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Improving Resolution. 
Many new brain-scanning technologies now in development are dramatically improving both 
temporal and spatial resolution. This new generation of sensing and scanning systems is providing the tools needed to 
develop models with unprecedented fine levels of detail. Following is a small sample of these emerging imaging and 
sensing systems. 
One particularly exciting new scanning camera is being developed at the University of Pennsylvania 
Neuroengineering Research Laboratory, led by Leif H. Pinkel.
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The optical system's projected spatial resolution will 
be high enough to image individual neurons and at one-millisecond time resolution, which is sufficient to record the 
firing of each neuron. 
Initial versions are able to scan about one hundred cells simultaneously, at a depth of up to ten microns from the 
camera. A future version will image up to one thousand simultaneous cells, at a distance of up to 150 microns from the 
camera and at submillisecond time resolution. The system can scan neural tissue in vivo (in a living brain) while an 
animal is engaged in a mental task, although the brain surface must be exposed. The neural tissue is stained to generate 
voltage-dependent fluorescence, which is picked up by the high-resolution camera. The scanning system will be used 
to examine the brains of animals before and after they learn specific perceptual skills. This system combines the fast 
(one millisecond) temporary resolution of MEG while being able to image individual neurons and connections. 
Methods have also been developed to noninvasively activate neurons or even a specific part of a neuron in a 
temporally and spatially precise manner. One approach, involving photons, uses a direct "two-photon" excitation, 
called "two-photon laser scanning microscopy" (TPLSM).
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This creates a single point of focus in three-dimensional 
space that allows very high-resolution scanning. It utilizes laser pulses lasting only one millionth of one billionth of a 
second (10
–15
second) to detect the excitation of single synapses in the intact brain by measuring the intracellular 
calcium accumulation associated with the activation of synaptic receptors.
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Although the method destroys an 

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insignificant amount of tissue, it provides extremely high-resolution images of individual dendritic spines and 
synapses in action. 
This technique has been used to perform ultraprecise intracellular surgery. Physicist Eric Mazur and his 
colleagues at Harvard University have demonstrated its ability to execute precise modifications of cells, such as 
severing an interneuronal connection or destroying a single mitochondrion (the cell's energy source) without affecting 
other cellular components. "It generates the heat of the sun," says Mazur's colleague Donald Ingber, "but only for 
quintillionths of a second, and in a very small space." 
Another technique, called "multielectrode recording," uses an array of electrodes to record simultaneously the 
activity of a large number of neurons with very high (submillisecond) temporal resolution.
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Also, a noninvasive 
technique called second-harmonic generation (SHG) microscopy is able "to study cells in action," explains lead 
developer Daniel Dombeck, a graduate student at Cornell University. Yet another technique, called optical coherence 
imaging (OCI), uses coherent light (lightwaves that are all aligned in the same phase) to create holographic three-
dimensional images of cell clusters.