How depression impacts the brain

Depression is more than just feeling sad. It’s a medical condition that actually changes how key areas of the brain work, influencing mood, motivation, memory, and decision-making. These changes can make everyday life feel heavier, even when you’re doing everything “right.”

For many, therapy and antidepressant medications provide relief. But some people continue to struggle despite trying multiple treatments. That’s where Transcranial Magnetic Stimulation (TMS) can make a difference. TMS is a noninvasive, FDA-cleared therapy that targets underactive regions of the brain, helping restore healthier activity patterns and offering hope when other options haven’t worked.

In this blog, we’ll explore how depression impacts the brain and explain how, with the right support and treatment, the brain’s natural adaptability can make recovery possible.

How does depression affect the brain?

Depression affects how you feel, and it changes how your brain functions. Certain brain regions that control mood, memory, motivation, and decision-making can become disrupted.

Three key players are the hippocampus, amygdala, and prefrontal cortex.

1. The Hippocampus: Your memory and learning hub

The hippocampus helps turn short-term memories into long-term ones. It plays a major role in learning, recalling facts, finding the right words, and even remembering where your body is in space.

When depression goes untreated for a long time, research shows the hippocampus can actually shrink. This may help explain why people with depression often struggle with memory, concentration, and mental clarity.

The encouraging news? Studies suggest these changes can improve with effective treatment.

2. The Amygdala: Your emotional alarm system

The amygdala processes emotions, especially strong ones like fear, sadness, and anger. It continuously scans the environment for threats and determines how the body should respond.

In depression, the amygdala is often overactive, particularly when interpreting negative experiences. This means the brain can react as if something is wrong even when you’re safe. Small setbacks may feel overwhelming, and neutral situations may be interpreted more negatively than they really are.

3. The Prefrontal Cortex: Your planning and decision-making center

The prefrontal cortex is often called the brain’s “executive center.” It helps you plan, set goals, solve problems, regulate emotions, and make decisions. It’s where insight, foresight, and self-control come together.

In people with depression, this region often shows reduced activity. The more severe the depression, the more pronounced this reduction can be.

When the prefrontal cortex isn’t working at full capacity:

• Goals can feel unreachable
• Motivation drops
• Decision-making becomes harder
• The downsides of situations seem larger than the potential benefits

This can create a cycle where negative thinking reinforces low mood and hopelessness.

For some people, antidepressant medications help rebalance these systems. But depression is complex, and not all brains respond the same way.

What is treatment-resistant depression?

Treatment-resistant depression (TRD) is depression that hasn’t improved after trying at least two antidepressant medications at an adequate dose and duration.

Many individuals with depression try:

• Multiple antidepressants in search of one that works
• Medication combinations, including “adjunct” medications that are added to treatment to enhance effectiveness or relief, or manage side effects
• Psychotherapy or talk therapy
• More intensive treatments such as electroconvulsive therapy (ECT)

Yet symptoms persist. That’s where TMS offers a different approach.

What is TMS?

Transcranial Magnetic Stimulation (TMS) is a noninvasive, FDA-cleared treatment that uses low-intensity magnetic pulses to stimulate specific brain regions involved in mood regulation.

Cleared by the FDA in 2008 for major depressive disorder, TMS is now also used to treat OCD and help with smoking cessation. TMS can be a powerful alternative for individuals who haven’t found enough relief from medication alone or who prefer a non-medication option.

If you’re searching for TMS therapy for depression or non-medication treatment for depression, this safe and innovative approach may be worth exploring.

How does TMS work?

Think of TMS as a way to “wake up” underactive areas of the brain linked to depression.

Unlike antidepressants, which travel through the bloodstream and affect the entire body, TMS treatment is localized. It targets specific brain regions, particularly the prefrontal cortex,  without impacting other organs.

During a TMS session:

• A small treatment coil is placed comfortably against your scalp
• The device delivers precise magnetic pulses
• These pulses create tiny electrical currents in the brain
• The currents stimulate underactive nerve cells in the prefrontal cortex (the area tied to mood, motivation, and decision-making)
• Over time, repeated sessions help retrain neural pathways and promote healthier brain activity

There’s no surgery. No anesthesia. No downtime.

Sessions are brief, and clients remain awake and alert. Many return to work, school, or daily activities immediately after treatment.

You can watch this video to understand how Rosecrance Therapies treats TMS.

What does TMS treatment look like?

Because TMS is noninvasive, treatment fits easily into daily life. During sessions, many clients read, scroll on their phone, or chat with the technician.

Since TMS works cumulatively, consistency is key. Repeated stimulation encourages the brain to fire in healthier, more balanced patterns.

Most clients can expect:

• Sessions lasting about 20 minutes
• Treatment five days per week
• A minimum of six weeks of care

Your provider will determine the exact plan based on your needs.

How long does TMS take to work?

TMS is not an overnight fix, but many clients notice meaningful improvement within 2 to 4 weeks. For comparison, antidepressant medications often take 4–8 weeks to reach full effectiveness.

Clients receiving TMS treatment commonly describe:

• A noticeable “lifting” of mood
• Feeling lighter or less weighed down
• Increased motivation
• More spontaneous smiling or humor

In some cases, loved ones notice positive changes even before a client does.

Is TMS safe?

For most people, TMS is safe to use. Compared to medications, TMS side effects are generally mild and temporary.

The most common include:

• Mild scalp discomfort during early sessions
• Temporary headache
• Brief facial muscle tightening (adjustable through positioning)
• Occasional fatigue after sessions

There are no long-term systemic side effects, because the treatment is localized to a specific brain region.

Do people stay on medication during TMS?  

Most providers recommend keeping medications stable before and during TMS treatment and avoiding medication changes during the six-week protocol.

After completing TMS, some clients may work with their provider to adjust or reduce medications. Others remain on medication and use TMS as added support.

Importantly, TMS is a treatment, not a permanent cure. Depression is often a chronic condition. However, relapse rates after successful TMS are relatively low, and if symptoms return, many clients respond again to another TMS course.

The bigger picture

Depression is not a personal weakness, a lack of willpower, or a character flaw.

It involves real, measurable changes in how the brain processes emotion, motivation, and hope. Understanding this can be incredibly freeing. It replaces shame with science and self-criticism with compassion.

More importantly, these brain changes are not permanent. The brain is adaptable. It can heal. With the right support, new patterns can form, activity can rebalance, and symptoms can improve.

Sometimes the brain needs the right kind of support — or the right kind of stimulation — to begin that healing process.

At Rosecrance Therapies, our clinicians in Chicago and Rockford provide a full spectrum of evidence-based treatments for depression. For some, this may include traditional approaches such as talk therapy and medication management. For others, innovative treatments such as TMS can help stimulate underactive areas of the brain linked to mood and motivation.