Amandola, Matthew; Kim, Michael E.; Rheault, Fran莽ois; Landman, Bennett; Schilling, Kurt (2026).听.听Human Brain Mapping, 47(5), e70520.听
For many years, studies in non-human primates have shown that the聽prefrontal cortex (PFC)鈥攁 part of the brain involved in decision-making, planning, and complex thinking鈥攃ontains a dense network of聽short-range connections(local wiring between nearby brain regions). However, studying these fine connections in living humans has been difficult because non-invasive imaging methods like聽diffusion tractography聽(a technique that estimates brain pathways by tracking water movement) can produce inaccurate results, including false connections.
In this study, researchers developed a new approach to map these local brain connections more reliably in living humans. They combined high-resolution tractography with prior knowledge from聽histology (microscopic studies of brain tissue, considered a gold standard for anatomical detail) to guide their analysis. Using brain scans from over 1,000 individuals, they were able to map 91 specific short-range connections within and between five key regions of the PFC. Their method showed strong agreement with known anatomical data, achieving over 80% precision (correctly identified connections) and over 70% accuracy (overall correctness compared to histological findings). Importantly, the results captured not only general patterns of connectivity but also subtle details that had previously only been observed in invasive studies.
The study also found that these brain connections are highly consistent within the same person over time, yet vary meaningfully between individuals鈥攕uggesting each person has a stable but unique 鈥渨iring pattern鈥� in their PFC. Overall, this work demonstrates that combining detailed anatomical knowledge with advanced imaging can significantly improve our ability to map the human brain鈥檚 internal connections. This opens new possibilities for understanding how local brain circuits support thinking and behavior, and how they may be altered in neurological or psychiatric conditions.
FIGURE 1
(a.) Schematic depicting the interconnections of the prefrontal cortex (PFC). Each dot represents a connection with histological precedence. Red = dl-PFC (dorsolateral prefrontal), blue = vl-PFC (ventrolateral prefrontal), orange = orbitofrontal, purple = F. Pole (frontal pole), green = ACC (anterior cingulate). (b.) Table overview of histologically supported connections. + = consistently shown in histological literature.