The prefrontal cortex as an isomorphism machine

Wang, Xuanyu (2025): The prefrontal cortex as an isomorphism machine: structure of prefrontal activity by cognitive operations. Dissertation, LMU München: Graduate School of Systemic Neurosciences (GSN)

Abstract

Isomorphism, the principle that internal neural representations mirror the structure of external information, is a foundational property of brain computation. This organizational principle is well-established in domain-specific systems such as the sensorimotor cortices and the hippocampus. For example, in the visual cortex, the spatial relationships in the external world are preserved through retinotopic mapping, and in the hippocampus, where temporal and spatial sequences are internally reconstructed. However, whether and how this principle applies to higher-order, domain-general regions such as the prefrontal cortex remains an open question. In this thesis, I present two complementary studies in mice and non-human primates that demonstrate how the PFC adheres to the isomorphism principle across species and tasks. Both experiments involved complex behavioral paradigms requiring dynamic and flexible cognitive control. In the mouse study, I investigated how animals shift their cognitive sets (to-go or to-wait) in response to changing contexts. Neural recordings revealed that the PFC organizes itself into separable functional modules for preparatory and executive encoding. In the monkey study, I examined how animals developed different mnemonic strategies that protected task-relevant memories from competing distractions. This revealed anatomically distinct PFC subregions specialized for sensory input processing, memory storage, and retrieval. Together, these findings converge on a unifying principle: the PFC constructs an internal isomorphic “executive map” that mirrors the structure of cognitive operations in complex tasks. It functions as a modular, self-organizing system that reflects and adapts to the logic of task demands. This work suggests that isomorphism is not limited to low-level sensory systems, but extends into the architecture of executive control, offering a mechanistic framework for understanding how flexible cognition emerges from distributed, yet structured, neural dynamics.

• Item Type: Theses (Dissertation, LMU Munich)
• Subjects: 500 Natural sciences and mathematics; 500 Natural sciences and mathematics > 570 Life sciences
• Faculties: Graduate School of Systemic Neurosciences (GSN)
• Language: English
• Date of oral examination: 4. November 2025
• 1. Referee: Jacob, Simon
• Signature of the printed copy: 0001/UMC 31966