Modular organization of the prefrontal cortex: The legacy of patricia goldman-rakic

Abstract

The prefrontal cortex (PFC) is the brain area that distinguishes us asuniquely human. It guides decision making based on past experience, allowing us tobreak away from reflexively responding to the sensory conditions on hand at anymoment. Sequential planning, cognitive flexibility and rational thinking all rely onthe PFC. When Patricia Goldman-Rakic began her research career in the 1970s, thePFC was a terra incognita. Her work dispelled the notion that higher cognitivefunction is beyond the reach of the scientific method and revealed the basic neurobiology governing prefrontal executive function. Goldman-Rakic started her journey by probing the behavior disrupted by lesions in the PFC. An early foray into anatomic tract tracing led to the discovery of columns of afferent terminal labeling in the PFC. From this foothold, she began a relentless quest to understand the modular organization of prefrontal architecture and how the vertical arrangement of functionally related neurons translates into the mechanistic underpinnings of working memory. She characterized neuronal activity in the PFC that forms the essence of spatial mnemonic capacity. Her work teased apart the intricacies of local neurocircuitry in the PFC and examined modulation of this circuitry by monoaminergic neurotransmitters, especially dopamine. Goldman-Rakic’s studies of executive function extended from the regional level in distinguishing the dorsal and ventral domains that process spatial and object information, respectively, to the subcellular level in mapping the precise distribution of dopamine receptors. Her life’s work stands today as the foundation for our contemporary understanding of prefrontal cortical function.