Understanding the E - I Imbalance Theory of Autism

In PlainSpeak for the Lay Reader

Caveat: Always keep in mind there is no single theory that perfectly explains autism.

The Excitatory-Inhibition (E-I) Imbalance idea says that a mix-up between signals that excite and calm the brain can cause the sensory, thinking, and behavior issues in autism.

What Can Cause the E-I Imbalance?

Too Much Glutamate and Overactive Exciting Neurons
Glutamate is the main chemical that makes brain cells more active. If there is too much glutamate or the exciting neurons are too active, it can make the brain overly excitable. This can cause people with autism to be very sensitive to sounds, lights, and other sensory inputs and make thinking and processing information harder.

Not Enough GABA to Calm the Brain
GABA is the main chemical that calms brain cells. In autism, there can be less GABA, problems with GABA receptors, or less active calming neurons. This means the brain doesn’t have enough calming signals to balance the exciting ones, making the E-I imbalance worse.

Problems with Exciting and Calming Neurons
Neurons are the cells in the brain that send and receive signals. Exciting neurons make other neurons more active, while calming neurons reduce activity. In autism, there might be differences in the number, function, or connections of these neurons. For example, changes in certain calming neurons can disrupt the brain’s local circuits, leading to more excitement and less calming.

Important Development Periods
The E-I balance is especially important during key development times when the brain is growing and changing rapidly. If the balance is off during these times, it can affect brain development and function in the long term. This can impact learning, memory, and the formation of proper brain connections.

Changes in Synaptic Proteins

Proteins like neuroligins and neurexins help brain cells stick together and send signals. In autism, changes or problems with these proteins can lead to abnormal connections between brain cells, affecting the E-I balance.

Ion Channel Problems
Ion channels help neurons send signals by letting ions in and out. Ions are tiny charged particles, like sodium, potassium, or calcium, that neurons need to function properly. In autism, problems with these ion channels can change how neurons send signals, affecting the E-I balance.

Problems with Synaptic Plasticity
Synaptic plasticity is the ability of connections between brain cells to get stronger or weaker over time. This is important for learning and memory. Long-term potentiation (LTP) is when these connections get stronger with activity, helping with learning new things. Long-term depression (LTD) is when these connections get weaker, which helps remove unnecessary information. In autism, problems with LTP and LTD can make it harder to learn and remember things.

Role of Supporting Brain Cells (Astrocytes and Microglia)
Astrocytes and microglia are supporting cells in the brain that help maintain E-I balance. Astrocytes manage levels of glutamate and GABA, while microglia help prune synapses during development. Pruning is like trimming a tree; it removes extra connections between brain cells to make the network more efficient. Problems with these cells can lead to too much excitation or not enough inhibition.

Genetic and Epigenetic Factors
Our genes, which are like instructions for how our body works, can influence the E-I balance. Changes in how these genes are turned on or off can also affect the brain. Many genes linked to autism affect how brain cells connect and communicate, leading to differences seen in autism.

Environmental Influences
Things in the environment, like exposure to toxins, infections, and stress during pregnancy, can impact the E-I balance. These factors can change how the brain develops and works, leading to long-term effects on brain signals.

• 2 versions of this post: 
• For the Scientific/Academic Audience
• PlainSpeak / Plain Language for the Lay Reader