Chih-Chun Chen

How neurons migrate: a dynamic in-silico model of neuronal migration in the developing cortex

BackgroundNeuronal migration, the process by which neurons migrate from their place of origin to their final position in the brain, is a central process for normal brain development and function. Advances in experimental techniques have revealed much about many of the molecular components involved in this process. Notwithstanding these advances, how the molecular machinery works together to govern the migration process has yet to be fully understood. Here we present a computational model of neuronal migration, in which four key molecular entities, Lis1, DCX, Reelin and GABA, form a molecular program that mediates the migration process.ResultsThe model simulated the dynamic migration process, consistent with in-vivo observations of morphological, cellular and population-level phenomena. Specifically, the model reproduced migration phases, cellular dynamics and population distributions that concur with experimental observations in normal neuronal development. We tested the model under reduced activity of Lis1 and DCX and found an aberrant development similar to observations in Lis1 and DCX silencing expression experiments. Analysis of the model gave rise to unforeseen insights that could guide future experimental study. Specifically: (1) the model revealed the possibility that under conditions of Lis1 reduced expression, neurons experience an oscillatory neuron-glial association prior to the multipolar stage; and (2) we hypothesized that observed morphology variations in rats and mice may be explained by a single difference in the way that Lis1 and DCX stimulate bipolar motility. From this we make the following predictions: (1) under reduced Lis1 and enhanced DCX expression, we predict a reduced bipolar migration in rats, and (2) under enhanced DCX expression in mice we predict a normal or a higher bipolar migration.ConclusionsWe present here a system-wide computational model of neuronal migration that integrates theory and data within a precise, testable framework. Our model accounts for a range of observable behaviors and affords a computational framework to study aspects of neuronal migration as a complex process that is driven by a relatively simple molecular program. Analysis of the model generated new hypotheses and yet unobserved phenomena that may guide future experimental studies. This paper thus reports a first step toward a comprehensive in-silico model of neuronal migration.

Inspiration and Fixation: The Influences of Example Designs and System Properties in Idea Generation

When tackling problems, designers might be inspired by different sources, whether concrete or abstract. The more concrete sources often comprise representations of potential solutions or examples of existing designs. The more abstract sources often represent the desirable properties of engineered systems, such as modular system architectures. We performed an experiment with 60 novice designers to compare the inspiration effects from these two types of stimuli. Participants were asked to solve a design problem, having been exposed to a concrete example design, an abstract system property, both, or no stimulus at all. Their design work was assessed according to four metrics: fluency, diversity, commonness, and conformity. Exposure to either the example design or the system property reduced the fluency and diversity of ideas, and exposure to both stimuli reduced these measures even further. While there was no difference in the inspiration effects from the example and the property in terms of fluency, diversity, and commonness; results for conformity showed that each stimulus constrained participants differently: encouraging ideas similar to one type of stimulus, while discouraging ideas similar to the other type. In combination with other work on inspiration and fixation, these findings can help shape how design is taught and how inspiration tools are developed.

To Copy or Not to Copy: The Influence of Instructions in Design Fixation Experiments

Design fixation experiments often require participants to solve a design problem whilst being exposed to an example solution and instructions for how to treat that example. However, little is known about the influence of such instructions, leading to difficulties in interpreting results and understanding how the introduction of examples affects idea generation. In our experiment, participants were all provided with the same design problem and example solution, but were presented with different instructions, ranging from strongly encouraging copying the example to strongly discouraging copying. Analyses of participants’ work indicated that only the instructions encouraging copying had an effect. When encouraged to copy, participants tended to only copy the structural features of the example rather than the underlying concept. By contrast, the number of features copied was not reduced when participants were discouraged from copying. These findings suggest that there are subtle interactions between instructions and stimuli that influence design fixation.

What’s the benefit of problem exploration?

Models of the design process often start with activities of problem exploration before generating ideas, but the benefits of exploration have not been properly investigated. We did an experiment with undergraduate industrial designers during a design course. Except for the exploration methods, all teams had to follow the same design process. We observed that exploration methods increased the design teams’ perceived knowledge about the problem, but no impact on the quality of their final designs was seen. This challenges a widely held assumption about the value of problem exploration in design.

Research data supporting "To copy or not to copy: the influence of instructions in design fixation experiments"

This is a ZIP archive file (.zip) containing both portable document format (.pdf) and comma-separated values (.csv) files: > The pdf file contains the annotated sketches that participants generated during an ideation session. This file type allows the non-digital data to be saved in a digital document format. The ideas from each group are stored into different files, whose naming corresponds to the experimental conditions reported in the publication (To copy or not to copy: the influence of instructions in design inspiration and fixation experiments). > The csv file contains the evaluation for all ideas generated by all participants in the experiment. This file type allows data to be saved in a table structured format. In the table, the column headings are self-explanatory, provided you also have the corresponding publication (To copy or not to copy: the influence of instructions in design inspiration and fixation experiments) as a reference. The data was collected in January 2015 from 168 undergraduate students in engineering at the University of Cambridge, UK. Participation in the experiment was part of the students’ education, and was aimed at collecting data that could later be used to introduce them to the concept of design fixation. No demographic data was collected from the participants, but as first year undergraduate students they were broadly similar in age and design experience, drawn from a cohort with a male-female ratio of 3:1. No consent form was required for this experiment.