Even through centuries passed, while neurosciences were mistaken only for phrenology, and neuronal mapping did not exist as a self-sustained science, structural changes of the brain were associated, at various degrees, with reoccurring activities or behavioural patterns of the patient. An extraordinary neuroplasticity was therefore described, meant to complete the cerebral network, which sustained superior cognitive functioning and played an essential role in adapting to the environment. Most of this web of electrical impulses has its nodes inside the frontal system, in such a way that no one lobe can be identical to another, structurally or when considering informational content. Cortical interconnectivity observed in frontal lobes may be a measure of physiological variety, but also an aid in understanding linked psychopathology. The first case we will focus our attention on is Phineas Gage, the railway worker who marked the history of neuroscience through his bizarre accident and unexpected outcome. Beyond the myth, this famous patient amended the understanding of the brain’s organization and revolutionized functional cerebral mapping. From here on, we will follow the evolution of neuronal connectivity studies and their implications in psychiatric pathology, as they are known today. Neuroimaging studies on obsessive compulsive disorders, cerebral lesions masked by different psychiatric phenomena, as well as correlations between certain affected tracts and symptoms of psychotic disturbances, are all scientific events which may offer new directions in clinical psychopathology and can invoke different therapeutic resources. In conclusion, to follow studies of neuronal mapping and use the understanding we already have, might be the answer to more complex case management, improving a patient’s outcome and helping us choose treatment plans more effectively. As a story unfolding from two opposing perspectives, the science behind cortical interconnectivity stands witness to different principles acting in conjunction for better results, should one only use it.