It’s called mental imbalance for a reason. Sanity hangs, in part, in the gentle balance of chemicals strung together within regions of the brain in an intricate matrix.
In schizophrenia, the matrix is sharply jarred, debilitating the mind and triggering hallucinations. Now, researchers at the Georgia Institute of Technology have created an interactive model of that matrix to fast-track research and treatment of the tormenting disorder.
It uses massive amounts of research data to simulate major systemic chemical changes in the brains of schizophrenia sufferers but depicts them in simple, colorful graphics.
Clinicians could use it to help patients and their loved ones better understand the chemical underpinnings of the disease and therapeutic alternatives. And researchers could test out hypotheses virtually, quickly and easily, and get a better overall sense of the disease.
Qi and his team built the computational model around the neurochemistry behind that cognitive function, which goes badly awry in schizophrenia.
Working memory is short-term recollection that lends the mind coherence. It remembers what we saw, said or did seconds ago and what we want to do seconds from now.
Hallucinations may be the eye-catching, popularized symptom of schizophrenia, but the disease’s impairment of working memory, though less attention-grabbing, arguably debilitates sufferers more.
“Working memory deficits disrupt storing and processing of information as basic as letters and numbers, and they hinder the recall of stored information,” Qi said. “That makes learning and planning difficult.”
Sorry, no drugs
The researchers found that there is a stark lack of medical treatment for this symptom.
“Cognitive symptoms were actually associated with schizophrenia before symptoms like hallucinations became the focus,” said Eberhard Voit, a Georgia Tech biomedical engineer and a Georgia Research Alliance eminent scholar, who supervised the modeling effort. “Yet, drugs for schizophrenia mainly target the latter symptoms.”
Two neurotransmitters, glutamate and gamma-aminobutyric acid (GABA) are crucial to working memory in their coordination of two brain regions, the dorsal prefrontal cortex and the basal ganglia.
Glutamate boosts nerve transmission, and GABA tones it down, and it’s important for the two to strike a balance. But other neurotransmitters associated with additional brain regions also tug at that balance.
Mining disparate data
The Georgia Tech researchers collected studies on brain chemistry in schizophrenia from nearly 50 labs around the world, and mined the data.
To interpret them, they consulted researchers who have dedicated their lives to exploring schizophrenia and they fed the information into differential equations representing relationships between neurochemical systems.
They arrived at a novel map of the brain chemistry behind working memory dysfunction in schizophrenia. “That is new, this map. It reflects the collective knowledge of the scientific community,” Voit said.
“With the information assembled, we wrote code to implement this model,” Qi said. The result is a program of the neurochemical matrix that’s easy to use.
Playing with mobiles
Users can input varying levels of neurotransmitters, and the matrix model simulates the labyrinthine domino effects they have on each other. But the output to the user is much simpler, even playful.
“What the user sees is a mobile tilting back and forth,” Voit said. Color-coded dots on the mobile represent neurotransmitters. If doctors or researchers tug at one, the others follow until a new state is reached.
“The mobile looks simple, although it takes into account the underlying complex interactions among neurotransmitters that determine the nodes in the mobile,” Qi said.
With a few months’ work, a graphic user interface could be constructed to allow doctors and researchers to easily use Georgia Tech’s new computational model.