Left: A christmas tree with string lights working in an electrical circuit. Right: A representation of brain's electrical circuit
You Can't See It (The Brain), It's Electric
Imagine holiday season in December. People hang beautiful, decorative strings of lights; but sometimes a bulb burns out. When it’s just one light bulb, it’s easy to identify and replace. When a series of consecutive bulbs burn out, it’s much harder to figure out what went wrong and which bulb to replace. This same concept is applied to neuroscience. Much like holiday lights, the brain is represented by electrical circuits. Mental illnesses like depression, schizophrenia, or anxiety disorders occur when certain regions of the brain have trouble communicating with each other, or when multiple light bulbs burn out.
You might have heard mental illness described as a “chemical imbalance.” This is partially true. For example, in depression, there are losses of neurotransmitters like dopamine (reward, motivation, and movement) or serotonin (happiness). Neurotransmitters are chemicals that move across the brain and send messages like "I'm tired, let's go to sleep." In many mental illnesses, these messages are lost because the brain is no longer communicating as well. It's like if people were playing a game of telephone and the middle people ignored the message. There are certain medications like antidepressants (e.g. Prozac) or antipsychotics (e.g. Haldol) that help people with mental illness feel better by restoring the normal levels of neurotransmitters.
Drugs are designed to bind to the natural receptors that already exist in your body. Neurotransmitter receptors are not just found in our brain, but all over our body. Interestingly, the majority of serotonin is actually produced in the gut. Unfortunately, these medications do not help the majority of people with mental illness and usually cause more harm than good. Additionally, these medications can take weeks to months before having any positive effect. Drugs often are “promiscuous” or bind with too many receptors or “off targets”. Off target binding causes detrimental side effects like suicidal ideations, sleep disruptions, irritability, loss of movement, extreme weight loss/gain, psychosis, and more.
My research focuses on trying to improve mental illness treatments to reduce the number of side effects people experience. I am trying to do this in two ways
Imagine holiday season in December. People hang beautiful, decorative strings of lights; but sometimes a bulb burns out. When it’s just one light bulb, it’s easy to identify and replace. When a series of consecutive bulbs burn out, it’s much harder to figure out what went wrong and which bulb to replace. This same concept is applied to neuroscience. Much like holiday lights, the brain is represented by electrical circuits. Mental illnesses like depression, schizophrenia, or anxiety disorders occur when certain regions of the brain have trouble communicating with each other, or when multiple light bulbs burn out.
You might have heard mental illness described as a “chemical imbalance.” This is partially true. For example, in depression, there are losses of neurotransmitters like dopamine (reward, motivation, and movement) or serotonin (happiness). Neurotransmitters are chemicals that move across the brain and send messages like "I'm tired, let's go to sleep." In many mental illnesses, these messages are lost because the brain is no longer communicating as well. It's like if people were playing a game of telephone and the middle people ignored the message. There are certain medications like antidepressants (e.g. Prozac) or antipsychotics (e.g. Haldol) that help people with mental illness feel better by restoring the normal levels of neurotransmitters.
Drugs are designed to bind to the natural receptors that already exist in your body. Neurotransmitter receptors are not just found in our brain, but all over our body. Interestingly, the majority of serotonin is actually produced in the gut. Unfortunately, these medications do not help the majority of people with mental illness and usually cause more harm than good. Additionally, these medications can take weeks to months before having any positive effect. Drugs often are “promiscuous” or bind with too many receptors or “off targets”. Off target binding causes detrimental side effects like suicidal ideations, sleep disruptions, irritability, loss of movement, extreme weight loss/gain, psychosis, and more.
My research focuses on trying to improve mental illness treatments to reduce the number of side effects people experience. I am trying to do this in two ways
- Studying a drug that send messages to more specific brain regions
- Recording electrical activity in the brain.
Studying a Drug that Send Messages to More Specific Brain Regions
Antipsychotic drugs treat schizophrenia, a psychiatric illness characterized by psychosis, loss of motivation and pleasure, and difficulty thinking. Previous antipsychotic drugs acted as dopamine antagonists or drug that decrease dopamine in the brain. This drug treatment would be effective if there was a universal increase of dopamine everywhere in the brain. However, people with schizophrenia often have a loss of dopamine in the prefrontal cortex (thinking brain area) and an increase of dopamine in the striatum (reward brain area).
Antipsychotic drugs negatively affect the prefrontal cortex and patients report feeling severely depressed, having memory loss, and having extreme mood swings. The ideal antipsychotic drug treatment would act like a thermostat: If the temperature in the room is lower than idea, the thermostat would increase the temperature (dopamine agonist) versus if the temperature in the room is higher than ideal, the thermostat would decrease the temperature (dopamine antagonist). This “thermostat” antipsychotic is called a partial agonist because it can decrease and increase neurotransmitters at the same time. I study a new antipsychotic drug and dopamine partial agonist, UNC9994A (94A) and measure how much it interacts with dopamine in different parts of the brain. If my research in mice shows improvement in memory and thinking and also reduce psychosis, then 94A could help patients with schizophrenia without causing the painful side effects.
Antipsychotic drugs treat schizophrenia, a psychiatric illness characterized by psychosis, loss of motivation and pleasure, and difficulty thinking. Previous antipsychotic drugs acted as dopamine antagonists or drug that decrease dopamine in the brain. This drug treatment would be effective if there was a universal increase of dopamine everywhere in the brain. However, people with schizophrenia often have a loss of dopamine in the prefrontal cortex (thinking brain area) and an increase of dopamine in the striatum (reward brain area).
Antipsychotic drugs negatively affect the prefrontal cortex and patients report feeling severely depressed, having memory loss, and having extreme mood swings. The ideal antipsychotic drug treatment would act like a thermostat: If the temperature in the room is lower than idea, the thermostat would increase the temperature (dopamine agonist) versus if the temperature in the room is higher than ideal, the thermostat would decrease the temperature (dopamine antagonist). This “thermostat” antipsychotic is called a partial agonist because it can decrease and increase neurotransmitters at the same time. I study a new antipsychotic drug and dopamine partial agonist, UNC9994A (94A) and measure how much it interacts with dopamine in different parts of the brain. If my research in mice shows improvement in memory and thinking and also reduce psychosis, then 94A could help patients with schizophrenia without causing the painful side effects.
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Recording Electrical Activity in the Brain
Every time brain cells, or neurons, communicate with each other, there are changes in electrical activity called action potentials. Neurotransmitters also have positive, negative, or neutral electrical charges. Much like if you stuck a metal fork in the wall (don’t), you would pick up electrical currents; implanting metal wires, or electrodes, in the brain allows us to measure its electrical activity. Previous neuroscience research has largely focused on recording one to two brain regions at a time. However, our brain works by connecting multiple brain regions in a circuit. For example, when you eat your favorite food, the brain regions involved with taste, smell, sight, memory, movement, reward, and hunger are all communicating I record electrical activity from dozens of different brain regions at the same time to try to best learn natural human behavior.. To study mental illness, I record from brain regions involved with thinking, memory, socializing, motivation, reward, and emotions. If I learn the electrical patterns neurotransmitter of how a healthy (without mental illness) brain communicates, I can then compare what changes in a disease state brain (with mental illness) and design an electrical stimulation to restore the neural activity. Transcranial magnetic stimulation (TMS) is a non-invasive (does not require surgery) clinical technique that stimulates neurons by directing electric currents to specific brain areas. TMS has been effective in improving quality of life for some patients with depression and these positive changes happen much quicker than pharmacological treatments. Importantly, targeting specific brain regions with electrical stimulation has less off target interactions, thus produces less bad side effects. In the future, it may be possible to apply TMS to a variety of other mental illnesses. Not only could electrical treatment result in fewer side effects, but it could also lead to precision medicine, clinical treatment tailored for you. Just like everyone has their own DNA, we all have individual experiences and environments that affect our brain activity. Rather than prescribing every patient with depression Prozac, we could learn their individual electrical brain activity and create a specific stimulation program to help them. |
Left: A disease state brain (with mental illness); the blacked out circles represent brain regions that have "burnt out lights" or are unable to communicate in the neural circuit. Right: Electrical stimulation like TMS could help restore neural activity and improve quality of life for someone living with a mental illness.
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