REVIEW ■ : Mapping Neuronal Activity by Imaging Intrinsic Optical Signals

Modern neuroimaging techniques use signals originating from microcirculation to map brain function. In this study, activity-dependent changes in oxyhemoglobin, deoxyhemoglobin, and light scattering were characterized by an imaging spectroscopy approach that offers high spatial, temporal, and spectral resolution. Sensory stimulation of cortical columns initiates tissue hypoxia and vascular responses that occur within the first 3 seconds and are highly localized to individual cortical columns. However, the later phase of the vascular response is less localized, spreading over distances of 3 to 5 millimeters.

Voltage-sensitive dyes allow neuronal activity to be studied by non-invasive optical techniques. They provide an attractive means of investigating striate cortex, where important response properties are organized in two dimensions. In the present study, patterns of ocular dominance and orientation selectivity were obtained repeatedly from the same patch of cortex using the dye merocyanine oxazolone, together with current image-processing techniques. The patterns observed agree with most established features of monkey striate cortex and suggest a new unit of cortical organization; one that is modular in structure and which appears to link the organization of orientation selectivity with that of ocular dominance.

We have shown previously the existence of small, activity-dependent changes in intrinsic optical properties of cortex that are useful for optical imaging of cortical functional architecture. In this study we introduce a higher resolution optical imaging system that offers spatial and temporal resolution exceeding that achieved by most alternative imaging techniques for imaging cortical functional architecture or for monitoring local changes in cerebral blood volume or oxygen saturation. In addition, we investigated the mechanisms responsible for the activity-dependent intrinsic signals evoked by sensory stimuli, and studied their origins and wavelength dependence. These studies enabled high-resolution visualization of cortical functional architecture at wavelengths ranging from 480 to 940 nm. With the use of near-infrared illumination it was possible to image cortical functional architecture through the intact dura or even through a thinned skull. In addition, the same imaging technique proved useful for imaging and discriminating sensory-evoked, activity-dependent changes in local blood volume and oxygen saturation (oxygen delivery). Illumination at 570 nm allowed imaging of activity-dependent blood volume increases, whereas at 600-630 nm, the predominant signal probably originated from activity-dependent oxygen delivery from capillaries. The onset of oxygen delivery started prior to the blood volume increase. Thus, optical imaging based on intrinsic signals is a minimally invasive procedure for monitoring short- and long-term changes in cerebral activity.