Recently, there has been major progress in identifying brain systems associated with complex behavioral and mental functions. We believe that this work is relevant to clinical psychiatry because abnormalities occurring in specific brain systems are responsible for psychiatric symptoms and disorders. In this post, we will first describe what we mean by functional brain systems, and then we will discuss how a common illness - Alzheimer's disease - is likely to involve the breakdown of a brain system called the "default network."

The National Institutes of Health have recently made the mapping of functional brain systems a high priority by sponsoring a large research endeavor called the "Human Brain Connectome Project." In this initiative, scientists will use state-of-the-art methods to understand how various regions of the human brain work together to perform specific functions. In other words, these scientists will be studying the functional connectivity of the human brain.

So, what is functional connectivity? It is the way that various regions of the brain are connected and work together as integrated systems to accomplish specific functions, including the complex processing involved in cognition, emotion, and motivation, the so-called "mental trilogy." The ability to identify specific functional brain systems has been aided greatly by the development of new brain imaging techniques, including functional magnetic resonance imaging (fMRI). fMRI is capable of measuring the functional activity of brain regions during rest as well as during specific tasks. Functional connectivity imaging examines the correlations and interdependencies among brain regions as they interact with each other to do specific tasks.

We already know that the human brain is organized into functional systems that are referred to as "intrinsic connectivity networks." These "ICNs" help humans process cognitive, emotional, and motivational information. One such functional brain system is called the "default network." The default network consists of a group of brain regions that communicate and share information during those periods of time when we are not paying attention to specific tasks, i.e., when we are daydreaming or resting. It turns out that during these times when we are not actively engaged in specific tasks, our brains are hard at work assessing our internal state, processing our memories, and contemplating future endeavors. In effect, the default network helps us "think" and "plan." The default system is critical for information processing and uses a lot of the brain's energy.

When something happens that requires us to focus our attention, the brain shifts out of default mode and activates a different set of brain networks (ICNs) that regulate attention. Specific regions of the frontal and parietal lobes of the brain become active in a coordinated manner and help us to turn our attention toward the new tasks. In fact, one ICN helps us shift our attention, and a different ICN helps us stay focused on the tasks at hand.

It is likely that neurologic and psychiatric illnesses will eventually be understood by defining the specific malfunctions of ICNs that are devoted to specific tasks. For example, recent research suggests that the key brain regions involved in the default network are the same brain regions that show the earliest destructive changes in Alzheimer's disease and some changes in the connectivity of the default system appear to occur before the onset of clinical symptoms. Why? Although there is a lot of speculation, we really don't know. The high energy use of the default system may be at least one contributing factor. Figuring out why may lead to new treatment approaches.

Another interesting example where breakdown in a specific ICN appears to be involved in a specific disorder is the rare but fascinating neuropsychiatric illness called "behavioral variant frontotemporal dementia." This illness typically begins in late middle age (in the 50s or early 60s). Early symptoms include markedly inappropriate social behaviors. For example, a generally reserved individual might gradually develop dramatic, disinhibited behavior, such as telling loud and embarrassing stories at a restaurant or making fun of a person at the table next to him. Over time, changes involving speech, memory, and independent function eventually occur, and the illness progresses to a clinical state that resembles advanced Alzheimer's disease.

Recent research suggests that behavioral variant frontotemporal dementia involves loss of brain cells in a functional brain system called the "emotional salience network." This ICN involves several areas of the brain's limbic system. (The limbic system is involved in processing emotional information.) Perhaps, this emotional salience system helps us be appropriate in our social interactions and lets us integrate emotional components into the way we process information. Why this system breaks down in this rare form of dementia remains a mystery.

As functional brain systems are better characterized, researchers should be able to examine which systems are malfunctioning in illnesses like schizophrenia, bipolar disorder, and autism. The more we learn, the more we will be able to define the processing defects associated with these disorders and develop better treatments.

The recent explosion of information utilizing imaging procedures to describe brain systems is but one of many exciting approaches that will add to our abilities to understand psychiatric symptoms and help people suffering from these severe, disabling illnesses.

This posting was co-written by Charles Zorumski, MD and Eugene Rubin MD, PhD. Neither of us have any financial conflicts of interests with the pharmaceutical industry or industries involved in the development of new devices.

About the Authors

Charles F. Zorumski, MD

Charles F. Zorumski, MD, is Samuel B. Guze Professor and Head of Psychiatry at Washington University in St. Louis - School of Medicine.

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