There are parts of the United States where the Interstate Highway System does not go. This concept is somewhat foreign here on the East Coast, where the IHS is spun as tightly as a spider web and sprinkled with urban hubs. It's hard to plan a journey of a few hundred miles in the Eastern U.S. without traveling on an Interstate. If you play this game (people do), you'll find that the longest routes that don't involve our biggest highways are all in the West, where the system looks more like a soccer net, leaving wide swaths of land untouched. Somewhere in one of these dead zones of the world's biggest public works project lies, at least by one measure, the most isolated town in the United States.
By all accounts, this distinction is not particularly meaningful. Interstates are not anti-isolation machines: there are big cities without Interstate Highways, like Fresno, California, and Brownsville, Texas, and there are stretches of Interstate with no humans in sight. There are a number of more statistically rigorous ways to calculate isolation. Some of these are fun: Gorda, California, on the cliff-hugging curves of Route 1, is legendary for having the highest gas prices in the country.