Alzheimer Research Series on the Default Network

Abstract

The idea of the default mode network, an interconnected set of brain regions that are active when the brain is resting and that power down during focused mental tasks, was first proposed in 2001, but it quickly became a hot topic in cognitive neuroscience and for Alzheimer’s disease (AD) researchers. The seesaw activation and deactivation of the default network and task-related brain regions appears critical for peak performance on memory tasks and deactivation and network connectivity are disrupted early in AD, perhaps as a result of amyloid deposition [1]. AD is not the only disease where network activity suffers. A new study in PNAS reveals that function of the default network, as measured by fMRI, is also altered in people with schizophrenia, and their healthy first-degree relatives [2]. The changes are somewhat different from those seen in AD – network connectivity is strengthened, for one, and overall network activity is increased both at rest and during task. The study, from Susan Whitfield-Gabrieli at MIT, suggests that changes in default mode activity and alterations in the normal balance between activation and deactivation contribute to the symptoms of schizophrenia, and could be part of the genetic risk for the disease. To look at the default network in people with schizophrenia, the researchers performed fMRI scans on subjects while they were idle, and then when they engaged in a simple memory test. That allowed assessment of the basal network activity, and the extent of deactivation that occurred during a task that required concentration. The study compared 13 volunteers with early phase schizophrenia, 13 unaffected first-degree relatives and 13 healthy controls. When subjects performed the test, suppression of the default mode network was most effective in controls, and decreased in both patients and relatives. Overall, the deactivation in the default network and activation of task-related areas were strongly correlated in control subjects, but the seesaw effect was much weaker in patients and relatives. The result was a consistent hyperactivity of the default network. In addition, the patients and relatives showed stronger connectively between the medial prefrontal cortex and the precuneous and the rest of the default network, whether measured at rest or during a task. The strength of connectivity and defect in deactivation correlated with poorer performance in the working memory task and stronger schizophrenia symptoms, suggesting that the default mode network could play an important role in the cognitive and clinical symptoms of schizophrenia. In addition, the observation that unaffected relatives show similar changes suggests that aberrant network activity stems from genetic risk and is causal, rather than just a consequence of the disease, Whitfield-Gabrieli told ARF. “In the future, it may be possible to use these fMRI measures as a way of diagnosing disease, or to figure out how patients are responding to treatment,” she said. In terms of the symptoms of schizophrenia, it is interesting that the default mode network is activated during internal, self-referential thought. Network overactivity could lead to problems integrating the internal and external worlds, the authors speculate. Besides AD and schizophrenia, other diseases where default mode network activity is known to be altered include autism,