Decoders for brain-computer interfaces (BCIs) assume constraints on neural activity, chosen to reflect scientific beliefs while yielding tractable computations. Recent scientific advances suggest that the true constraints on neural activity, especially its geometry, may be quite different from those assumed by most decoders. We designed a decoder, MINT, to embrace statistical constraints that are potentially more appropriate. If those constraints are accurate, MINT should outperform standard methods that explicitly make different assumptions. Additionally, MINT should be competitive with expressive machine learning methods that can implicitly learn constraints from data. MINT performed well across tasks, suggesting its assumptions are well-matched to the data. MINT outperformed other interpretable methods in every comparison we made. MINT outperformed expressive machine learning methods in 37 of 42 comparisons. MINT’s computations are simple, scale favorably with increasing neuron counts, and yield interpretable quantities such as data likelihoods. MINT’s performance and simplicity suggest it may be a strong candidate for many BCI applications.

Dendritic branching and synaptic organization shape single-neuron and network computations. How they emerge simultaneously during brain development as neurons become integrated into functional networks is still not mechanistically understood. Here, we propose a mechanistic model in which dendrite growth and the organization of synapses arise from the interaction of activity-independent cues from potential synaptic partners and local activity-dependent synaptic plasticity. Consistent with experiments, three phases of dendritic growth – overshoot, pruning, and stabilization – emerge naturally in the model. The model generates stellate-like dendritic morphologies that capture several morphological features of biological neurons under normal and perturbed learning rules, reflecting biological variability. Model-generated dendrites have approximately optimal wiring length consistent with experimental measurements. In addition to establishing dendritic morphologies, activity-dependent plasticity rules organize synapses into spatial clusters according to the correlated activity they experience. We demonstrate that a trade-off between activity-dependent and -independent factors influences dendritic growth and synaptic location throughout development, suggesting that early developmental variability can affect mature morphology and synaptic function. Therefore, a single mechanistic model can capture dendritic growth and account for the synaptic organization of correlated inputs during development. Our work suggests concrete mechanistic components underlying the emergence of dendritic morphologies and synaptic formation and removal in function and dysfunction, and provides experimentally testable predictions for the role of individual components.