Hierarchical Encoding of Millisecond-Scale Temporal Configuration of Sound in the Mammalian Auditory Pathway

Natural sounds are defined not only by their spectral content but also by their fine temporal structure. Here we show that millisecond-scale temporal configuration—defined by the ordering of inter-click intervals (ICIs) within a click train—behaves as a distinct auditory feature, conserved across species and emerging hierarchically along the auditory pathway. Human listeners reliably discriminated click trains that shared the same average ICI but differed in temporal configuration, and these differences elicited robust mismatch negativity (MMN) responses in an oddball paradigm, indicating automatic cortical deviance detection. Awake rats showed analogous MMN-like ECoG responses to configuration changes, demonstrating cross-species generality. Neuropixels recordings along the inferior colliculus–medial geniculate body–primary auditory cortex (IC–MGB–A1) axis revealed minimal configuration sensitivity in IC, intermediate sensitivity in MGB, and strong stimulus-specific adaptation to temporal configuration in A1. Reversible cooling of auditory cortex reduced configuration sensitivity in MGB, implicating corticothalamic feedback in shaping thalamic representations. Layer-resolved analyses further showed that supragranular A1 neurons carry stronger configuration-specific adaptation than infragranular neurons. These findings identify temporal configuration as a feature-like dimension of sound and delineate a hierarchical, feedback-dependent IC–MGB–A1 circuit architecture for encoding fine temporal structure in the mammalian brain.