Large cranial windows distort auditory cortical maps and degrade feature integration in secondary auditory cortex

Understanding how sensory information is transformed along cortical hierarchies requires reliable measurement of sensory representations across areas. In vivo two-photon calcium imaging through chronic cranial windows has become an essential approach for characterizing cortical sensory representations with cellular resolution and spatial registration across experiments. However, cortical computations, particularly in higher-order cortices, depend on intricate intracortical circuitry and can be sensitive to subtle tissue perturbations introduced during surgical preparation. By comparing sensory maps in the mouse auditory cortex before and after window implantation, we show that commonly used large cranial windows mechanically compress the intrinsically curved cortical surface, producing systematic map distortion away from the window center. Macroscopic and cellular-level analyses further reveal deterioration of feature-selective responses in the secondary auditory cortex following such distortion. Together, these findings identify an overlooked but controllable surgical factor that can bias measurements of sensory representations and highlight an important consideration for reproducibility across studies.