| Paper authors: | Ruiyang Ge, Jonathan Downar, Daniel Blumberger, Zafiris Daskalakis, Raymond Lam, Fidel Vila-Rodriguez |
| Year of paper publication: | 2019 |
| Post authors: | Alice Erchov, Caleb Pozdnikoff, Sarah Kesler, Fidel Vila-Rodriguez |
| Download the research article: | Ge (2019) Functional connectivity of the anterior cingulate cortex predicts treatment outcome for rTMS in treatment-resistant depression at 3-month follow-up |
Introduction
Depression doesn’t just change the way we think and feel — it also changes the structure and function of our brain. Some studies have found that those with depression have a lower brain volume: meaning that the brain may be lacking in important connections across different regions. Less efficient communication across brain regions may explain significant symptoms of depression that negatively affect problem solving, memory, and emotional regulation. These changes are brain-wide — but, possibly, reversible with treatment. This means it is important for research to look at the “bigger picture” of how our brains work, instead of just their individual parts.
As mentioned in a few recent articles, different areas of our brain are always in “conversation” – coordinating their activity in order to do everything from seeing, talking, breathing, and even dreaming! This communication relies on a series of brain cells called neurons that carry the different signals our brains use to work and communicate. In the current study, the authors were interested in patterns of activity (networks) that are common across groups of people, as opposed to any one individual.
The authors of the current paper were wondering if brain-wide changes in structure (i.e., neurons) or function could predict whether someone with treatment-resistant depression will respond to repetitive transcranial magnetic stimulation (rTMS).
rTMS is a safe, non-invasive, and effective neurostimulation treatment that works by applying a metal coil to the scalp. This coil releases magnetic pulses that disrupt brain activity that is thought to be dysfunctional in depression. Interestingly, this works even for those who do not benefit from traditional antidepressant medications or are, in other words, treatment-resistant.
This is important because if researchers could predict who would benefit from treatment using these brain-based measures, clinical treatments can be more efficient and personalized to what an individual is most likely to respond to.
Methods
This study included 50 people with moderate or severe treatment-resistant depression. There were also 42 “healthy controls” (people without depression or other illnesses) that were used as a comparison group.
Individuals with depression received rTMS or its accelerated version, iTBS, every weekday for 4-6 weeks.
Brain activity was measured using something called functional magnetic resonance imaging (fMRI). Each person lies down in a tube-like scanner. This scanner uses very strong magnets and tracks how different molecules in the brain react to it. Areas of our brain that are very active use a lot of blood and oxygen for energy, when compared to areas of our brain that are not active. The fMRI detects these differences in blood and oxygen to determine what brian areas are working at any given time. For an additional video that explains how MRIs and fMRIs work, you can see here: https://youtu.be/4UOeBM5BwdY?si=qVcXgGJy2kDmiqSj.
There were 3 brain networks researchers were primarily interested in:
- The default mode network (DMN) is active when we are not actively thinking or focusing on anything in particular. This includes when our mind wanders or we daydream! This network is related to our creative thought, social cognition, and memory.
- The central executive network (CEN) involves primarily regions in the front of our brain and regulates important aspects of cognition. For instance, the CEN is responsible for our ability to remain focused on a task and filter out distractions, control our impulses, and problem solve.
The salience network (SN) includes deeper regions of our brain. It is responsible for dictating where we place our attention (i.e., what is important) and our motivations.
Results
- There were no differences in depression improvement between those who received rTMS or iTBS
- Interestingly, there were no differences in the function of these networks (the DMN, CEN, or SN) between those with or without depression
- There were no structural differences in the default mode network or salience network between groups
- People with depression who did not respond to treatment, however, did have weaker structural connections among regions in the central executive network
- This means this network may be less efficient in its communication
- This disruption may underlie cognitive difficulties and symptoms in those with depression, especially with goal-directed tasks (actions taken to achieve a certain outcome) and memory, impulse control, cognitive flexibility, problem-solving, and emotion regulation
- Because those with a more severely disrupted central executive network were also less likely to achieve clinical remission from depression after rTMS treatment, this could be an important signal in predicting treatment response
- This could be because one of the important regions of the CEN, the dorsolateral prefrontal cortex, is the primary target of rTMS treatment
- This may mean that this region is more poorly-connected with the rest of the network and it may be more difficult for rTMS treatment to have positive effects, brain-wide
Conclusion
Those with depression who did not achieve clinical remission from the illness after a course of rTMS had, on average, more weakly connected brain regions involved in the central executive network. This would explain a lot of commonly-seen symptoms of depression, including difficulties with memory, problem-solving, and emotional regulation. Importantly, these differences may be able to predict who would respond to rTMS, meaning that clinicians and researchers in the future may be able to better direct people to whatever treatment is best for them.