Functional Optical Imaging of Intrinsic Signals in Cerebral Cortex

In the early nineteenth century, Franz Gall, a Germanborn physician and neuroanatomist who studied and worked in Vienna, proposed that specific functions or behaviors are controlled by particular regions of the cerebral cortex. Although Gall extended this proposition to develop the (incorrect) doctrine of phrenology, it was the first account of localization of function in the cerebral cortex. Forty years later Gall’s ideas were extended by Paul Pierre Broca, who in 1861 published an account of a patient who could understand language but could not speak. Postmortem examination of the patient’s brain showed a lesion in the posterior area of the frontal lobes, an area that has become known as Broca’s area. This intriguing finding led to the search for more functionally distinct regions of the cerebral cortex and, in 1870, Fritsch and Hitzig reported that electrically stimulating the precentral gyrus in the dog resulted in movements of the contralateral limb. Fritsch and Hitzig had found what is now known as the primary motor cortex. Investigation of localized functional regions of the cerebral cortex increased at a rapid pace and by the mid-twentieth century it was well established that the cerebral cortex could be divided into discrete regions on the basis of cytoarchitectonics (type, density, and layering of cells) and physiological function. Localization of function in the cerebral cortex is perhaps best demonstrated in the mammalian visual cortex, where in the primate and presumably the human, more than 30 distinct cortical regions associated with the analysis of visual information exist. The localization of function in the cerebral cortex has traditionally relied on techniques such as lesion studies, neuroanatomical tract tracing and single-cell electrophysiology in animal-based experiments, or on clinical studies where behavioral symptoms are correlated with postmortem findings of underlying cortical pathology or where specific regions of the cerebral cortex are electrically stimulated during neurosurgical procedures for disorders such as epilepsy. In addition to these techniques, a number of imaging techniques are now available, including positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and optical imaging of intrinsic signals (OIIS). In functional imaging of the cerebral cortex, the relationship between regional cerebral blood flow (rCBF) and function is exploited to correlate localized cortical activity with physiological function. OIIS is a minimally invasive means of determining patterns of neural activity over large areas of the cortex (typically on the order of 25mm) with resolution as fine as tens of micrometers. The signal is manifest as a darkening of the cortex; that is, it occurs when the light absorption of the tissue increases and its reflectance decreases. These light-related phenomena closely correlate with underlying neural activity and are largely because of the fact that cerebral blood flow (CBF) and energy metabolism are regulated at such a fine scale.