@article {SloasENEURO.0124-16.2016, author = {David C. Sloas and Ran Zhuo and Hongbo Xue and Anna R. Chambers and Eric Kolaczyk and Daniel B. Polley and Kamal Sen}, title = {Interactions across Multiple Stimulus Dimensions in Primary Auditory Cortex}, elocation-id = {ENEURO.0124-16.2016}, year = {2016}, doi = {10.1523/ENEURO.0124-16.2016}, publisher = {Society for Neuroscience}, abstract = {Although sensory cortex is thought to be important for the perception of complex objects, its specific role in representing complex stimuli remains unknown. Complex objects are rich in information along multiple stimulus dimensions. The position of cortex in the sensory hierarchy suggests that cortical neurons may integrate across these dimensions to form a more gestalt representation of auditory objects. Yet, studies of cortical neurons typically explore single or few dimensions due to the difficulty of determining optimal stimuli in a high dimensional stimulus space. Evolutionary algorithms (EA{\textquoteright}s) provide a potentially powerful approach for exploring multidimensional stimulus spaces based on real time spike feedback, but two important issues arise in their application. First, it is unclear whether it is necessary to characterize cortical responses to multidimensional stimuli or if it suffices to characterize cortical responses to a single dimension at a time. Second, quantitative methods for analyzing complex multidimensional data from an EA are lacking. Here, we apply a statistical method for nonlinear regression, the Generalized Additive Model (GAM), to address these issues. The GAM quantitatively describes the dependence between neural response and all stimulus dimensions. We find that auditory cortical neurons in mice are sensitive to interactions across dimensions. These interactions are diverse across the population, indicating significant integration across stimulus dimensions in auditory cortex. This result strongly motivates using multidimensional stimuli in auditory cortex. Together, the EA and the GAM provide a novel quantitative paradigm for investigating neural coding of complex multidimensional stimuli in auditory and other sensory cortices.Significance Statement: The auditory cortex is thought to be integral for the perception of complex sounds, which are characterized by multiple stimulus dimensions such as center frequency, intensity, and bandwidth. Traditional studies of cortical neurons only consider one or few dimensions of sound at a time, but it is possible that cortical neurons integrate across these dimensions when processing sounds. Here, we apply an Evolutionary Algorithm and a Generalized Additive Model to quantitatively explore cortical response to 5-dimensional auditory stimuli. Our results demonstrate that cortical neurons are significantly driven by interactions across stimulus dimensions in ways that are not captured by low-dimensional characterizations and motivate the use of multidimensional stimuli in the study of sensory cortices.}, URL = {https://www.eneuro.org/content/early/2016/08/11/ENEURO.0124-16.2016}, eprint = {https://www.eneuro.org/content/early/2016/08/11/ENEURO.0124-16.2016.full.pdf}, journal = {eNeuro} }