About two months before he sat wild-haired, bug-eyed and dazed as a judge told him he faced murder charges, James Eagan Holmes was supposed to give a presentation on a topic so complex that most people would barely understand its title.

Near the same time he would have been discussing “microRNA biomarkers” with doctoral students and faculty, authorities say, Holmes began amassing the cache of guns and ammunition he used to carry out one of the worst mass shootings in U.S. history.

University of Colorado Denver officials won’t say whether he gave that presentation, listed on the syllabus for a class called “biological basis of psychiatric and neurological disorders.” In any case, Holmes was by then already slipping out of the rarefied world of intellect and scientific discovery that for much of his 24 years had seemed embedded in his DNA.

Holmes took an oral examination June 7 and dropped out of the elite CU Denver neuroscience graduate program June 10.

He is now accused of murder and attempted murder in the deaths of 12 people and the injuring of another 58 during a midnight premiere of “The Dark Knight Rises” on July 20 at an Aurora movie theater.

“Aspiring scientist”

In Holmes’ 2010 résumé, he calls himself an “aspiring scientist.” The student experience he listed then, as he applied for lab-technician jobs online, is an impressive catalog of research in neuroscience: the study of the brain and nervous system.

Digitization of mouse muscle. Neuronal mapping of the zebra finch. Dissection, staining and photography of hummingbird flight muscles.

As a lab assistant at the University of California, Riverside, Holmes picked up skills such as dissecting cells and using dye to stain biological tissues before examining them under a microscope, according to the résumé.

No one at CU Denver and few in the broader neuroscience community would talk about Holmes directly. But directors of CU’s neuroscience graduate program described the environment Holmes had entered, and was withdrawing from, as intellectually demanding and rewarding.

Every year, 100 or so budding scientists apply to the CU Denver doctoral program in neuroscience. Ultimately, only about six are admitted, said program director Angie Ribera.

In 2011, Holmes was one of the six.

Then Holmes was chosen for inclusion in a National Institutes of Health grant program designed to train the best and brightest for careers as neuroscience researchers.

Each year, Diego Restrepo, co-director of CU Denver’s NeuroScience Center, and a group of faculty select three of the most promising first-year doctoral students and three second-year students to split the grant.

It covers tuition and fees, and provides a stipend for living expenses, in part because the rigorous neuroscience program hardly leaves time for students to work.

The NIH awards the grant, in Restrepo’s name, to the university. The intent of the grant is not to support any particular research but to train future neuroscientists, Restrepo said.

How the brain works

Neuroscience is a relatively new discipline, becoming more attractive to doctoral students over the past decade or so because of the intrigue of the as-yet unexplained. It is the study of how nerve cells communicate with one another, and how the brain generates thoughts and ideas, controls movement and processes vision, smell and hearing.

“One of the great mysteries is how our brain works,” said Dr. James Ashe, director of the graduate program in neuroscience at the University of Minnesota. “We have a fair idea how the kidney works; we know a lot about the heart. There are far more unknown areas in brain research than in many fields.”

Some who earn doctorate degrees in neuroscience go on to run their own research labs, either at a university or in the pharmaceutical or biotech industries. Others end up teaching or going to medical school, Ashe said.

Their work is complex, to say the least. Ashe, for example, is trying to help people with prosthetic limbs. The goal is to implant an electrode in a person’s brain that would collect signals that tell an arm or leg to move. The signals would be interpreted by a mini-computer and broadcast to another device that would understand the signal and tell the prosthetic what to do.

At CU Denver, first-year doctoral students take courses that include cellular and molecular neurobiology and biomedical core courses, Ribera said. Most of the roughly six years it takes to earn that Ph.D., though, are spent working — sometimes night and day — in a lab.

First-year students, such as Holmes, rotate through three labs, working with a different researcher in each for 12 weeks.

At the end of that first year — the program continues almost year-round — “the student sits down with three faculty members, for 45 minutes to an hour. The three faculty members represent the three courses,” Ribera said.

The goal is not to pass or fail the student, or even to grade them.

“It’s an oral exam — a discussion, really,” she said. That discussion includes a student’s research strengths and weaknesses.

The students’ work is scrutinized not to see whether they made any scientific discoveries but to make sure they are on the right track to understanding how to design research that will lead them to answer the scientific question they are asking, Ribera said.

By the time they are ready to defend their doctoral dissertation, students are expected to have their research published in a peer-reviewed journal, Ribera said.

It’s a rigorous, demanding program.

“But if this is what you want to do, if it’s your passion,” the load isn’t crushing, Ribera said.

Of those admitted, nearly 90 percent will earn their Ph.D., she said.

Federal stipends, common at neuroscience graduate programs across the country, allow students to devote their time to coursework and lab work, Ashe said.

“It’s very unusual for students in our program or most other neuroscience programs to have jobs,” he said. “It’s unrealistic.”

In Minnesota, first-year students typically spend up to 60 hours a week on coursework, in class and in lab rotation. Competition among the chosen few in the program — at Minnesota, that’s about nine to 12 students each year — can become an issue if students are vying for lab spots with a particularly popular faculty researcher.

Quiet and reserved

By many accounts, Holmes would have appeared to be an excellent candidate for a doctoral program.

People in the comfortable San Diego suburb where Holmes grew up have described him as quiet and reserved back then. A classmate from Westview High School told The New York Times that Holmes played soccer and ran track for a while but gave up those sports to devote himself to academics.

Holmes won merit scholarships to the University of California, Riverside and graduated in 2010 as an honors student in neuroscience, school officials said.

At UC-Riverside, Holmes “was at the top of the top,” Chancellor Timothy White said at a news conference after the shootings. “He really distinguished himself.”

The world of neuroscience research is small enough that some resented its recent link to an accused mass murderer and declined to comment for this story.

“The neuroscience community, like all of the public, is deeply saddened by the tragedy that occurred in Aurora, and (I) am sorry to say that we can’t do an interview at this time,” Todd Bent-sen, director of public information and outreach at the Society for Neuroscience, said in an e-mail.

Karen Augé: 303-954-1733, kauge@denverpost.com or twitter.com/karenauge

Jennifer Brown: 303-954-1593, jbrown@denverpost.com or twitter.com/jbrowndpost