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Researchers from Case Western Reserve University School of Medicine and colleagues have discovered how two brain regions united to maintain attention, and how discordance between the regions could cause attention deficit disorders, including schizophrenia, bipolar disorder and depression. People with attention deficits have difficulty focusing and often display compulsive behavior.
Attention deficit disorders are due to dysfunction in a gene-ErbB4 that helps different brain regions to communicate. ErbB4 is a risk factor for psychiatric disorders, and is required to maintain healthy neurotransmitter levels in the brain. Lacking ErbB4 activity in specific brain regions leads to poor performance on timed attention tasks. Neuroscientists describe the kind of thought-driven attention required for the tasks as “top-down attention.”
Top-down attention is goal-oriented, and related to focus. Those who lack efficient top-down attention are at a higher risk for attention deficit hyperactivity disorder ADHD. ErbB4 is a risk factor for schizophrenia, bipolar disorder, and major depression, the results provide insights into mechanisms of these disorders. When the researchers attached probes to the mice to measure brain activity, they found mice without ErbB4 had brain regions that were acting independently, rather than together in synchrony.
The researchers studied the prefrontal cortex which is associated with decision-making and the hippocampus that supports memory. These two regions coordinate for a variety of brain tasks, including memory and attention. They discovered top-down attention, previously thought to be controlled by the prefrontal cortex, also involves the hippocampus in a manner where the two regions are highly synchronized when attention is high. The findings give importance to synchrony between the prefrontal cortex and hippocampus in top-down attention and open up the possibility that attention deficit disorders, like ADHD, might involve impairments in the synchrony between these two regions.
ErbB4 coordinates a cascade of brain signals that “bridge” the two regions, it encodes a receptor on the surface of brain cells. When a protein (neuregulin-1) attaches to the ErbB4 receptor, it triggers a chain reaction that determines neurotransmitter levels in the prefrontal cortex and hippocampus. Without ErbB4, neurotransmitter levels go awry.
The researchers discovered mice lacking ErbB4 have low levels of neurotransmitter—GABA, or gamma-aminobutyric acid—in their brain. Low GABA levels can lead to impaired top-down attention in the prefrontal cortex, and impairs how the prefrontal cortex can efficiently coordinate with the hippocampus. ErbB4 links the two brain regions to maintain attention.
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