Why do we do the things that we do? Why do we some­times choose to be lov­ing par­ents and oth­er times engage in irra­tional self-destructive behav­iors? What dri­ves us to some­times be altru­is­tic and oth­er times make deci­sions that real­ly threat­en our very sur­vival? Well, the answer lies in our brains. Our brains evolved to ensure that we repeat behav­iors that will lead to our sur­vival. There are mech­a­nisms in the brain that tell us that food tastes good when we’re hun­gry, water tastes great when we’re thirsty, and sex is pret­ty good most of the time. 

Work in my lab and oth­er Stanford University neu­ro­science labs is using pret­ty advanced, inno­v­a­tive method­ol­o­gy such as the injec­tion of genetically-modified virus­es into ani­mal brains, and nov­el brain imag­ing tech­niques in human sub­jects to advance our under­stand­ing of the mech­a­nisms that allow us to feel joy, allow us to feel aver­sion or pain, and how these influ­ence the deci­sions we make.

These mech­a­nisms are not only impor­tant for the behav­iors that lead to our sur­vival, but also for exam­ple the finan­cial deci­sions we make, and the deci­sions we make as soci­eties. They’re also impor­tant for under­stand­ing the patho­phys­i­ol­o­gy of brain dis­or­ders such as addic­tion and depression.

Not sur­pris­ing­ly, these mech­a­nisms are not sim­ple. The very same stim­u­lus can change from being high­ly reward­ing to high­ly aver­sive in a mat­ter of sec­onds. Any of you who have been in an inti­mate rela­tion­ship I think know exact­ly what I’m talk­ing about. 

The first clue that there were spe­cif­ic inter­con­nect­ed brain areas that gen­er­ate reward in our brains came from clas­sic exper­i­ments in the 1950s, where it was found that rats would press a bar for hours a day to receive elec­tri­cal stim­u­la­tion in spe­cif­ic parts of their brain. We know the brain uses a large num­ber of chem­i­cal mes­sen­gers to sub­serve its func­tions. Key parts of the reward cir­cuit­ry use a very spe­cial chem­i­cal mes­sen­ger named dopamine.

But dopamine does not mag­i­cal­ly work in a vac­u­um. It’s made by spe­cif­ic cells in the brain. These cells are found at the base of the brain in a part of the brain called the ven­tral tegmen­tal area. These cells in the ven­tral tegmen­tal area that make dopamine com­mu­ni­cate with oth­er parts of the brain, the most impor­tant part of the brain being the nucle­us accum­bens, which is found in the mid­dle of the brain and is very impor­tant for trans­lat­ing our moti­va­tions into action.

We know both in ani­mal brains and human brains that dopamine in the nucle­us accum­bens is released in response to food, in response to sex. It’s very pow­er­ful­ly released in response to drugs of abuse. And as this human brain scan shows us, the nucle­us accum­bens is acti­vat­ed in the human brain even in response to stim­uli such as mon­e­tary rewards.

Work in my lab, how­ev­er, has revealed that the reward cir­cuit­ry is much more com­pli­cat­ed than we pre­vi­ous­ly envi­sioned. It’s much more like the London Underground. It con­sists of a num­ber of key inter­con­nect­ed hubs or nodes, and the com­mu­ni­ca­tion between these nodes is what’s impor­tant for gen­er­at­ing our feel­ings of reward or aversion.

We also know that the reward cir­cuit­ry is not sta­t­ic, it’s not fixed. It responds to expe­ri­ence. For exam­ple, addic­tive sub­stances mod­i­fy the reward cir­cuit­ry in a patho­log­i­cal way, and this is what leads to drug addic­tion. Similarly, the reward cir­cuit­ry mal­func­tions dur­ing depres­sion, so you no longer can expe­ri­ence the joys of life. In fact in autism, which affects one to two per­cent of the world’s chil­dren, we believe that the inabil­i­ty to expe­ri­ence the nor­mal joy or plea­sure of social inter­ac­tions may be due to the fact that oth­er spe­cial chem­i­cal mes­sen­gers by the names of oxy­tocin and sero­tonin don’t mod­u­late the cir­cuit­ry in a nor­mal fashion.

By elu­ci­dat­ing the detailed mol­e­c­u­lar changes that occur in this cir­cuit­ry dur­ing brain dis­or­ders such as addic­tion and depres­sion and autism, we’re going to be able to make much more spe­cif­ic and effi­ca­cious treat­ments for these high­ly preva­lent dis­or­ders that sap the nor­mal joys of life.

Robert Malenka Mechanism Risk Reward 00 05 05

I’m par­tic­u­lar­ly excit­ed about some of the inno­va­tions and new method­olo­gies we’re devel­op­ing at Stanford. Methods such as the expres­sion of light-sensitive pro­teins in ani­mal brains, and the appli­ca­tion of trans­mag­net­ic stim­u­la­tion in human brains. Using these method­olo­gies, we’re going to be able to advance our under­stand­ing of the neur­al mech­a­nisms under­ly­ing adap­tive and patho­log­i­cal deci­sion mak­ing, with the long term goal of reduc­ing and hope­ful­ly even elim­i­nat­ing societally-destructive deci­sions, and pro­mot­ing those deci­sions that will allow our plan­et’s inhab­i­tants to lead healthy, pro­duc­tive and ulti­mate­ly highly-rewarding lives. 

My ques­tion is kind of sim­ple. Do you believe any­thing I just told you? That is, you know, I’m a neu­ro­sci­en­tist and also a psy­chi­a­trist. And I got into this field because I pas­sion­ate­ly believe that the brain is what medi­ates our feel­ings, our thoughts, and behav­iors. And I do believe that by under­stand­ing the mech­a­nisms that cause these expe­ri­ences and make us make good deci­sions but often very bad deci­sions, that we will be able to not only cure dis­eases, but we will improve soci­ety, and I think we des­per­ate­ly need to. So I’ll stop there. 

Thank you.

Further Reference

Robert Malenka faculty profile at Stanford Medicine.