN suppression in cognition and disease. The DMN is anti-correlated with task-positive networks, and its suppression is crucial for goal-directed cognition by reducing internally-focused processes like mind-wandering. Deficits in DMN suppression are linked to severe mental illnesses such as schizophrenia and depression. Studies show that lower DMN activity is associated with better cognitive performance in tasks requiring focused attention and working memory. DMN suppression is functionally relevant for cognitive control, and its disruption may contribute to cognitive impairments in schizophrenia and depression. For example, individuals with schizophrenia exhibit reduced DMN suppression during cognitive tasks, which may impair goal-directed cognition. Similarly, depression is associated with impaired DMN suppression, linked to negative rumination. Pharmacological studies suggest that modulating neurotransmission, such as with ketamine, can affect DMN suppression. Ketamine disrupts DMN deactivation and is associated with cognitive impairments similar to those seen in schizophrenia. Computational models indicate that DMN suppression involves inhibitory mechanisms and that disruptions in these mechanisms may underlie cognitive deficits in neuropsychiatric disorders. The role of DMN suppression in mental illness is complex, involving interactions with other brain networks like the fronto-parietal control network (FPCN). These networks compete for computational resources, and imbalances may contribute to cognitive dysfunction. Future research aims to understand the synaptic mechanisms underlying DMN suppression and its implications for cognitive control and mental health. The findings suggest that DMN suppression is essential for optimal cognitive function and that its disruption may be a key factor in neuropsychiatric disorders.The default mode network (DMN) is a set of brain regions active when the mind is not engaged in specific tasks and less active during focused attention. Recent research highlights the functional role of DMN suppression in cognition and disease. The DMN is anti-correlated with task-positive networks, and its suppression is crucial for goal-directed cognition by reducing internally-focused processes like mind-wandering. Deficits in DMN suppression are linked to severe mental illnesses such as schizophrenia and depression. Studies show that lower DMN activity is associated with better cognitive performance in tasks requiring focused attention and working memory. DMN suppression is functionally relevant for cognitive control, and its disruption may contribute to cognitive impairments in schizophrenia and depression. For example, individuals with schizophrenia exhibit reduced DMN suppression during cognitive tasks, which may impair goal-directed cognition. Similarly, depression is associated with impaired DMN suppression, linked to negative rumination. Pharmacological studies suggest that modulating neurotransmission, such as with ketamine, can affect DMN suppression. Ketamine disrupts DMN deactivation and is associated with cognitive impairments similar to those seen in schizophrenia. Computational models indicate that DMN suppression involves inhibitory mechanisms and that disruptions in these mechanisms may underlie cognitive deficits in neuropsychiatric disorders. The role of DMN suppression in mental illness is complex, involving interactions with other brain networks like the fronto-parietal control network (FPCN). These networks compete for computational resources, and imbalances may contribute to cognitive dysfunction. Future research aims to understand the synaptic mechanisms underlying DMN suppression and its implications for cognitive control and mental health. The findings suggest that DMN suppression is essential for optimal cognitive function and that its disruption may be a key factor in neuropsychiatric disorders.