TMS and the Function of the Dorsolateral Prefrontal Cortex

Transcranial Magnetic Stimulation (TMS) is a non-invasive procedure that uses magnetic fields to stimulate nerve cells in the brain. A primary target is the dorsolateral prefrontal cortex (DLPFC), a functional area in the frontal lobes. TMS is often considered when other depression treatments have been ineffective.

The Function of the Dorsolateral Prefrontal Cortex

The dorsolateral prefrontal cortex is a functional area in the frontal part of the brain, defined by its connections and roles. The DLPFC is a central hub for executive functions. These cognitive processes include working memory, which allows for the temporary holding and manipulation of information, and cognitive flexibility, the ability to switch between tasks.

This brain region is also involved in planning, abstract reasoning, and decision-making. The DLPFC has extensive connections to other brain areas involved in emotion, such as the amygdala, and motor planning. These connections allow it to receive information from and regulate the activity of these other regions.

The DLPFC also plays a role in mood regulation by exerting an inhibitory influence over brain structures like the amygdala, which processes emotions. Dysfunction in the DLPFC, particularly reduced activity (hypoactivity), is linked to major depressive disorder (MDD). This can lead to difficulty regulating negative emotions and symptoms like trouble concentrating and making decisions.

Mechanism of Action in TMS Therapy

TMS therapy uses an electromagnetic coil placed against the scalp. This coil generates brief, powerful magnetic pulses that pass through the skull, inducing small electrical currents in the underlying brain tissue. For treating depression, the primary target is the left DLPFC, a region that often shows reduced activity in affected individuals.

The induced electrical currents cause neuronal depolarization, which is the process of nerve cells firing. When applied in a repetitive sequence (rTMS), these stimulations can lead to lasting changes in brain function. The goal of high-frequency rTMS on the left DLPFC is to increase its excitability and activity levels, correcting the hypoactivity associated with depression.

Repeated stimulation sessions harness the brain’s neuroplasticity, its ability to reorganize and form new neural connections. This therapy aims to increase activity in the underactive DLPFC, improving communication within the brain’s mood-regulating circuits. TMS can also affect blood flow and connectivity in deeper, interconnected brain regions.

The Treatment Process

The TMS process begins with an initial consultation and a “brain mapping” session to identify the precise location of the patient’s left DLPFC. Next, a clinician determines the motor threshold, the minimum magnetic energy needed to cause a small thumb twitch. This step calibrates the correct “dose” or intensity of stimulation for treatment.

During treatment, the patient is seated comfortably in a reclining chair and remains awake and alert. The electromagnetic coil is placed against the head at the mapped location, and earplugs are provided for the machine’s clicking sound. Patients often describe the sensation as a tapping on their scalp.

A standard course of TMS involves daily sessions, five times a week, for four to six weeks, with each session lasting 20 to 40 minutes. Since the procedure requires no anesthesia or sedation, patients can immediately return to their daily activities afterward.

Clinical Applications and Effectiveness

The primary clinical application for TMS targeting the DLPFC is treating Major Depressive Disorder (MDD), particularly for individuals who have not responded to antidepressant medications. The U.S. Food and Drug Administration (FDA) approved TMS for depression in 2008. It is also FDA-approved for Obsessive-Compulsive Disorder (OCD) and smoking cessation, though specific brain targets may differ.

Effectiveness is measured by “response” (a significant symptom reduction) and “remission” (symptoms have almost completely gone away). For treatment-resistant depression, large-scale studies report remission rates around 30-40% and response rates between 50% and 55%.

The therapeutic effects of TMS are not immediate, as patients often notice improvements in their mood and other symptoms after a few weeks of consistent daily treatments. Following a full course, some patients may be advised to continue with maintenance therapy, like medication or psychotherapy, to prevent symptom relapse.

Safety Profile and Candidacy

TMS therapy is considered safe and well-tolerated. Good candidates are adults with Major Depressive Disorder who have not experienced satisfactory improvement with antidepressant medications. Because its effects are localized, TMS avoids the systemic side effects associated with many antidepressant drugs, such as weight gain or sexual dysfunction.

The primary contraindication for TMS is the presence of metal in or near the head, such as cochlear implants or aneurysm clips, as the magnetic fields can displace or heat them. Individuals with a history of seizures or epilepsy are also advised to be cautious, as the procedure carries a small risk of inducing one.

The most common side effects are mild and temporary. These can include:

• Headaches or discomfort at the stimulation site on the scalp
• Lightheadedness
• Twitching of facial muscles during the treatment

These sensations resolve shortly after the session ends. Serious side effects are rare.