Non-electrophysiological methods of the visualization. Two- and three dimensional visualization (optical imaging of the brain surface).

The systematic combination of anatomical, physiological, and computational techniques confirmed the concept of mapping during the second half of the 20th century. Motor and sensor “homunculus” at the human brain is one of the most common example of the functional map of the cortex (see below).

Neuroimaging includes the use of various techniques to either directly or indirectly image the function of the brain. It is a relatively new discipline within medicine and neuroscience. Functional imaging is used to diagnose metabolic diseases and lesions on a finer scale (such as Alzheimer's disease) and also for neurological and cognitive science research and building brain-computer interfaces. Functional imaging enables, for example, the processing of information by centers in the brain to be visualized directly. Such processing causes the involved area of the brain to increase metabolism and "light up" on the scan. Neuroimaging falls into two broad categories: invasive and non-invasive. Non-invasive methods iclude fMRI (functional magnetic resonancse imaging), PET (positrone –emission tomograpgy), SPECT (single photon emission computed tomography), DOT (diffuse optical imaging). Invasive include IOS (intrinsic optical imaging), VSD and CSD (voltage- and calcium sensitive dye imaging) ( , and some other methods.

Functional Magnetic Resonance Imaging (fMRI) relies on the paramagnetic properties of oxygenated and deoxygenated hemoglobin to see images of changing blood flow in the brain associated with neural activity. This allows images to be generated that reflect which brain structures are activated (and how) during performance of different tasks. Most fMRI scanners allow subjects to be presented with different visual images, sounds and touch stimuli, and to make different actions such as pressing a button or moving a joystick. Consequently fMRI can be used to reveal brain structures and processes associated with perception, thought and action. The resolution of fMRI is about two or three millimeters at present, limited by the spatial spread of the hemodynamic response to neural activity. It has largely superseded PET for the study of brain activation patterns. PET, however, retains the significant advantage of being able to identify specific brain receptors (or transporters) associated with particular neurotransmitters through its ability to image radiolabelled receptor "ligands" (receptor ligands are any chemicals which stick to receptors).

As well as research in healthy subjects, fMRI is increasingly used in medical diagnosis of disease. Because fMRI is exquisitely sensitive to blood flow, it is extremely sensitive to early changes in the brain resulting from ischemia (abnormally low blood flow), such as the changes which follow stroke. Early diagnosis of certain types of stroke is increasingly important in neurology, since substances which dissolve clots may be used in the first few hours after certain types of stroke occur, but are dangerous to use afterwards. Brain changes seen on fMRI may help to make the decision to treat with these agents.

Positron Emission Tomography (PET) measures emissions from radioactively labeled metabolically active chemicals that have been injected into the bloodstream and uses the data to produce two or three-dimensional images of the distribution of the chemicals throughout the brain (Nilsson 57). The positron emitting radioisotopes used are produced by a cyclotron and chemicals are labelled with these radioactive atoms. The labeled compound, called a radiotracer, is injected into the bloodstream and eventually makes its way to the brain. Sensors in the PET scanner detect the radioactivity as the compound accumulates in different regions of the brain. A computer uses the data gathered by the sensors to create multicolored two or three-dimensional images that show where the compound acts in the brain. Especially useful are a wide array of ligands used to map different aspects of neurotransmitter activity.

The greatest benefit of PET scanning is that different compounds can show blood flow and oxygen and glucose metabolism in the tissues of the working brain. These measurements reflect the amount of brain activity in the various regions of the brain and allow us to learn more about how the brain works. PET scans were superior to all other metabolic imaging methods in terms of resolution and speed of completion (as little as 30 seconds), when they first became available. The improved resolution permitted better study to be made as to the area of the brain activated by a particular task. The biggest drawback of PET scanning is that because the radioactivity decays rapidly, it is limited to monitoring short tasks (Nilsson 60). Before fMRI technology came online, PET scanning was the preferred method of brain imaging, and it still continues to make large contributions to neuroscience.

PET scanning is also used for diagnosis of brain disease, most notably because brain tumors, strokes, and neuron-damaging diseases which cause dementia (such as Alzheimer's disease) all cause great changes in brain metabolism, which in turn causes easily detectable changes in PET scans.

Single Photon Emission Computed Tomography (SPECT) is similar to PET and uses gamma ray emitting radioisotopes and a gamma camera to record data that a computer uses to construct two- or three-dimensional images of active brain regions (Ball). SPECT relies on an injection of radioactive tracer, which is rapidly taken up by the brain but does not redistribute. Uptake of SPECT agent is nearly 100% complete within 30 – 60s, reflecting cerebral blood flow (CBF) at the time of injection. These properties of SPECT make it particularly well suited for epilepsy imaging, which is usually made difficult by problems with patient movement and variable seizure types. SPECT provides a "snapshot" of cerebral blood flow since scans can be acquired after seizure termination (so long as the radioactive tracer was injected at the time of the seizure). A significant limitation of SPECT is its poor resolution (about 1 cm) compared to that of MRI.

Like PET, SPECT also can be used to differentiate different kinds of disease process which produce dementia, and it is increasingly used for this purpose. Neuro-PET has a disadvantage of requiring use of a tracers with half-lives of at most 110 minutes, such as FDG. These must be made in a cyclotron, and are expensive or even unavailable if necessary transport times are prolonged more than a few half-lives. SPECT, however, is able to make use of tracers with much longer half-lives, such as technetium-99m, and as a result, is far more widely available.

Diffuse Optical Imaging (DOI) or Diffuse Optical Tomography (DOT) is a medical imaging modality which uses near-infrared light to generate images of the body. The technique measures the optical absorption of haemoglobin, and relies on the absorption spectrum of haemoglobin varying with its oxygenation status.

The very goof example of the vizualization of function is a 2-deoxyglucose. Principle of the method: Radioactive 2-deoxyglucose is taken up by active neurons via the glucose transporter, yet not metabolized. Radioactivity accumulates in active cells. Specimen are freeze dried, sectioned and activity is subsequently recorded by autoradiography. Neuronal activity depends on previous stimulus conditions, see example below:

Deoxyglucose (top, left) staining marks the regions of activity in histological preparations: eye of origin, for instance, is organised in stripes (demonstrated by monocular stimulation): ‘ocular dominance maps’ (bottom, left) and location in the visual field is organised in 'retinotopic maps’ (right)