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Repairing Shorts In the Brain’s Electrical Circuitry

A “short” in the brain’s electrical circuitry is implicated in many neurological and psychiatric disorders, including stroke, Parkinson’s disease, attention disorders and major depression to name a few.


“In many ways the brain resembles a large-scale computer network, with hubs and connections that communicate information, divvy up demanding processing tasks, and working together in a coordinated and dynamic way to accomplish the physical and mental functions that we find essential in day-to-day life,” said Roy Hamilton, MD, MS, an assistant professor of Neurology and Physical Medicine and Rehabilitation and the director of Penn’s Laboratory for Cognition and Neural Stimulation. Much like the server in an office, when a vital hub malfunctions, it can have a domino effect that negatively influences the entire system.

At Penn, researchers are studying new treatments and testing new devices that stimulate the brain circuitry using transcranial magnetic stimulation (TMS), a technique that has been around since the mid-1980s and uses electromagnetic pulses via a powerful magnetic coil placed on the scalp. This can modulate brain activity and potentially provide patients with new options to manage their neuropsychiatric conditions. Its applications grow as research into the therapy expands.

In April, Hamilton presented research at the American Academy of Neurology’s annual meeting introducing a new a new brain mapping model which could improve the success rate of TMS. The device creates electric currents that engage nerve cells in the part of the brain involved in thinking, perceiving, planning, and understanding language. Through this form of neuromodulation, improvements in have been achieved. But, the technique hasn’t worked for everyone.

Lead researcher John D. Medaglia, PhD, a postdoctoral fellow in Hamilton’s lab, said that the challenge was to identify the best possible location for placing the coil in order to generate good results. Medaglia and colleagues developed a model that emphasizes precision in placement as a precursor to enhanced results. It utilizes 3-D brain data to make informed inferences about optimal placement of the coil during treatment. 

“Placing the coil even millimeters or centimeters away from the optimal location could result in the treatment being partially or completely ineffective,” Medaglia said. “Our model relies on extensive knowledge of connections between brain regions to guide clinicians in best positioning the electromagnetic coil. This new way of thinking about brain networks and how to modulate their activity to could lead to better informed, neuroscience-driven TMS therapies that optimize the therapeutic effects of TMS.”

Neural oscillation, the brain’s electrical activity, is visible on an EEG and represents the rhythmic, repetitive neural activity that plays a role in regulating thinking and memory and mood. Many patients who have major depression are known to have abnormalities in their EEG. Restoring these abnormalities to a normal rhythm has been found to be an effective means of treatment.

Recently, Penn’s department of Psychiatry was one of the largest test sites in the country to review the safety and effectiveness of a new TMS device that aims to treat major depression by combining EEG technology with TMS technology, a process known as sTMS, thus making it unique in comparison to the current FDA-approved forms of TMS.

The study looked at over 200 subjects who had major depression; some who had never before been treated for the condition and some for whom prior antidepressant treatment had failed. The study found sTMS therapy to be more effective than sham placebo, with 34 percent of patients who received sTMS treatment showing a positive response as compared to eight percent of those who were treated with an inactive device. Further, more patients who had failed to receive benefit from prior antidepressant therapies were more likely to show a significant benefit from the treatment.

Researchers theorize that this process may lead to successful treatment while using less energy which would mitigate side effects from treatment which can include headache, pain and seizures, though no adverse events were reported in this study.

“This is a promising new non-medication treatment for depressed patients with new onset depression or depression that does not adequately respond to antidepressant medication,” said Mahendra Bhati, MD, assistant professor of Clinical Psychiatry and a clinical investigator on the study.  

“As we continue to study TMS,” Hamilton said, “we hope to better understand how to appropriately target the neural system and deliver this therapy so that we can know with certainty whether these treatments will succeed.” 

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