Next I turn to characterization of the nature of control exerted by the frontal systems, relying here on formulations articulated by Pribram and McGuiness,10,11,43 Fuster,44 and GoldmanRakic.45

Finally, I attempt to show how the fundamental principles of frontal executive control mechanisms may operate to subserve stability and flexibility Inhibitors,research,lifescience,medical operations (which are a critical component particularly of Pribram’s concept of frontal function) via an anatomic organization that has evolved specifically to provide autoregulatory control over stability and flexibility, based on the original work of Frledrich Sanides37 as elaborated by Pandya and his colleagues.46-49 The Luria/Goldberg hierarchical and gradiental theories Among the most successful and enduring Inhibitors,research,lifescience,medical general theories of frontal lobe functioning are the hierarchical models that were developed by Luria In the 1960s and elaborated and extended by others, including Joaquin Fuster and Luria’s student Elkhonon Goldberg. A major premise of these

models is that the frontal lobes are organized in a hierarchical fashion, which Luria referred to as primary, secondary, and tertiary divisions of the frontal cortex. These primary, secondary, and tertiary divisions approximate the cytoarchitectonic divisions referring to the primary motor cortex, the premotor Inhibitors,research,lifescience,medical cortex, and the prefrontal cortex, respectively. Syndrome analysis of patients with discrete 17-AAG ic50 lesions showed systematic increases in the complexity of behavioral disruptions paralleling the cytoarchitectonic progression. In brief, discrete lesions in the Inhibitors,research,lifescience,medical primary motor cortex cause loss of motor control (paralysis or paresis), at the level of individual motor units, with relatively little impact on other non-motor functions, and the dysfunction is well defined by a somatotopic representation mapped as a motor homunculus on precentral gyrus. In contrast, lesions to the premotor regions yield hierarchically “higher-order” functional deficits, Inhibitors,research,lifescience,medical impacting the combined activation of units in the primary Olopatadine motor regions, and preferentially affecting

the spatially and temporally organized sequencing of motor movements; however, the capacity to execute elementary movements of individual motor units may be spared. While the impact of lesions in these premotor or secondary divisions continues to be predominantly motoric in character, and maintains elements of somatotopic representation, the “projective fields” are larger, involving multiple motor units. Finally, lesions to the prefrontal cortex are seen as hierarchically higher still, impacting the coordination of premotor activation and thereby regulating the organization of complex actions and plans for behavior. These prefrontal lesions may cause no obvious impact on motor control at all, and there is no clear relation to somatotopic maps.