Nonassociative learning as gated neural integrator and differentiator in stimulus-response pathways http://www.behavioralandbrainfunctions.com/content/pdf/1744-9081-2-29.pdf Synopsis What could drug addiction, the phantom pain experienced by amputees, and a life-threatening respiratory condition called apneustic breathing have in common? A new theory published in the online open-access journal Behavioral and Brain Functions suggests that they all may be signs of brain calculus and brain logic computations gone haywire. So says the paper’s lead author Dr. Chi-Sang Poon, a scientist at the Harvard University-Massachusetts Institute of Technology Division of Health Sciences and Technology. According to Poon, our brain is constantly bombarded with vast amounts of sensory information that must be continuously sorted into actionable and nonactionable items in order to prioritize. Such a complex mental task involves sophisticated mathematical calculations like integral-differential calculus and Boolean logic operations, which are basic to any decision-making process. But unlike the number crunching on digital computers, the new theory proposes that our brain may be doing the math automatically by using built-in neural circuitries capable of learning on the spot. Such behavioral learning has long been thought to be a “dual process,” as exemplified by the everyday experience of habituation to prolonged exposure to fragrance and sensitization to recurrent shock and pain. Dr. Eric Kandel’s pioneering work at Columbia University in the 1970s on neural circuitries for habituation and sensitization in the sea slug Aplysia resulted in a Nobel Prize in Physiology or Medicine in 2000 – but is such quotidian behavioral learning really important to one’s well-being? Then earlier in 2000, Poon’s research group discovered that the mammalian brain displayed yet another mode of behavioral learning that had confounded previous studies. They called this new behavior “desensitization,” in contrast to sensitization and habituation. Their research demonstrated that desensitization and habituation had similar “differentiator” effects on the stimulus-response relationship, much like a “high-pass filter” in an audio system. However, habituation was found to be turned on or off by the stimulus itself, much like a Boolean toggle switch. Similarly, the effects of sensitization were shown to be analogous to those of an “integrator” or “low-pass filter,” with or without the Boolean on-off switching. These pivotal discoveries provided the pieces to the puzzle that inspired Poon’s current theory in which habituation, sensitization, and desensitization are the basic machinery for online calculus and logic computations in the brain. The theory seems to bring these different concepts together. In effect, behavioral learning is a form of brain intelligence whereby integral-differential calculus and on-off Boolean logics are used to filter incoming sensory signals in order to determine continuously what needs attention and what doesn’t – which is our brain’s way of telling “what’s hot and what’s not”. This so-called “sensory firewall” allows the brain to relax and to economize its activities until warning bells ring. It can also provide a fail-safe compensation when sensory cues are distorted. A mistuning of the habituation or sensitization components in the firewall could leave an individual either numbly insensitive, as in “hearing without listening,” or excessively sensory defensive, as in hysteria. Alternately, a breakdown of the desensitization component could produce a sensory delusion. The effects of desensitization were discovered by Poon’s team while studying the classic Hering-Breuer respiratory reflex. Here, the inspiratory drive is slaked once the vagus nerves sense the lungs are inflated. (Try it yourself by taking a deep breath and holding it. Momentarily, you will feel like you want to exhale instead of inhale). This simple reflex triggers inspiratory-to-expiratory phase switching, which is essential for maintaining a cyclical respiratory rhythm. Poon’s group discovered that, in animals whose vagus nerves are severed, a specific brainstem region in the pons that is normally desensitized would steer the respiratory rhythm in place of the vagus nerves. The pons seemed to act as a “phantom” or surrogate for the vagus nerves – much like the phantom pain sensation experienced by amputees. However, in this case, the compensatory action provided an important respiratory fail-safe mechanism crucial for survival. Indeed, classical experiments have shown that when both the vagus nerves and the pons malfunction, an animal goes into an inhalation-only mode, desperately trying to distend its lungs. This results in a life-threatening neurological state called apneustic breathing. Poon and colleagues believe this inspiratory-craving state is functionally similar to obsessive or addictive behaviors, which may result when craving-inhibiting pathways in reward-related brain regions are desensitized. If so, response desensitization could be a new pattern for brain intelligence, and any resulting errors in individual sensory systems may produce abnormalities ranging from phantom pain to addictive behavior. In recent years, neuroscientists have been increasingly intrigued by the idea that the human mind might be connected with the body’s environment through the construction of certain internal models. This was hinted by the seventeenth-century French philosopher and mathematician René Descartes. If Poon and colleagues are correct, the sensory firewall mediated by nonassociative learning may be the gatekeeper of the internal models that govern sensory integration in the brain.