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Pairwise maximum-entropy models have been used in neuroscience to predict the activity of neuronal populations, given only the time-averaged correlations of the neuron activities. This paper provides evidence that the pairwise model, applied to experimental recordings, would produce a bimodal distribution for the population-averaged activity, and for some population sizes the second mode would peak at high activities, that experimentally would be equivalent to 90% of the neuron population active within time-windows of few milliseconds. Several problems are connected with this bimodality: 1. The presence of the high-activity mode is unrealistic in view of observed neuronal activity and on neurobiological grounds. 2. Boltzmann learning becomes non-ergodic, hence the pairwise maximum-entropy distribution cannot be found: in fact, Boltzmann learning would produce an incorrect distribution; similarly, common variants of mean-field approximations also produce an incorrect distribution. 3. The Glauber dynamics associated with the model is unrealistically bistable and cannot be used to generate realistic surrogate data. This bimodality problem is first demonstrated for an experimental dataset from 159 neurons in the motor cortex of macaque monkey. Evidence is then provided that this problem affects typical neural recordings of population sizes of a couple of hundreds or more neurons. The cause of the bimodality problem is identified as the inability of standard maximum-entropy distributions with a uniform reference measure to model neuronal inhibition. To eliminate this problem a modified maximum- entropy model is presented, which reflects a basic effect of inhibition in the form of a simple but non-uniform reference measure. This model does not lead to unrealistic bimodalities, can be found with Boltzmann learning, and has an associated Glauber dynamics which incorporates a minimal asymmetric inhibition. networks, under particular assumptions. The pairwise maximum-entropy model only uses the first two moments among those observables, and can be interpreted as a network with only pairwise interactions. If correlations are on average positive, we here show that the maximum entropy distribution tends to become bimodal. In the application to neuronal activity this is a problem, because the bimodality is an artefact of the statistical model and not observed in real data. This problem could also affect other fields in biology. We here explain under which conditions bimodality arises and present a solution to the problem by introducing a collective negative feedback, corresponding to a modified maximum- entropy model. This result may point to the existence of a homeostatic mechanism active in the system that is not part of our set of observable units. [ABSTRACT FROM AUTHOR]