Brain Metabolsm and Brain Function

The brain is active all the time, not only in wakefulness but also in sleep. Therefore, it, like the heart, is criticallyin need of a continuous supply of metabolic fuel substances (energy) and oxygen provided by the blood flow.


In contrast to other active body organs (e.g., heart, muscle), which utilize alternative fuels like the fatty acids, the brain under normal conditions, depends almost exclusively on glucose to obtain its energy needs. Marked hypoglycemia (e.g., due to a large insulin dose) may lead to fainting, convulsions, coma, or death. Interestingly, after days of starvation, the brain develops the capacity (enzymes) to use ketone bodies (a product of fatty acid metabolism in the liver) as an alternative energy source. This capacity is present in the newborn brain but disappears after infancy. The brain’s critical dependency on glucose is one of the bases for the existence of many regulatory mechanisms for blood glucose homeostasis.

To produce the large quantity of ATP required by brain cells, the Kreb’s cycle / oxidative phosphorylation pathway is utilized. This acccounts for the brain’s high and critical dependence on oxygen. In adults, 10 seconds of anoxia (oxygen deprivation) is sufficient to lose consciousness and higher brain functions (fainting). A few minutes of hypoxia can lead to coma and severe and irreversible brain damage; death can occur due to the loss of function in the vital respiratory centers of the medulla.

In adults, brain weight is about 1.4 kg (3 lbs), and the brain has an oxygen consumption rate of about 50 cc per min. Thus, although the brain’s weight is only 2% of the body’s, its oxygen consumption rate (metabolic rate) is about 20% of the whole body’s. Why does the brain require such a high metabolic rate? Its work depends heavily on formation, propagation, synaptic transmission, and integration of a variety of electrochemical potentials, cellular functions requiring the maintenance of proper ionic gradients. To do this, the brain cell membranes contain one of the largest concentrations of sodium-potassium pumps in the body. These pumps are ATP dependent; they involve the operation of the plasma membrane enzyme Na-K-ATPase, which is also present in the brain in large concentrations. The sodium pump uses most of the ATP produced in the brain.

In neurons, the synapses on dendrites and cell bodies use the greatest amoung of energy. Therefore, the synapse rich areas (e.g., the gray matter (cortex, basal ganglia, and subcortical nuclei) have generally high metabolic rates, and synapse-poor areas (e.g. the fatty white matter myleninated nerve fibers) have low rates. Among the gray matter areas, relative rates vary. The forebrain basal ganglia and the mid brain interior colliculi show very high rates; the cortex of the cerebrum and cerebellum have moderately high rates; the thalamus and the nuclei of the cerebullum and medulla show medium rates; the lowest rates are associated with spinal cord white matter.

BRAIN BLOOD FLOW: To support its high oxygen and glucose needs, the brain has an extensive vascular supply and a very efficient blood flow regulation system. Normal blood flow to the brain is fairly high (750 ml/min), amounting to 15% of the body’s. Blood flow in different brain regions is regulated by poorly understood local (intrinsic to the brain) factors. In general, increase in neural activity in a particular brain area results in a rapid increase in local blood flow in that area, presumably to supply the excess needs for oxygen and glucose and to remove the excess metabolities (acid and carbon dioxide).


The direct relation between an area’s neural activity and blood flow has recently been utilized to map the brain’s functional regions (mainly brain cortex) in conscious, responsive human subjects. A subject is injected with an inert radioactive gas such as xenon. As the blood flows through the various brain regions, detectors in a helmet worn on the head measure the radioactivity. These studies revealed that regional brain-blood flow pattern (hence neural activity) is dynamic changing depending on physiological and psychological conditions.

For example, at rest, only the frontal lobes, particularlly the premotor regions, show higher than average activity. During bodily or mental activity, depending on the task involved, the regional activity pattern changes. Thus, clenching of right hand increased activity in both the sensory and motor hand areas, although more in the left than right hemisphere. Sensory stimulation of the hand alone, however, increases activity mostly in the sensory areas. Interestingly, whereas simple pronouncement of words increases activity mainly in the primary sensory / motor speech areas of both hemispheres (lips, tongue, face), creative speech involviing thinking and ideas also increases activity in the Wernicke’s and Broca’s speech areas of the left hemisphere. Reading increases activity in a large area of the brain, including not only the expected visual and visual association areas but also the parieto-temporal areas, including the Wernicke’s area, which are involved in word comprehension. Activity in the frontal lobes is increased not only during contemplation, problem solving, and planning, but also during pain and anxiety.

Certain mental disorders such as schizophrenia and depression and the senile disorders such as dementias (reduced cognitive and memory capacities) are associated with reduced blood flow/metabolic activity. Brain diseases such as epilepsy, in which convulsions are observed due to excessive electrical activity, are associated with increased blood flow and metabolic activity.

Daryl Conant, M.Ed