(Image caption: In this image, marking shows the axons in retinal neurons (in red) that innervate the superior colliculus (in blue) in a “normal” mouse. Credit: © Michael Reber / Institut des Neurosciences Cellulaires et Intégratives)

Confirmation of the neurobiological origin of attention-deficit disorder

A study, carried out on mice, has just confirmed the neurobiological origin of attention-deficit disorder (ADD), a syndrome whose causes are poorly understood. Researchers from CNRS, the University of Strasbourg and INSERM1 have identified a cerebral structure, the superior colliculus, where hyperstimulation causes behavior modifications similar to those of some patients who suffer from ADD. Their work also shows noradrenaline accumulation in the affected area, shedding light on this chemical mediator having a role in attention disorders. These results are published in the journal Brain Structure and Function.

Attention-deficit disorder affects between 4-8% of children. It manifests mainly through disturbed attention and verbal and motor impulsiveness, sometimes accompanied by hyperactivity. About 60% of these children still show symptoms in adulthood. No cure exists at this time. The only effective treatment is to administer psychostimulants, but these have substantial side effects, such as dependence. Persistent controversy surrounding the neurobiological origin of this disorder has hindered the development of new treatments.

The study in Strasbourg investigated the behavior of transgenic mice having developmental defects in the superior colliculus. This structure, located in the midbrain, is a sensory hub involved in controlling attention and visual and spatial orientation. The mice studied were characterized by duplicated neuron projections between the superior colliculus and the retina. This anomaly causes visual hyperstimulation and excess noradrenaline in the superior colliculus. The effects of the neurotransmitter noradrenaline, which vary from species to species, are still poorly understood. However, we do know that this noradrenaline imbalance is associated with significant behavioral changes in mice carrying the genetic mutation. By studying them, researchers have observed a loss of inhibition: for example mice hesitate less to penetrate a hostile environment. They have difficulties in understanding relevant information and demonstrate a form of impulsiveness. These symptoms remind us of adult patients suffering from one of the forms of ADD.

Currently, the fundamental work on ADD uses mainly animal models obtained by mutations that disturb dopamine production and transmission pathways. In mice with a malformed superior colliculus, these pathways are intact. The changes occur elsewhere in the neural networks of the midbrain. By broadening the classic boundary used to research its causes, using these new models would allow a more global approach to ADD to be developed. Characterizing the effects of noradrenaline on the superior colliculus more precisely could open the way to innovative therapeutic strategies.

How Vision Captures Sound Now Somewhat Uncertain

When listening to someone speak, we also rely on lip-reading and gestures to help us understand what the person is saying.

To link these sights and sounds, the brain has to know where each stimulus is located so it can coordinate processing of related visual and auditory aspects of the scene. That’s how we can single out a conversation when it’s one of many going on in a room.

While past research has shown that the brain creates a similar code for vision and hearing to integrate this information, Duke University researchers have found the opposite: neurons in a particular brain region respond differently, not similarly, based on whether the stimuli is visual or auditory.

The finding, which posted Jan. 15 in the journal PLOS ONE, provides insight into how vision captures the location of perceived sound.

The idea among brain researchers has been that the neurons in a brain area known as the superior colliculus employ a “zone defense” when signaling where stimuli are located. That is, each neuron monitors a particular region of an external scene and responds whenever a stimulus — either visual or auditory — appears in that location. Through teamwork, the ensemble of neurons provides coverage of the entire scene.

But the study by Duke researchers found that auditory neurons don’t behave that way. When the target was a sound, the neurons responded as if playing a game of tug-of-war, said lead author Jennifer Groh, a professor of psychology and neuroscience at Duke.   

"The neurons responded to nearly all sound locations. But how vigorously they responded depended on where the sound was," Groh said. "It’s still teamwork, but a different kind. It’s pretty cool that the neurons can use two different strategies, play two different games, at the same time."

Groh said the finding opens up a mystery: if neurons respond differently to visual and auditory stimuli at similar locations in space, then the underlying mechanism of how vision captures sound is now somewhat uncertain.

"Which neurons are ‘on’ tells you where a visual stimulus is located, but how strongly they’re ‘on’ tells you where an auditory stimulus is located," said Groh, who conducted the study with co-author Jung Ah Lee, a postdoctoral fellow at Duke.

"Both of these kinds of signals can be used to control behavior, like eye movements, but it is trickier to envision how one type of signal might directly influence the other." 

The study involved assessing the responses of neurons, located in the rostral superior colliculus of the midbrain, as two rhesus monkeys moved their eyes to visual and auditory targets.

The sensory targets — light-emitting diodes attached to the front of nine speakers — were placed 58 inches in front of the animals. The speakers were located from 24 degrees left to 24 degrees right of the monkey in 6-degree increments.  

The researchers then measured the monkey’s responses to bursts of white noise and the illuminating of the lights.

Groh said how the brain takes raw input of one form and converts it into something else “may be broadly useful for more cognitive processes.”

"As we develop a better understanding of how those computations unfold it may help us understand a little bit more about how we think," she said.