Distinct mental states can be distinguished using a form of functional magnetic resonance imaging (fMRI) to detect unique patterns of activity in coordinated "networks" within the brain. The technique, developed by researchers at Stanford University School of Medicine, may lead to novel diagnostic tests for Alzheimer's disease and other brain disorders in which network function is disrupted. In a novel set of experiments, researchers led by Michael Greicius, assistant professor of neurology and neurological sciences, determined from brain-imaging data whether experimental subjects were recalling events of the day, singing silently to themselves, performing mental arithmetic or merely relaxing. In the study, subjects engaged in these mental activities at their own natural pace, rather than in a controlled, precisely timed fashion as is typically required in experiments involving fMRI. This suggests that the new method — a variation on fMRI — could help scientists learn more about what the brain is doing during the free-flowing mental states through which individuals move, minute-to-minute, in the real world. Functional MRI can pinpoint active brain regions in which nerve cells are firing rapidly. In standard fMRI studies, subjects perform assigned mental tasks on cue in a highly controlled environment. The researcher typically divides the scan into task periods and non-task periods with strict start and stop points for each. Researchers can detect brain regions activated by the task by subtracting signals obtained during non-task periods from those obtained during the task. To identify which part of the brain is involved in, for example, a memory task, traditional fMRI studies require experimenters to control the timing of each recalled event. "With standard fMRI, you need to know just when your subjects start focusing on a mental task and just when they stop," Greicius said. "But that isn't how real people in the day-to-day world think." In their analysis, the Stanford team broke free of this scripted approach by looking not for brain regions that showed heightened activity during one mental state versus another, but for coordinated activity between brain regions, defining distinct brain states. This let subjects think in a self-paced manner more closely resembling the way they think in the world outside the MRI scanner. Instead of breaking up a cognitive state into short blocks of task and non-task, the researchers used uninterrupted scan periods ranging from 30 s to 10 min, allowing subjects to follow their own thought cues at their own pace. The team captured subjects' mental states even when the duration of the scans was reduced to as little as 1 min or less — all the more reflective of real-world cognition. Greicius is senior author of the new study, which was published online May 26 in Cerebral Cortex. For more information, visit: www.stanford.edu