Study shows how rTMS treatment alters neural connections throughout the brain in patients with treatment-resistant depression, providing clues to predict who will benefit

Over the past decade, rTMS (Repetitive Transcranial Magnetic Stimulation), a form of non-invasive brain stimulation, has become a first-line treatment option for patients with depression, including those with depression. Major Depressive Disorder (MDD) Those who have not responded to multiple courses of other antidepressant therapy.

rTMS helps reduce symptoms of depression in a significant proportion of treatment-resistant MDD patients. This has a very beneficial impact, as her treatment-resistant MDD patients are often handicapped by their condition and are at high risk of suicide.

Why might rTMS help reduce symptoms of depression, and are there ways to determine who might benefit most before treatment? Answers about its mechanism of action Experts have long believed that the magnetic pulses that rTMS delivers to a brain region called the dorsolateral prefrontal cortex (DLPFC), just below the scalp, have the effect of altering the plasticity of neurons in that brain. I came. region, and possibly other regions to which it is connected.

Broadly speaking, altering plasticity means altering the strength of connections between brain regions, making them stronger or weaker. (Both could have therapeutic effects, depending on the context.) If rTMS acts by altering neuroplasticity, this would support an important theory about the cause of depression. The “neural plasticity hypothesis” proposes that dysfunction of neuroplasticity is at least one of the key underlying mechanisms that cause disease.

A research team led by Fidel Vila-Rodriguez, MD, Ph.D. at the University of British Columbia wanted to learn more about the relationship between the therapeutic effects of rTMS and plasticity. They investigated how a single rTMS application alters neuroplasticity. This is inferred from changes in functional connectivity throughout the brain, not just his DLPFC, which is a therapeutic target. They also sought to discover whether these connectivity patterns after a single rTMS session could be used to predict which MDD patients would be most helped by a subsequent 4-week course of rTMS treatment.

they the result American Journal of Psychiatry. Sophia Frangou, MD, Ph.D., 2019 BBRF Corvin Award Winner, 2008 BBRF Independent Investigator, 2002 BBRF Junior Investigator.and Sean Nestor, M.D., Ph.D.The 2022 BBRF Young Investigator was a member of the team. Dr. Ruiyang Ge was the first author of this paper.

Researchers recruited 52 patients with treatment-resistant MDD for a trial to measure the impact of a 4-week course of rTMS therapy. Of these, 38 patients (26 female, mean age 42) consented to participate in a separate study that included performing her one rTMS session prior to initiation of the course of treatment. . These patients underwent this initial rTMS session while inside a scanner that produced functional MRI images of brain activity in real time. The patient then underwent her 4 weeks of rTMS treatment.

The investigators found that rTMS stimulation of the right DLPFC “induced extensive acute changes in functional connectivity,” and that these changes “predicted clinical outcome after a 4-week course of rTMS treatment.” bottom.

The team made a number of interesting observations in addition to this conclusion. They argued that “widespread connectivity changes [brain] Correlate “regions of unknown functional or anatomical relevance” with DLPFC, the site of interest for treatment. Importantly, the known connection pattern of the DLPFC “adds to the evidence that rTMS can affect functional brain organization beyond expectations,” they say.

This suggests to the team that one of the reasons why rTMS is effective in depression is its ability to alter connectivity at the ‘macro level’. Various symptoms (for example, depressed mood, suicidal tendencies, difficulty finding pleasure). In general, changes in connectivity noted after rTMS were decreases in baseline connectivity, not increases.

It was also interesting to note that the changes in connectivity seen after the first rTMS session, while significant, were short-lived. This suggests to the team why repeated stimulation sessions, longer sessions, or sessions delivering more magnetic pulses are needed to produce clinical improvement in rTMS therapy.

Finally, the team commented on the predictive value of changes in functional connectivity observed after the first rTMS session. There was an association between the level of change in connectivity at that first session and treatment response after the 4-week treatment course. Patients who showed the most significant changes in the first session tended to benefit more from the entire course of treatment. We propose that the preliminary fMRI readout of 100% could potentially be used as an indicator of an individual patient’s ability to respond to a full course of therapy.

The results of this study need to be replicated in a larger cohort, including a control group, and trials comparing results targeting the appropriate DLPFC to other rTMS targets, the team noted.