Optimal decoding of neural dynamics occurs at mesoscale spatial and temporal resolutions.

Introduction: Understanding the neural code has been one of the central aims of neuroscience research for decades. Spikes are commonly referred to as the units of information transfer, but multi-unit activity (MUA) recordings are routinely analyzed in aggregate forms such as binned spike counts, peri-stimulus time histograms, firing rates, or population codes. Various forms of averaging also occur in the brain, from the spatial averaging of spikes within dendritic trees to their temporal averaging through synaptic dynamics. However, how these forms of averaging are related to each other or to the spatial and temporal units of information representation within the neural code has remained poorly understood. Materials and methods: In this work we developed NeuroPixelHD, a symbolic hyperdimensional model of MUA, and used it to decode the spatial location and identity of static images shown to Results: For almost all subjects, we found 125ms temporal resolution to maximize decoding accuracy for both the spatial location of Gabor patches (81 classes for patches presented over a 9×9 grid) as well as the identity of natural images (118 classes corresponding to 118 images) across the whole brain. This optimal temporal resolution nevertheless varied greatly between different regions, followed a sensory-associate hierarchy, and was significantly modulated by the central frequency of theta-band oscillations across different regions. Spatially, the optimal resolution was at either of two mesoscale levels for almost all mice: the area level, where the spiking activity of all neurons within each brain area are combined, and the population level, where neuronal spikes within each area are combined across fast spiking (putatively inhibitory) and regular spiking (putatively excitatory) neurons, respectively. We also observed an expected interplay between optimal spatial and temporal resolutions, whereby increasing the amount of averaging across one dimension (space or time) decreases the amount of averaging that is optimal across the other dimension, and vice versa. Discussion: Our findings corroborate existing empirical practices of spatiotemporal binning and averaging in MUA data analysis, and provide a rigorous computational framework for optimizing the level of such aggregations. Our findings can also synthesize these empirical practices with existing knowledge of the various sources of biological averaging in the brain into a new theory of neural information processing in which the