Creativity requires motivation; it does not happen passively. Our lives begin with biologic appetitive and aversive drives, such as the need to feed or avoid the cold. They are the roots of motivation.

In the 1950s, James Olds, Ph.D., showed that appetitive and aversive behaviors were controlled by distinct brain regions (J. Comp. Physiol. Psychol. 1954;47:419-27). He implanted electrodes into rat brains and placed the rats in a cage containing a foot switch that, when pressed, delivered an electrical shock to the brain region in which the electrode was implanted. By varying the location of the electrodes and the conditions under which rats were tested, Dr. Olds found that some regions and situations led to self-stimulation rates as high as 7,000 shocks per hour, and others led the rats to avoid self-stimulation. The size of the shock, fatigue, hunger, pain, hormonal levels, and drugs all influenced response rates.

Three brain regions, or systems, involved in motivation are the hypothalamus; the mesolimbic dopaminergic system (comprised of the ventral tegmental area [VTA], the nucleus accumbens/ventral striatum, and the orbitofrontal cortex [OFC], all linked together by the median forebrain bundle); and the amygdala. The hypothalamus maintains set points for different aspects of the "internal milieu," such as body weight and fluid balance. As our body strays from a set point, we are driven by hunger or thirst to alter our behavior and restore the set point. Returning our body to an established set point is powerfully rewarding. Within the mesolimbic system, VTA neurons generate a reward signal by comparing what occurs with what was expected (J. Neurophysiol. 1998;80:1-27). VTA dopaminergic reward neurons are most strongly activated by rewarding events that are better than expected.

The basolateral amygdala forms associations between sensory cues and rewarding or aversive stimuli, and acts as a "fear center" (J. Neurosci. 1995;15:5879-91). It is interconnected with sensory cortices and the hippocampus, forming associations with emotionally salient aspects of a stimulus that influence our perception and memory encoding of the stimulus (Curr. Opin. Neurobiol. 2004;14:198-202). Reward centers also modulate activity of the hypothalamus and locus ceruleus, thereby influencing endocrine and noradrenergic feedback to cortical regions.

The interplay of appetitive and aversive signals define a predicted, most rewarding (or least punishing) goal. Neurologists typically awaken early and perform a variety of duties over a long day (plus hospital call). Some appetitive signals include helping patients, research discoveries, educating students, pay, and benefits. Some aversive signals are the stresses of sick or otherwise difficult patients, research failures, underperforming students, and long hours. On balance, however, the net result is a greater feeling of reward than punishment so we keep doing it. But our behavior will change if discrepancies arise between the predicted and realized reward. If my health coverage were discontinued or my pay cut in half, I would seek a different position. The activity of anterior cingulate neurons – the earliest anatomical stage of action planning and movement – is influenced by reward signals from the orbitofrontal cortex. If a goal is made less rewarding, OFC neuronal activity declines as then does OFC stimulation of anterior cingulate neurons. The less rewarding activity stops and is replaced by a more rewarding one. Immediately preceding the change in behavior, specific neurons in the anterior cingulate fire, marking the first step that results in the altered response to the reduced reward (Science 1998;282:1335-8; Proc. Natl. Acad. Sci. U.S.A. 2002;99:523-8).

Our reward system has many targets defining our wants. These include biologic stimuli such as food when we are hungry; aesthetic stimuli such as humor, paintings, music, and sports cars; and money (Neuron 2001;30:619-39). Reward centers also are activated by socially relevant behaviors, such as the decision to enact justice-related punishment and social comparisons in which we may perceive ourselves as better off than our neighbor. The developing relationship between two people learning the degree to which they can trust one another also causes changes in reward center activity (detected by fMRI) in an interpersonally synchronized fashion (Science 2005;308:78-83).

Aversive stimuli, such as pain or the loss of money, activate similar brain regions, although specific areas differ from those activated by reward (Nat. Neurosci. 2001;4:95-102). Motivation is also attenuated by diminished reward, and by nonescalating, static reward. We quickly accommodate to any improvement in our life circumstances (for example a higher income) so that initially heightened satisfaction rapidly recalibrates to baseline (the hedonic treadmill).

These examples illustrate that there is a final common reward pathway. All appetitive and aversive stimuli are translated into a common biologically relevant motivational signal that tells us whether something will enhance or diminish our survival or quality of life. The perceived difference in reward value between what is and what should be generates the motivational voltage that drives creativity.

This column, "Evoked Potentials," regularly appears in Clinical Neurology News, an Elsevier publication. Dr. Caselli is the medical editor of Clinical Neurology News and is a professor of neurology at the Mayo Clinic Arizona in Scottsdale. E-mail Dr. Caselli.

Motivation Is the Driving Force in All We Do