The amygdala, a part of the known for its role in , also helps people spot rewards — and go after them By Susan Gaidos Cerebral Delights ou know the feeling — the flush Those clumps of cells, one on each side in response to all sorts of stimuli, bad and of excitement when your boss of the brain, are known as the amygdala good. It plays a role not only in aversion hands you a bonus check, or (uh-MIG-duh-luh). For years the amyg- to fright, but also in pursuit of pleasure. you unexpectedly run into an dala has been regarded primarily as the Studies of the brain’s anatomy reveal Yold friend, or you discover a way to get brain’s center for fear. Scores of studies good reasons for the amygdala’s power: tickets to the big game that was long ago have shown that it is essential both for It is very well connected. In humans and sold out. When life throws you a gift or perceiving fear and expressing it. other primates, the amygdala is linked a gain, it’s not just your mood that perks In recent years, though, a surge of new through a complex network of cells to ORGENSTERN

up. Two small -shaped masses research has expanded scientists’ view of brain regions involved in all five senses. M of nerve cells buried deep in your brain the amygdala’s importance. It turns out Signals about everything you encoun-

take notice too. that the amygdala helps shape behavior ter are passed from the brain’s sensory MICHAEL

22 | SCIENCE NEWS | February 26, 2011 www.sciencenews.org Sensory cortices processing areas directly to the amyg- system, alerting the body to respond. dala. And the amygdala shares elaborate Chemical messengers are then 3 Anterior communications channels with the pre- released into the bloodstream to cingulate frontal cortex — the brain’s control center ready a flight-or-fight response, cortex 4 Central for planning and decision making. providing the energy needed to 2 Sensory Orbitofrontal cortices Its strategic location allows the amyg- run faster or hit harder. cortex 7 dala to act as a spotlight, calling attention Early humans relied 1 Intercalated 5 Prefrontal masses Lateral to sensory input that is new, exciting and on this system to avoid cortex 6 nucleus important. In this way, it helps predict the all types of deadly threats, Basal and timing and location of potential dangers, from saber-toothed tigers to accessory Amygdala 8 basal nuclei helping you dodge many of the things you falling trees. dread. But those same connections also But being able to identify Autonomic help you acquire the good things in life, by potential rewards is also crucial Hormonal responses nervous system

identifying and assessing rewards such as for survival, says Elisabeth Murray, a Inhibitory Excitatory food, sex and other delights. neurobiologist at the National Insti- connections connections Though much more is known about tute of Mental Health in Bethesda, Md. Linked in Two clumps of cells, one its fear job, researchers are now vigor- People, and other animals, face count- on each side of the brain, the amyg- ously gathering evidence about how the less reward-related decisions as they dala has many connections with amygdala evaluates information and go about their daily business, foraging parts of the and events for their reward potential. Recent for food, finding mates and passing on brain areas involved in the senses. studies offer clues to how the amygdala genes. Identifying pleasant situations assigns value to rewards and adjusts and avoiding aversive ones can boost 1. A s the brain’s command center, the prefrontal cortex is responsible for that value as circumstances change. well-being and chances for survival. making social choices, predicting Other work provides insights into how Murray says many scientists are now future events, planning behavior and the amygdala links actions and rewards, coming to understand that at least part controlling . suggesting that the amygdala plays a role of that reward-based behavior is driven 2. A part of the prefrontal cortex, the appears to be in goal-directed behavior. Still others are by some sort of interaction between the active during sensory integration finding out how neural circuits in the amygdala and the , known and decision making. highly connected human amygdala work to be involved in thought, and 3. The anterior with other brain structures to recognize consciousness. Her lab is especially plays a role in attention, motivation and error detection. good things and find ways to get them. interested in circuits connecting the 4. T he amygdala’s central nucleus is Such studies may help scientists amygdala with the orbitofrontal cortex, involved in fear responses, including understand how rewards can sway atten- a part of the prefrontal cortex that sits freezing in place, rapid heartbeat tion or learning and help people make just behind the eyes. and increased respiration. It is also linked with -hormone release. choices. Recent results may also lead to “Those parts of the brain are ana- 5. After receiving information from the new therapies for those suffering from tomically interconnected, and we think senses, the lateral nucleus forms depression and disorders, as well that they’re interconnected in this way associations with . as providing insights into reward-seek- to help animals make good decisions,” 6. Clusters of nerve cells, the basal ing behaviors such as addiction. Murray says. nuclei and accessory basal nuclei are responsible for body movement In recent years, Murray and others and coordination. Recognizing reward have initiated studies to better under- 2010 7. The intercalated masses are cell The amygdala is part of the limbic sys- stand how the amygdala processes infor- groups thought to play a role in tem, a primitive set of brain structures mation that feeds into decisions. emotional learning and memory. involved in and . Stud- In 2006, researchers at Columbia Uni- 8. T he hippocampus plays an impor- tant part in learning and memory. ies going back to the mid-1950s show versity provided a clue, showing how the that the amygdala, located near the amygdala judges the emotional value of hippocampus in the front part of the tem- stimuli. A team led by C. Daniel Salzman handle positive and negative events. poral lobe, serves as a type of watchdog taught monkeys to associate two patterns In a follow-up experiment with a ANNUAL REVIEW OF NEUROSCIENCE ANNUAL to identify potential threats and danger. on a TV monitor with either a rewarding slightly different setup, Salzman’s group USI/ F . S

Because it is highly interconnected with sip of water or an irksome puff of air to found that a set of nerve cells is spe- D the senses, the amygdala can take in dan- the face. By recording the electrical activ- cifically tuned for processing surprise. AN

M ger signals — the sight of a snake or the ity in the amygdala as animals watched Some among those nerve cells were ded- sound of a gunshot — and flash messages the screen, the scientists showed that dif- icated solely to the rewarding surprise, .D. SALZ

C almost instantly through the nervous ferent amygdala nerve cells are tuned to the water sip.

www.sciencenews.org February 26, 2011 | SCIENCE NEWS | 23 FEATURE | CEREBRAL DELIGHTS

“These neurons were not registering The third card reveals the exact same 10 on the fly. “If you’re an animal out there whether something aversive was surpris- of hearts. While golden in the first hand, and you’ve just learned something about ing,” Salzman says, suggesting they play a the 10 becomes an unfortunate deal the either a harmful stimulus or a predator, specialized role in rewarding surprises. second time around. Most people would you may not get a second chance.” Other amygdala neurons did the oppo- have no difficulty recognizing this point, Murray’s group is now using a simi- site — registering surprise when it was Salzman says, evidence that the amyg- lar method to see how values assigned aversive but not rewarding. By carrying dala’s emotional response to the same to various rewards can be linked with two different sets of neurons for sur- sensory stimulus can be flexible. actions. In a recent experiment, Sarah prise, the amygdala may be better able Murray sees such flexibility among Rhodes, also of the National Institute to predict what’s coming in order to pre- monkeys making food choices in the lab. of Mental Health, trained monkeys to pare appropriate actions, Salzman says. Given a choice between two perform two actions, tap and “If you get something that’s highly foods, monkeys (like most “I’m kind of hold, to receive a reward. Six rewarding by surprise, you want to be people) will invariably reach glad that the rapid taps to a touch-sensi- able to take actions in advance that for their favorite. But after brain isn’t as tive screen were rewarded would help you acquire that rewarding gorging on a favored food simple as we with one kind of food, while stimulus again,” he says. “By contrast, if for a while, the reward value a continuous touch for two you receive a bad surprise you normally of that treat diminishes, the sometimes seconds was rewarded with would want to take some defensive way the value of the 10 drops make it out another. actions or avoidance actions to avert a when a blackjack player to be.” Rhodes, Murray and their similar outcome.” already has 15 points in hand. colleagues wanted to see if PETER RUDEBECK At that point the monkeys the animals, once filled with Ensuring a good hand shift their choices and select a new food. their favorite food, would shift their But the same stimulus, depending on the Monkeys without a working amygdala, actions along with their choices. Nor- circumstances, can be rewarding or not, however, show little change in behavior mal monkeys did, choosing a new action Salzman explains. He uses an example and continue to stuff themselves with once they got their fill of the first food. from the card game blackjack. the first food choice, Murray’s studies Animals without an amygdala, however, The object of the game is to hold have found. These findings suggest that didn’t make the switch. cards with a total value as close as pos- the amygdala is needed to revise the Those findings, reported in November sible to 21, without going over. Players assessment of a reward’s value. in San Diego at the annual meeting of the are initially dealt two cards and then can “What we think is happening is that Society for Neuroscience, suggest that the request additional cards. the amygdala is helping updateReward the trials food intact control animals engaged in goal- Say a player is dealt two cards with value, and sending thatAir-puff information trials directed behavior, and that the amygdala a total value of 11 and then gets a 10 of somewhere else — probably the orbito- played a role, Murray says. hearts, worth 10 points, to reach a perfect frontal cortex,” Murray says. This same “It means the animals literally know 21. Now suppose that in the next hand, circuitry may also help animals, includ- and somehow represent a goal. And that after the cards are shuffled, the same ing humans, automatically calculate and if the value of the goal changes, they can player is dealt two cards that total 15. update the value of goals or outcomes therefore change their behavior,” she says. “We think this is what humans do, Cell-by-cell responses Different nerve cells in the amygdala respond differently depending so it’s really helpful to understand the 2010 on the stimulus. A study in monkeys found that while one set0 of cells1 (A) responded2 more3 robustly4 neural circuitry.” to a reward, a sip of water, another (B) responded more to an annoying puff of air. Another recent study shows that Neuron set A response to stimuli Neuron set B response to stimuli people, like monkeys, do indeed use the amygdala to judge the value of a par- Reward trials Reward trials ticular item. Rick Jenison, who studies Air-puff trials Air-puff trials neuroeconomics at the University of Wisconsin–Madison, and his colleagues recruited three volunteers who were CURRENT OPINION IN NEUROBIOLOGY AN/ already undergoing a procedure that M required electrodes to be implanted in the .D. SALZ C brain. Using the electrodes, the research- D Neural response Neural response Neural ers eavesdropped on 51 amygdala nerve cells as the volunteers put price tags on a ORRISON AN

0 1 2 3 4 0 1 2 3 4 series of junk food items. M . E .

Time from stimulus onset (seconds) Time from stimulus onset (seconds) Listening in on nerve cell chatter, S

24 | SCIENCE NEWS | February 26, 2011 www.sciencenews.org

Reward trials Air-puff trials

0 1 2 3 4 Right amygdala Jenison’s group found 16 individual cells rate in response to an expected reward. that responded in a way consistent with When looking at the animals’ emo- the values that participants assigned to tional responses — as measured by pupil individual foods. The study, published diameter and heart rate — researchers January 5 in the Journal of Neuroscience, found that monkeys without a working Electrode is the first to show how single neurons in location amygdala didn’t react to a reward in the human amygdala work to assess the the typical way, Rudebeck says. “They value of an object (SN: 1/29/11, p. 8). In Nerve cell response during value rating seemed to have no idea of what reward addition, the study shows how amyg- was, despite the fact that they could still Spike rates dala neurons compute value in real time, choose perfectly well.” 25 Presentation of stimuli while decisions are being made. The findings, reported at the neuro- “These findings suggest that the science meeting, suggest that the brain human amygdala’s involvement in deci- uses various mechanisms to calculate sion making happens at the time of the 15 how much something is worth. While the choice and is not restricted to familiar amygdala may be important for assign- situations,” he says. ing an emotional value, Rudebeck says, Many of the animal studies, on the 5 it may not be the “be-all and end-all” in other hand, are based on learned tasks, so second) per (spikes rate Discharge valuing objects. “I’m kind of glad that the 60 65 70 75 80 85 value could be assigned over a number of brain isn’t as simple as we sometimes Time (seconds) trials, Jenison says. make it out to be,” he says. Using functional MRI to map the loca- Tracking chatter By monitoring nerve By understanding how the amygdala cell activity in patients as they rated the value tion of the electrodes, Jenison’s group of various junk foods, researchers were able guides reward-based behavior, scientists created an anatomical map showing to locate speci"c cells in the amygdala whose hope to someday reap rewards of their the precise location of the value-coding responses corresponded with value ratings. own. A deeper knowledge of the neu- The graph shows how one neuron’s "ring rate neurons. Such information may serve as (electrode location shown above) peaked ral circuitry that regulates emotional a starting point in figuring out how such after junk foods were presented. responses may help scientists under- neurons connect to other structures in stand what goes awry in addiction and the brain. these other parts of the brain what these may allow scientists to find new ways to Because value-coding neurons in the certain things are worth. But we wanted intervene in times of distress. amygdala intermingle with neurons that to test that.” New discoveries could lead to medi- do other things, sorting out connections Rudebeck and his group trained cations and therapies designed to treat could be crucial for understanding how monkeys to play a computer game in mood disorders such as depression, people respond to particular cues, says which they assessed the value of differ- where stimuli that were previously neuroscientist Patricia Janak of the Uni- ent rewards. The animals were shown pleasing aren’t anymore, says Salzman. versity of California, San Francisco, who two different pictures and allowed to The studies also hold hope for develop- studies the amygdala’s role in reward choose between them. One picture ing new therapies for anxiety disorders, and addiction. “The idea would be to brought a large juice reward, and the and panic disorders that involve see where those [value-coding] neurons other brought a much smaller amount stimuli that can generate emotional are going, and then hence what behavior of juice. The animals chose the picture responses even when they are presented they ,” she says. associated with the larger reward more in a nontraumatic situation. than 98 percent of the time. “I believe that the best generation of Untangling connections After turning off the amygdala in some psychiatric treatments is still to come,”

2011 While recent studies show that the animals, the scientists used single-cell Salzman says. “And it will ultimately be amygdala plays a role in assigning value recordings to listen in on brain cell based on elucidation of the intercon- to actions or things, other findings show chatter in the orbitofrontal cortex and nected circuitry involving the amygdala, that parts of the prefrontal cortex also anterior cingulate cortex. To the team’s the prefrontal cortex and other brain signal what things are worth. surprise, the monkeys still chose the pic- structures.” s “We were really interested to know: Is ture with the “best” outcome on pretty the amygdala the thing which supplies much every trial, just as they had done Explore more

ET AL/JOURNAL OF NEUROSCIENCE AL/JOURNAL OF NEUROSCIENCE ET that value information or is it the other with a working amygdala. s C.D. Salzman and S. Fusi. “Emotion, way around — the prefrontal cortex that Though the animals continued choos- Cognition, and Mental State Repre- tells the amygdala?” says Peter Rudebeck, ing in the same manner, the scientists sentation in Amygdala and Prefrontal a postdoc in Murray’s lab. “The anatomy found that fewer neurons in the ante- Cortex.” Annual Review of Neuro- OTH: WR. JENISON

B suggests that it’s the amygdala telling rior cingulate cortex changed their firing science 2010.

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