As society returns to what life was like before the pandemic, many people are glad to again hang out with friends, attend concerts and travel.

For others, however, the idea of being around others can cause a crippling dread of social interaction called Social Anxiety Disorder (SAD).

SAD is one of the most common mental disorders in the United States, affecting 15 million adults and about 12 percent of the population at any given time, according to the Anxiety & Depression Association of America (ADAA) and the National Institute of Mental Health.

Ryan Wagoner, MD, associate professor of psychiatry in the USF Health Morsani College of Medicine, said SAD is different from simply being shy, which he called a “personality trait” and manifests itself in such instances as a person feeling awkward walking into a room full of strangers or being nervous before a blind date.

Ryan Wagoner, MD

“When people are placed in situations where they have to be scrutinized by other people—social settings (and) presentations … that’s when Social Anxiety Disorder can pop up,” Dr. Wagoner said.

SAD, on the other hand, can cause intense stress that affects a person’s life. For example, someone living with SAD may turn down a promotion that involves public speaking or refusing to attend social and work parties.“When people are placed in situations where they have to be scrutinized by other people—social settings (and) presentations … that’s when Social Anxiety Disorder can pop up,” Dr. Wagoner said.

“There’s no hard and fast rule that COVID was good or bad for Social Anxiety Disorder—it was both,” he said.

As people ease their way back into normal levels of social interaction, Dr. Wagoner said it was important for people who think they have SAD to pace themselves and watch out for warning signs of acute anxiety.

“People with Social Anxiety Disorder need to figure out what they are comfortable with doing because if they put themselves in very uncomfortable situations without the appropriate support then they can be right back into some of those acute episodes,” Dr. Wagoner said.

Common symptoms of SAD, according to the ADAA, include:

• Fear of being visibly nervous in front of others
• Extreme anticipatory anxiety about social interactions and performance situations, such as speaking to a group
• Severe fear of not knowing what to say
• Avoiding face-to-face interactions by depending on technology
• Fear of eating in public
• Using alcohol or substances to function in social situations

Most people who seek treatments for SAD do improve and enjoy a better quality of life, Dr. Wagoner said. Treatments include cognitive-behavioral therapy and/or medication.

“Why not pursue treatments in order to try to make life better?” he said

Video & Article: Allison Long

First-in-human study of diffuse optical tomography during rTMS suggests treatment target or parameters may need adjusting to benefit more patients with severe depression

TAMPA, Fla. (May 4, 2021) — Repetitive transcranial magnetic stimulation, or rTMS, was FDA approved in 2008 as a safe and effective noninvasive treatment for severe depression resistant to antidepressant medications. A small coil positioned near the scalp generates repetitive, pulsed magnetic waves that pass through the skull and stimulate brain cells to relieve symptoms of depression. The procedure has few side effects and is typically prescribed as an alternative or supplemental therapy when multiple antidepressant medications and/or psychotherapy do not work.

Despite increased use of rTMS in psychiatry, the rates at which patients respond to therapy and experience remission of often-disabling symptoms have been modest at best.

Now, for the first time, a team of USF Health psychiatrists and University of South Florida biomedical engineers applied an emerging functional neuroimaging technology, known as diffuse optical tomography (DOT), to better understand how rTMS works so they can begin to improve the technique’s effectiveness in treating depression. DOT uses near-infrared light waves and sophisticated algorithms (computer instructions) to produce three-dimensional images of soft tissue, including brain tissue.

Shixie “Max” Jiang, MD, (above) a third-year psychiatry resident in the USF Health Morsani College of Medicine, and his father Huabei Jiang, PhD, (below) a professor in the Department of Medical Engineering, collaborated on the study.

Comparing depressed and healthy individuals, the USF researchers demonstrated that this newer optical imaging technique can safely and reliably measure changes in brain activity induced during rTMS in a targeted region of the brain implicated in mood regulation. Their findings were published April 1 in the Nature journal Scientific Reports.

“This study is a good example of how collaboration between disciplines can advance our overall understanding of how a treatment like TMS works,” said study lead author Shixie Jiang, MD, a third-year psychiatry resident at the USF Health Morsani College of Medicine. “We want to use what we learned from the application of the diffuse optical tomography device to optimize TMS, so that the treatments become more personalized and lead to more remission of depression.”

DOT has been used clinically for imaging epilepsy, breast cancer, and osteoarthritis and to visualize activation of cortical brain regions, but the USF team is the first to introduce the technology to psychiatry to study brain stimulation with TMS.

“Diffuse optical tomography is really the only modality that can image brain function at the same time that TMS is administered,” said study principal investigator Huabei Jiang, PhD, a professor in the Department of Medical Engineering and father of Shixie Jiang. The DOT imaging system used for USF’s collaborative study was custom built in his laboratory at the USF College of Engineering.

A small coil positioned near the scalp generates repetitive, pulsed magnetic waves that pass through the skull and stimulate brain cells (neurons) to relieve symptoms of depression. A typical rTMS session lasts 30 to 60 minutes and does not require anesthesia.

The researchers point to three main reasons why TMS likely has not lived up to its full potential in treating major depression: nonoptimized brain stimulation targeting; unclear treatment parameters (i.e., rTMS dose, magnetic pulse patterns and frequencies, rest periods between stimulation intervals), and incomplete knowledge of how nerve cells in the brain respond physiologically to the procedure.

Portable, less expensive, and less confining than some other neuroimaging equipment like MRIs, DOT still renders relatively high-resolution, localized 3D images. More importantly, Dr. Huabei Jiang said, DOT can be used during TMS without interfering with treatment’s magnetic pulses and without compromising the images and other data generated.

DOT relies on the fact that higher levels of oxygenated blood correlate with more brain activity and increased cerebral blood flow, and lower levels indicate less activity and blood flow. Certain neuroimaging studies have also revealed that depressed people display abnormally low brain activity in the prefrontal cortex, a brain region associated with emotional responses and mood regulation.

By measuring changes in near-infrared light, DOT detects changes in brain activity and, secondarily, changes in blood volume (flow) that might be triggering activation in the prefrontal cortex. In particular, the device can monitor altered levels of oxygenated, deoxygenated, and total hemoglobin, a protein in red blood cells carrying oxygen to tissues.

Above: Cross-sectional 3D images of brain activity (red to yellow) in healthy volunteers, reconstructed from total hemoglobin data collected by diffuse optical tomography. Data from the brain’s right side only was acquired during a 30-second period of rTMS. The bronze coil symbol represents stimulation of the left side. Below: 3D images using the same rTMS protocol in depressed participants indicate minimal or no brain activity. | Photos courtesy of Shixie Jiang, MD

The USF study analyzed data collected from 13 adults (7 depressed and 6 healthy controls) who underwent DOT imaging simultaneously with rTMS at the USF Health outpatient psychiatry clinic. Applying the standard rTMS protocol, the treatment was aimed at the brain’s left dorsolateral prefrontal cortex – the region most targeted for depression.

The researchers found that the depressed patients had significantly less brain activation in response to rTMS than the healthy study participants. Furthermore, peak brain activation took longer to reach in the depressed group, compared to the healthy control group.

This delayed, less robust activation suggests that rTMS as currently administered under FDA guidelines may not be adequate for some patients with severe depression, Dr. Shixie Jiang said. The dose and timing of treatment may need to be adjusted for patients who exhibit weakened responses to brain stimulation at baseline (initial treatment), he added.

Larger clinical trials are needed to validate the USF preliminary study results, as well as to develop ideal treatment parameters and identify other dysfunctional regions in the depression-affected brain that may benefit from targeted stimulation.

“More work is needed,” Dr. Shixie Jiang said, “but advances in neuroimaging with new approaches like diffuse optical tomography hold great promise for helping us improve rTMS and depression outcomes.”

The DOT device is connected to an individual’s scalp by fiber-optic cables comprised of source-detector sensors held in place by a modified EEG cap. The paired sensors both transmit the near-infrared light and convert light dispersed from brain tissue into the signals needed to reconstruct 3D brain images. | Photo courtesy of Huabei Jiang, PhD