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resonance imaging), EEG (electroencephalogram) and MEG (magnetoencephalography). Second, it would be important to understand the implications of the dendritic and axonal arbors for the mean electrical field and its several frequency components (gamma band, alpha band, and so forth) as measured in clinical and scientific studies in EEG and MEG. Third, it would be important to understand the relationship between neurotransmitter concentrations, such as aminolbutric acid (GABA) density measured using MR spectroscopy, and circuit properties, such as the peak oscillation and coherence bands. Finally, it would be important to have the ability to generate a computational model of a circuit with specific anatomy so that the simultaneous prediction of the fMRI signal, the EEG signal, and the two-photon calcium images from this same circuit is possible given a particular input.

To systematically understand the relationship of data at different scales, it is necessary to establish theories and mathematical models to link the data and to validate these models with experimental data from in vitro settings and in vivo settings with animal models and human subjects. For applications to disease, it is also necessary to include pathological alterations of these models. Although there have been ad hoc efforts to combine data from different modalities, a systematic approach—which may lead to groundbreaking methodologies and science—is lacking.

Key Questions

  • How do we establish a common computational language that might be used by investigators using these diverse technologies to measure neural circuitry and neural signals?

  • Can we identify some key model systems that would serve as a fruitful environment for combining these techniques? Can these be human, or does the basic work have to be done in animal systems?

  • How do we educate investigators who are principally involved in one technology—say fMRI or two-photon calcium imaging—in the biophysics and modeling techniques that would allow them to understand the related fields and contribute to the complete modeling effort?



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