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Diffusion-weighted magnetic resonance imaging (dMRI) allows non-invasive investigation of whole-brain connectivity, which can potentially help to reveal the brain's global network architecture and abnormalities involved in neurological and mental disorders. However, the reliability of connection inferences from dMRI-based fiber tracking is still debated, due to low sensitivity, dominance of false positives, and inaccurate and incomplete reconstruction of long-range connections. Furthermore, parameters of tracking algorithms are typically tuned in a heuristic way, which leaves room for manipulation of an intended result. Here we propose a data-driven framework to optimize and validate parameters of dMRI-based fiber-tracking algorithms using neural tracer data as a reference. Japan's Brain/MINDS Project provides invaluable datasets containing both dMRI and neural tracer data from the same primates. We considered four criteria for goodness of fiber tracking: distance-weighted coverage, true/false positive ratio, projection coincidence, and commissural passage, applied using a multi-objective optimization algorithm. We implemented a variant of non-dominated sorting genetic algorithm II (NSGA-II) to optimize five major parameters of a global fiber-tracking algorithm over multiple brain samples in parallel. Using optimized parameters compared to the default parameters, dMRI-based fiber tracking performance was significantly improved, while minimizing false positives and impossible cross-hemisphere connections. Parameters optimized for 10 tracer injection sites showed good generalization capability for other brain samples. These results demonstrate the importance of data-driven adjustment of fiber-tracking algorithms and support the validity of dMRI-based tractography, if appropriate adjustments are employed.

Understanding the connectivity in the brain is an important prerequisite for understanding how the brain processes information. In the Brain/MINDS project, a connectivity study on marmoset brains uses two-photon microscopy fluorescence images of axonal projections to collect the neuron connectivity from defined brain regions at the mesoscopic scale. The processing of the images requires the detection and segmentation of the axonal tracer signal. The objective is to detect as much tracer signal as possible while not misclassifying other background structures as the signal. This can be challenging because of imaging noise, a cluttered image background, distortions or varying image contrast cause problems. We are developing MarmoNet, a pipeline that processes and analyzes tracer image data of the common marmoset brain. The pipeline incorporates state-of-the-art machine learning techniques based on artificial convolutional neural networks (CNN) and image registration techniques to extract and map all relevant information in a robust manner. The pipeline processes new images in a fully automated way. This report introduces the current state of the tracer signal analysis part of the pipeline.

The state space of a conventional Hopfield network typically exhibits many different attractors of which only a small subset satisfy constraints between neurons in a globally optimal fashion. It has recently been demonstrated that combining Hebbian learning with occasional alterations of normal neural states avoids this problem by means of self-organized enlargement of the best basins of attraction. However, so far it is not clear to what extent this process of self-optimization is also operative in real brains. Here we demonstrate that it can be transferred to more biologically plausible neural networks by implementing a self-optimizing spiking neural network model. In addition, by using this spiking neural network to emulate a Hopfield network with Hebbian learning, we attempt to make a connection between rate-based and temporal coding based neural systems. Although further work is required to make this model more realistic, it already suggests that the efficacy of the self-optimizing process is independent from the simplifying assumptions of a conventional Hopfield network. We also discuss natural and cultural processes that could be responsible for occasional alteration of neural firing patterns in actual brains, Comment: 22 pages, 6 figures; Neural Networks, in press