Distinct Lateral Prefrontal Regions Are Organized in an Anterior-Posterior Functional Gradient.

The dorsolateral prefrontal cortex (dlPFC) is composed of multiple anatomically defined regions involved in higher-order cognitive processes, including working memory and selective attention. It is organized in an anterior-posterior global gradient where posterior regions track changes in the environment, whereas anterior regions support abstract neural representations. However, it remains unknown if such a global gradient results from a smooth gradient that spans regions or an emergent property arising from functionally distinct regions, that is, an areal gradient. Here, we recorded single neurons in the dlPFC of nonhuman primates trained to perform a memory-guided saccade task with an interfering distractor and analyzed their physiological properties along the anterior-posterior axis. We found that these physiological properties were best described by an areal gradient. Further, population analyses revealed that there is a distributed representation of spatial information across the dlPFC. Our results validate the functional boundaries between anatomically defined dlPFC regions and highlight the distributed nature of computations underlying working memory across the dlPFC.SIGNIFICANCE STATEMENT Activity of frontal lobe regions is known to possess an anterior-posterior functional gradient. However, it is not known whether this gradient is the result of individual brain regions organized in a gradient (like a staircase), or a smooth gradient that spans regions (like a slide). Analysis of physiological properties of individual neurons in the primate frontal regions suggest that individual regions are organized as a gradient, rather than a smooth gradient. At the population level, working memory was more prominent in posterior regions, although it was also present in anterior regions. This is consistent with the functional segregation of brain regions that is also observed in other systems (i.e., the visual system).

Distinct Genetic Signatures of Cortical and Subcortical Regions Associated with Human Memory.

Despite the discovery of gene variants linked to memory performance, understanding the genetic basis of adult human memory remains a challenge. Here, we devised an unsupervised framework that relies on spatial correlations between human transcriptome data and functional neuroimaging maps to uncover the genetic signatures of memory in functionally-defined cortical and subcortical memory regions. Results were validated with animal literature and showed that our framework is highly effective in identifying memory-related processes and genes compared to a control cognitive function. Genes preferentially expressed in cortical memory regions are linked to memory-related processes such as immune and epigenetic regulation. Genes expressed in subcortical memory regions are associated with neurogenesis and glial cell differentiation. Genes expressed in both cortical and subcortical memory areas are involved in the regulation of transcription, synaptic plasticity, and glutamate receptor signaling. Furthermore, distinct memory-associated genes such as PRKCD and CDK5 are linked to cortical and subcortical regions, respectively. Thus, cortical and subcortical memory regions exhibit distinct genetic signatures that potentially reflect functional differences in health and disease, and nominates gene candidates for future experimental investigations.