Born and raised in St. Louis, Kusama has retained the flat vowels and the “cheerful morbidity” of a Midwesterner. She likes to joke that her grandmother would take the kids to the local cemetery to remind them of “you know, little Bobby Jones — he was decapitated in a freak accident.” Kusama’s father immigrated from Japan to attend medical school at Washington University, and her mother is of Scottish-Irish descent. She was an occupational therapist, and he was a child psychiatrist who came home with the occasional vivid tale of suffering.

There were very few nonwhite children in Kusama’s school, and the family did not go to church, making them doubly outcast. Kusama, whose fashion ran to plaid jodhpurs and sparkly socks, discovered that she had a seizure disorder when, during a seventh-grade health lesson about drunken driving, she projectile-vomited. She was seated directly behind a student with long hair. “It’s that kind of thing where you’re just like, I’m now a marked kid,” she remembers. “And it was a lonely time.” But something about that isolation was emboldening. “I’d rather endure solitude than have pretend intimacy,” she says. Her family was reserved about emotions; watching movies helped her feel seen.

For college, she enrolled at New York University’s Tisch School of the Arts, where her first student films were stylized and arty. One of her professors, Carol Dysinger, remembers shots of a woman sitting on a chair in an empty swimming pool and an egg displayed against a velvet background. After Dysinger encouraged Kusama to “put her heart onscreen,” her next short consisted of shots of young people riding the subway or sitting in windows while she talked in voice-over about her friends and her worries about them. It blew Dysinger away. Kusama was starting to find her way of storytelling: a visual style that was poetic and simple — almost tough in its simplicity — paired with a plain, direct investigation of feeling. At N.Y.U., Kusama also found a tight group of friends and creative collaborators. Then, during senior year, the group was shattered when her writing partner mixed cocaine and heroin and died.

After graduation, Kusama tried to finish the script they had been writing together, but it went nowhere. To make ends meet, she did odd jobs, including babysitting, editing student films and rolling loose change for a friend of Dysinger’s. All around her, people were dying — of drugs, of AIDS. “It was a time of extreme impermanence,” she told me. She became an assistant to Sayles and the producer Maggie Renzi, both of whom she impressed with her unflappability. (“Somebody from the Weinstein Company called and said, ‘You know, I’m going to lose my job unless I can get John on the phone with Bob Weinstein today,’ ” Sayles recalls. “She basically said, ‘I feel so bad for you that you have a job like that and that your life has come to such a pass.’ ”) She started boxing at Gleason’s Gym in Dumbo, where she was one of only a few women, and she began noticing young women on the subway who looked as angry as she felt. It occurred to her that she could tell their stories. After Dysinger bet her a hundred dollars that she couldn’t finish a script in a month, she wrote what would eventually become “Girlfight.”

Two years after her friend died, Kusama and her sister, Kristen, were together in the Fort Greene house they shared with friends when they got the call that their brother, Kevin, had died of a heroin overdose. Kevin had been charismatic and intelligent but also, in Kusama’s description, “a kid who came out screaming and kind of didn’t stop — it was his nature,” she says, “to be in conflict with life itself.” When they were young, his saucer sled flew out onto the ice, and he walked out to retrieve it; a bunch of kids were playing ice hockey in the center of the frozen pond, and it looked safe. But he fell through the ice. “That was his life,” she says. “He was touched by that kind of closeness to catastrophe.”

Everything changed after these deaths. Kusama didn’t know how to understand the world, so how could she make a movie about it? There was also the matter of being, or becoming, an adult. “It really did hit me in my 20s: I’m not going to make a good movie if I don’t know how to pay my rent,” she says. “That was the hammer on my head, realizing that I can’t make a movie if I can’t take care of myself.”