Intrinsic signal imaging is a functional neuroimaging technique scientists use to observe brain activity. It operates by detecting minor changes in blood properties that occur when neurons are active. This indirect measurement allows for the visualization of activity over large areas of the brain’s cortex with high spatial precision.
The Mechanism of Intrinsic Signals
The foundation of intrinsic signal imaging is neurovascular coupling, the relationship between local neural activity and subsequent changes in cerebral blood flow. When a group of neurons becomes active, its metabolic demand increases, requiring more oxygen. To meet this demand, the brain increases its local blood supply in response to these shifts in functional activity.
Increased neuronal work leads to a consumption of oxygen from the surrounding blood, altering the local ratio of two types of hemoglobin. These are oxygenated hemoglobin (oxyhemoglobin), which carries oxygen, and deoxygenated hemoglobin (deoxyhemoglobin), which has released its oxygen. These two forms have different optical properties, and deoxygenated hemoglobin specifically absorbs more red light than oxygenated hemoglobin.
The change in light reflectance from the shifting concentration of these hemoglobin types is the “intrinsic signal” the technique measures. Active brain regions have a higher concentration of deoxyhemoglobin, causing them to reflect less light and appear slightly darker. This change is subtle, on the order of a 1% change in light reflectance.
Initially, neuron activation causes a rapid increase in oxygen consumption, leading to a brief increase in deoxyhemoglobin known as the “initial dip.” This is followed by a more significant and sustained increase in local blood flow, delivering an oversupply of oxygenated blood to the area. This subsequent phase is called functional hyperemia. The initial dip is thought to be more precisely localized to the area of actual neural activation.
How Brain Activity is Visualized
Visualizing brain activity with this technique is performed on animal models in a laboratory. The process begins with a surgical procedure to expose a small portion of the brain’s surface, or cortex. In some cases, imaging can be performed through a thinned skull, making the procedure less invasive.
The brain’s surface is illuminated with light of a specific wavelength, often in the red spectrum, to capture the absorption differences between hemoglobin types. A highly sensitive scientific camera is positioned above the cortex to record the light being reflected off the tissue. This camera can detect the small changes in reflectance that indicate neural activity.
The process uses a technique called differential imaging. First, an image of the cortex is captured in a resting state to establish a baseline. Then, a stimulus is presented to the animal, and another image is captured during this period of brain activity. The baseline image is digitally subtracted from the stimulation image, which cancels out static features like blood vessels and isolates the dynamic changes.
The resulting image highlights only the areas where reflectance changed, revealing the pattern of brain regions activated by the stimulus. Because the intrinsic signal is faint, multiple trials are often averaged together to improve the signal-to-noise ratio and generate a clear functional map.
Applications in Neuroscience Research
Intrinsic signal imaging helps neuroscientists understand the functional organization of the cerebral cortex. One of its primary applications is mapping functional columns, which are vertical columns of cells in the cortex that share similar response properties.
An example is the mapping of orientation columns in the primary visual cortex of animals like cats and monkeys. These are clusters of neurons that respond selectively to lines of a specific angle. Using ISI, researchers present stimuli of different orientations to create detailed maps showing how these columns are organized across the cortical surface.
Another application is studying the somatosensory cortex, particularly the “whisker barrels” in rodents. Each whisker on a rodent’s snout corresponds to a specific cluster of neurons in the brain called a barrel. ISI allows scientists to visualize these barrels, study their response to stimulation, and see how these maps change with experience (cortical plasticity).
The technique also reveals the functional architecture of other sensory systems, including mapping responses in the auditory cortex and olfactory bulb. This ability to map large cortical areas makes ISI a powerful tool for investigating brain organization and plasticity.
Relationship to Other Neuroimaging Methods
Intrinsic signal imaging is related to functional magnetic resonance imaging (fMRI), as both rely on changes in blood oxygenation. The fMRI signal, known as the blood-oxygen-level-dependent (BOLD) signal, is closely related to the intrinsic signals. ISI offers significantly higher spatial resolution, capable of resolving cortical columns too small for fMRI. However, ISI is invasive and limited to the brain’s surface, whereas fMRI is non-invasive and can image the entire brain.
Compared to electrophysiology techniques like microelectrode recordings, the strengths and weaknesses are reversed. Electrophysiology provides superior temporal resolution, measuring the electrical spikes of neurons in milliseconds, far faster than the slow hemodynamic response measured by ISI. An electrode, however, can only record from a small number of neurons. ISI provides excellent spatial coverage, capturing an activity map across a wide area of the cortex simultaneously.
These differences mean the techniques are complementary. For instance, ISI might be used to identify a functional area, which is then targeted with microelectrodes for detailed, high-speed recording. The choice of method depends on whether a researcher needs wide spatial detail (ISI), non-invasive whole-brain imaging (fMRI), or the precise timing of neuron firing (electrophysiology).