When the first TMS device (Neurostar) was FDA cleared for major depressive disorder (MDD) in 2008, the FDA label defined the dorsal lateral pre-frontal cortex (DLPFC) target based on a scalp-based targeting strategy. Specifically, the TMS operator would first need to identify where the motor region of the brain was (based on a visible hand twitch) then move 5 cm forward. The DLPFC target was defined as the region that was 5 cm forward of the “motor hotspot” for the hand (the putative scalp region representing the hand region of the primary motor cortex (M1). This is a highly reliable strategy that does not require any additional equipment and for most individuals will adequately target the DLPFC. Since 2008 multiple other TMS devices have come on the market and received FDA clearance for MDD. Most of these devices also use the “5 cm rule.” There are two notable exceptions to this rule. The first, the Brainsway device, is not a single focused field, but the position of the “helmet” is also based on scalp measurements. The second exception is the Nexstim “Navigated Brain Therapy” (NBT) System. The NBT system uses individualized structural MRI-based targeting.
So, what is the difference and why is it important? In order to explain, I’d like to use an analogy. Imagine your brain is a city and the regions of the brain are neighborhoods, and the connections between the regions are roads. Now imagine that you’ve never been to this city, which is pretty accurate, as each brain and mind is unique and even the most experienced Neurologist or Psychiatrist may have never met a brain or mind like yours! Now you need to get to a specific building in a neighborhood called “DLPFC” (This would be analogous to the specific region of DLPFC that would be optimally therapeutic for you). You are staying at a hotel in a neighborhood called “M1” and the hotel is the tallest building in the city, super easy to find. You don’t need a map or GPS to find your hotel. DLPFC on the other hand is harder to find. There are no signs that tell you that you are in DLPFC, but that is where you need to go. To get to DLPFC you can choose between using a GPS or following the written directions from your friend who also stayed at the same hotel and wrote down how she got to DLPFC. It’s not that one is better than the other, but they are just different. The GPS requires additional equipment and additional information. GPS only works if you have a specific street address. Your friend’s directions indicate that you should leave the hotel and walk five blocks north.
The accuracy of these two strategies depends on whether the city you are in is more like Washington D.C. or Boston. I mention these two cities, because I have lived in both of them, learned how to drive in Washington D.C. and then later lived in Boston for 10 years. Though both cities are amazing in their own right, the roads in D.C. and Boston are laid out quite differently. Washington D.C.’s roads follow a grid with numbered streets running north to south, letter streets running east to west and states running diagonally. Therefore, if the M1 Hotel is on M and 1st street and DLPFC is 5 blocks north, then you can easily find your way to DLPFC by simply walking along 1st street until you get to H street. However, if you are in Boston, where they say the roads were created by paving over cow paths, walking 5 blocks down the windy 1st street will likely never take you in a straight line toward DLPFC. If you want to get from your hotel to DLPFC in Boston, you’re going to need a GPS.
Ok. So back to your brain. Is your brain mapped out like D.C. or Boston? Hard to say without looking at it and Phrenology aside, there is no “depression” spot on the scalp. Every brain is different and none are perfectly predictable. That being said, most are closer to D.C. than Boston. In general, the brain is laid out in a typical pattern. The DLPFC is so named because it is dorsal (on the top) and lateral (on the side) and in the prefrontal (front part) of the brain. It never hurts to use neuronavigation (or GPS in this analogy), but it may not be necessary. That being said, if there is reason to believe that your brain may be wired up differently then you may want to use the “GPS system.” Perhaps you have a developmental disorder, like autism, or you’ve had a brain injury, like a concussion. If this is the case, it is very possible that the region of the brain that may be the optimal TMS therapeutic target for you would not be the same region that would be optimal for others. An individual that may benefit from neuronavigated TMS may be someone who has tried standard (non-neuronavigated) TMS and did not respond. In this case, it is possible that this individual did not respond because the stimulation did not reach the optimal target for them. Maybe that person’s brain is laid out more like Boston!
So you may be asking, “Is there any downside to neuronavigation?” Well, not necessarily a downside, but as I mentioned before only one TMS device company has FDA clearance for neuronavigated rTMS. All other devices use scalp-based targeting. So unless your clinic has a Nexstim NBT system, the addition of a neuronavigation system to a different TMS device would be considered “off-label” and thus likely not covered by insurance. Additionally, neuronavigation requires an MRI. Certain people may not be able to get in an MRI machine (including people with implanted metal in their body (including braces) or those who are severely claustrophobic.
Another question that often comes up is, “Once I have an MRI how does the TMS operator know which is the “correct” spot for me? Is there some brain landmark?” This is the million dollar question. Dysfunction in what part of the brain or what network is underlying depression (or any other condition for that matter)? Is it the same for everyone? The quick answer is we don’t know for sure and yes, there is variability across individuals as to which network may be underlying their specific symptoms. Some believe that the most optimal target is the region of DLPFC that is anticorrelated (or the most negatively correlated) with a region of the brain called the subgenual cingulate. But you need a special type of MRI to get this information (a resting-state functional connectivity MRI) that is not typically used for clinically available (even neuronavigated) TMS. Others believe that there are “biotypes” with some people responding best to one target and others responding best to completely different targets (even sometimes outside of DLPFC).
We still have a ways to go in optimizing TMS for each individual brain. The good news is we have the tools and technology. We know more about the brain and how it functions and have advanced neuroimaging technology capable of creating high-resolution structural and functional images. There are also hundreds of researchers working in the brain stimulation field including Engineers, Psychiatrists, Neuroscientists, Psychologists and Neurologists. And I will continue to share with you all what my colleagues and I learn about TMS protocols and bring you the most cutting-edge research as soon as it is available.