Advanced Optical Image Probe for Neurophysiology

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DESCRIPTION (provided by applicant): At the center of most diagnostic tests for human mental function is an imaging technique that visualizes activity patterns across the brain. In the near future, we can imagine the development of an examination table which non-invasively bathes the patient with electromagnetic waves, scanning for both structure and function, and creating three dimensional (3D) images or movies. Many such imaging techniques are available, including PET, MRI, MEG, EEG and optical techniques which offer a unique complement and significant advantages. Most optical methods visualize comparatively slow processes such as the changes in blood flow, volume and oxygenation that accompany metabolic activation of neural tissue. Changes in light absorbance associated with metabolic and hemodynamic processes are robust and relatively easy to obtain non-invasively, but spatial and temporal resolution is limited by the anatomy and physiological regulation of cerebral perfusion. We have observed very fast optical changes in rat somatosensory cortex that are directly related to the evoked electrical response and to a fast (200-600 Hz) oscillation that accompanies the evoked response. Such in-vivo signals are small compared to noise, often requiring 1000 to 4000 averages, and preclude dynamic studies of neural activation. Our principal aim is to investigate the biophysical mechanisms of fast optical signals and to improve the signal-to-noise ratio in mammalian neural tissue. To accomplish this aim we will pursue 3 specific aims. First, we will test the hypothesis that confocal birefringence illumination will enhance the faster optical signals over the slower hemodynamic components traditionally seen with bright-field illumination. Our second aim will test the hypothesis that the early components of the fast optical signals will localize specifically to the cortical column. Within our third aim, we will test the hypothesis that birefringence signals originate from a change in refractive index due to cellular swelling and will follow voltage sensitive dye and membrane potentials. Over the past 3 years we have significantly improved the utility of optical measurements for recording fast neurophysiological events. Accomplishment of these new goals is crucial to moving optical techniques into more practical applications that image electrical correlates of neural activity with better signal-to-noise.