| Paper authors: | Peter W. Fettes, Massieh Moayedi, Katharine Dunlop, Farrokh Mansouri, Fidel Vila-Rodriguez, Peter Giacobbe, Karen D. Davis, Raymond W. Lam, Sidney H. Kennedy, Zafiris J. Daskalakis, Daniel M. Blumberger, Jonathan Downar |
| Year of paper publication: | 2018 |
| Post authors: | Caleb Pozdnikoff, Lisa Ridgway, Anabelle McPherson, Fidel Vila-Rodriguez |
| Check out the full research article: | Fettes et al. (2018) Abnormal Functional Connectivity of Frontopolar Subregions in Treatment-Nonresponsive Major Depressive Disorder |
Introduction
People with depression have altered activity in some parts of the brain. To treat depression, we can attempt to change this altered activity by using neurostimulation techniques such as repetitive transcranial stimulation (rTMS). However, the brain region we typically apply rTMS to only achieves remission (disappearance of symptoms) rates of 30% to 35%. This has led researchers to look for different target regions that may lead to a higher remission rate.
Researchers have noticed that when the activity of a brain region called the frontopolar cortex (FPC) is altered, the severity of depressive symptoms can change. If this is the case, then could we apply rTMS to the FPC to change its activity levels and treat depression symptoms?
To tackle this question, the researchers of this paper try to verify the FPC’s role in depression by investigating if it is connected to other regions of the brain that are known to play roles in depression. They also examined if severity of depression symptoms change with the level of activity of these brain regions. This raises questions as to whether these less treated regions would be good targets for neurostimulation to improve depressive symptoms.
As mentioned in our other recent articles, different areas of our brain are always in “conversation” – coordinating their activity in order to do everything from seeing, talking, and breathing. Areas of our brain that are active or quiet at the same time are said to have “functional connectivity”.
If we know which brain regions (for example the FPC) are involved in depression, we may be able to target rTMS treatment more effectively.
Methods
56 people with treatment-resistant depression (TRD) completed this study. This group had to have tried, and not benefited from, at least one antidepressant in the past. There were also 56 “healthy controls” (people without depression or other illnesses) that were used as a comparison group.
As mentioned in several of our recent articles, brain activity was measured using something called functional magnetic resonance imaging (fMRI). Each person lies down in a tube-like scanner. This scanner is able to detect differences in blood and oxygen flow and usage in our brains and determine what brain areas are working at any given time. For an additional video that explains how MRIs and fMRIs work, check out this link: https://youtu.be/4UOeBM5BwdY?si=qVcXgGJy2kDmiqSj.
There are some brain regions that fire closely together to perform specific functions, and these are called networks. One network that is relevant in depression is the salience network (SN). The SN is related to regulating thoughts, behaviours, and emotional states. Another network involved in depression is the default mode network (DMN). The DMN is involved in introspection and rumination (repetitive thinking of negative emotions or thoughts).
The main brain area the researchers examined was the FPC. The study looked at the function of the medial FPC (mFPC, closer to the middle of the brain) and the lateral FPC (lFPC closer to the sides of the brain). These two sections have different connectivity and different functions. The mFPC is a region in the DMN, which is involved in rumination. The lFPC is associated with reward learning (changing behaviour in response to a reward).
The other examined brain area was the orbitofrontal cortex (OFC). There are two subregions of interest here: the medial OFC (mOFC) and the lateral OFC (lOFC). The mOFC plays a role in how the brain processes and responds to rewarding experiences. The lOFC helps to learn to stop responding to something that is no longer rewarding, and to help re-interpret situations.
Brain function measurements were compared between these 56 people with TRD and 56 “healthy controls” without depression. This way, this study could identify the way brain function was different among those with depression.
Results
- This study found that people with TRD had altered levels of functional connectivity between different brain regions and their networks
- The left mFPC showed reduced functional connectivity to the precuneus, a key region of the default mode network, involved in rumination
- The mFPC had decreased functional connections to brain regions in the salience network
- Since the salience network plays a role in regulating thoughts and emotional states, this may reflect the loss of control over rumination that people with depression experience
- People with TRD had altered levels of functional connectivity between the lFPC and the OFC
- The severity of depressive symptoms was found to be related to the functional connectivity between the lFPC and mOFC
Conclusion
People with treatment-resistant depression had different levels of functional connectivity in certain brain regions when compared to those without depression. Specifically, the coordination of activity between the FPC and OFC subregions may impact depressive symptoms and their severity. These findings suggest that additional regions (the FPC and OFC) could be targeted with neurostimulation techniques (such as rTMS) to potentially reduce depressive symptoms.
Future research is needed to confirm if these specific instances of decreased functional connectivity actually cause these TRD symptoms. Then additional studies will need to systematically test if new treatments aimed at these areas can truly help patients.