Sometimes the discoveries most exciting to read about are those that were made long ago, due to the sheer advance in knowledge that they represented. Such classic studies also remind us that the most important discoveries can be made with even the most rudimentary techniques, when combined with careful observation and clever interpretation. In 1954, James Olds and Peter Milner of McGill University published a seminal paper in which they report evidence for the existence of a reward center in the brain. In the paper, Olds and Milner describe their finding that rats would continually press a lever in return for receiving nothing more than a brief pulse of electrical stimulation in a particular region of the rat’s brain called the septal area. Since electrical stimulation in the septal area was all that was needed to reinforce the lever-pressing behavior, and since the rate of reinforcement was comparable to that produced by natural rewards, the authors inferred that stimulation in this brain area was somehow rewarding or reinforcing in of itself.
The septal area is a region in the middle of the brain, just above the hypothalamus, which is composed of several subgroups of neurons, and is thought to be a key player in the limbic system, an interconnected network of structures involved in emotion. Olds and Milner’s experiments provided some of the first key evidence for the existence of certain regions in the brain that process reward, or positive reinforcement.
Here’s how the experiment was performed: rats were placed in a “large-levered Skinner box” (Operant Conditioning Chamber) on 2 consecutive days and were subjected to both an ‘acquisition’ period and an ‘extinction’ period. During the 3-hour acquisition period, whenever the rat pressed a lever it would connect a circuit and activate current flow into an electrode placed at a particular location in the rat’s brain. Then, during the 30-minute extinction period, the lever was deprived of its special stimulatory powers; when the rat pressed the lever, no current would flow.
During both the acquisition and extinction periods, the percentage of time that rats spent lever-pressing was recorded. (This percentage measurement was calculated by determining whether or not a rat had pressed a lever at least once during a given 30 second interval.)
Olds and Milner then determined whether rats pressed the lever at different rates during the acquisition phase compared to the extinction phase, and asked whether this was related to the specific brain area being stimulated. They reasoned that if the rats pressed at higher rates during acquisition, then stimulation of this brain area must reflect some type of positive, rewarding sensation for the rat. This result would indicate that they had found a reinforcement center in the brain. On the other hand, if the rat pressed at lower rates when receiving stimulation, then the electrode was probably stimulating a punishment center in the brain. And if the rat’s lever-pressing behavior didn’t seem to change based on whether the lever was hooked up to electrical brain stimulation, well, maybe that region was not particularly relevant to the processing of reward or aversion.
The results are summarized plainly in the paper as follows: “there are numerous places in the lower centers of the brain where electrical stimulation is rewarding in the sense that the experimental animal will stimulate itself in these places frequently and regularly for long periods of time if permitted to do so.” The anatomical location of the “regions in the lower centers of the brain” that the authors describe maps well to the aforementioned septal area. It turned out that a similar effect was also produced when the electrodes were implanted in the nearby Nucleus Accumbens (Olds 1956, Scientific American). We now know that the Nucleus Accumbens is one of the principal regions in which the neurotransmitter dopamine is released, and is implicated in the response to natural rewards and to drugs of abuse such as cocaine (Luscher and Malenka 2011 Neuron).
The significance of Olds and Milner’s finding is stated by the authors in beautifully simple and clear language as follows: “In septal area preparations, the control exercised over the animal’s behavior by means of this reward is extreme, possibly exceeding that exercised by any other reward previously used in animal experimentation.”
Olds and Milner also note, “there are also sites in the lower centers where the effect is just the opposite: animals do everything possible to avoid stimulation.” This observation hints at the existence of centers in the brain whose stimulation produces the experience of punishment, or aversion. Finally, there were many “neutral sites”, where electrical stimulation had no effect on lever pressing.
Today, there are many papers that carefully delineate neural pathways involved in the processing of reward and aversion. And just as the canon of knowledge on this subject has advanced, so have the experimental techniques used to make these increasingly more detailed discoveries. Today, with techniques such as optogenetics, we can stimulate the activity of specific types neurons in very small, carefully targeted brain regions, and we have extremely precise control over the rate of activity in individual neurons. We have come a long way from sticking a giant electrode in a rat brain and passing current.
All of this technical mastery that we have access to today is absolutely necessary because it turns out that many of the circuits in the brain are so tightly intermingled and complex they require all the tools afforded by modern neuroscience. For instance, here at Stanford, the Malenka and Deisseroth labs are doing incredible work to both innovate such experimental tools and use them to dissect reward and aversive brain circuitry, which I plan to discuss more in future posts. As is apparent from the work of these and other labs, the pathways of reward and aversion in the brain are turning out to be much more nuanced than what was initially reported in this pioneering study on the topic.
And yet, this original principle, that the behavioral effects of reward and aversion are associated with activity in specific physical locations in the brain, was established a long time ago, as evidenced by this classic paper by Olds and Milner. In some abstract sense, the rest is just commentary.