Research Idea: TMS Sonar

TMS ‘Sonar’ for mapping brain region activity coupling

Modern neuroscience is increasingly suggesting that a great deal of a person’s personality, pathology, and cognitive approach is encoded into which of their brain regions are activity-coupled together. That is to say, which of someone’s brain regions are more vs. less wired together, compared to some baseline, determines much about that person.

Right now such coupling is largely invisible and unquantifiable. If we are to move toward a clearer understanding of individual differences, not to mention psychiatric conditions, it would be invaluable to have a test for this activity coupling. A combination TMS+fMRI alternated pulse device- as it could stimulate a specific brain region/network, and measure how it affected the activity in other regions- may very well provide an objective basis for psychiatric diagnosis and treatment recommendations, and perhaps even a firmer foundation for psychology as a whole.

The following is a somewhat technical writeup of the idea. Not into detailed neuroscience stuff? Click here.

Technology:

A Transcranial Magnetic Stimulation (TMS) device able to perform precisely targeted regional stimulation paired with a functional Magnetic Resonance Imaging (fMRI) device, calibrated such that one will be active while the other is dormant, and able to toggle swiftly between the two. Stimulate one brain region (TMS), then observe which other regions light up (fMRI).

TMS devices function by lowering neuron activation thresholds by rapidly oscillating a magnetic field through the target area. They are commonly found in research institutions and are used for both research into brain region function (e.g., disable the function of a specific brain region by overstimulating it via TMS, and observe which cognitive functions are and are not affected), and in treatment for depression.

fMRI devices function by using the proxies of bloodflow and oxygenation to measure regional brain activity. More active regions need more bloodflow to function, and this increased level can be measured via applying a magnetic pulse and measuring the changes in local magnetic permeability.

Existing approaches:

Brain scanning techniques: Most current types of brain scans are ill-suited to gathering regional activity data, as they either tend to focus on physical neuroanatomy (CAT, MRI) or involve poor spacial resolution (PET, EEG, MEG). fMRI is currently the tool of choice for looking at brain region activity, and researchers have used it to look into whether, how, and why brain regions may be linked, and how variations in these linkages may affect cognition. However, the passive nature of fMRI complicates drawing any firm conclusions about the causality involved: e.g., one might show subjects pictures of spiders, or naked women, or christmas presents, and record their fMRI response, but what is really being measured? Are the results clear, reproduceable, and useful, e.g., enough such that they could form the basis of a diagnosis or treatment recommendation? Very often not. On the other hand, TMS Sonar bypasses the ambiguity involved in trying to induce a standardized abstract processing state and instead tests for objective, content-neutral activity coupling between brain regions, something fMRI cannot. In short- TMS Sonar could tell us new and interesting things about regional dynamics that fMRI alone will never be able to.

Personality questionares: There are a plethora of personality tests: the MMPI, Myers-Briggs, Big 5, and so on. However, psychologists tend to be the first to list the limits of these tests. E.g., they rely on a subject to truthfully and accurately answer what are ultimately subjective and relative questions, and they focus more on what can be measured than deeper brain dynamics that, as Plato would say, “carve nature at its joints.” TMS Sonar could be objective and illuminating in ways that questionares will never be.

This approach in a nutshell:

Systematically ‘ping’ different brain regions with TMS and map which other regions light up via fMRI.

Types of data this could gather:

This device seems promising for exploring at least two different neural phenomena at the macro level: linkages and leakages.

Linkages:

An important part of how the brain works is the layout of which regions of tissue become activity-coupled. There seems to be significant natural variation in this, and it also seems to lie at the center of many sorts of brain disorders: i.e., a region should be strongly activity-coupled to a nearby region yet isn’t, or is activity-coupled to a region it shouldn’t be. These abnormal coupling patterns are for the most part currently invisible to us, but would likely show up under TMS Sonar.

Two particularly good examples of cases where TMS sonar could add to our existing analysis would be in PTSD and Depression, where the causal core may involve certain regions of the brain undergoing abnormal activity linkages or delinkages. Specifically, not only will many types of Depression likely center around activity coupling problems, but presumably different types of depression will have different and indicative activity coupling signatures, which can then inform more specific treatment recommendations.

The general hypothesis here is that activity linkages between brain regions vary considerably between people, and this will always have functional implications. Presumably these activity linkages will often correlate to a fair degree with interesting macro-level conditions, including some forms of psychopathology, and may be useful when diagnosing and designing individual treatments.

Leakages:

The other key use of this technology would be to identify and map microstructural variation as it pertains to information movement in the brain: i.e., how much information ‘leaks’ between different brain regions. Preliminary data indicates this varies across individuals and is implicated in certain types of pathology, and may inform larger, non-pathological differences in cognition.

A focal point for thinking about this issue is synesthesia. Examples of synesthesia include seeing numbers as inherently colored, or experiencing sounds in response to motion, in an automatic, involuntary way. It’s thought that this emerges from deficits in neural pruning between functional brain regions leading to cross-talk between them, and we know this condition manifests itself through sensory perception in roughly 1 out of every 23 people. However, it’s quite possible that this figure underestimates the prevalence and cognitive significance of synesthesia, since when synesthesia exists between two non-sensory regions of the brain there will likely be no consistent indicative symptoms (though it may still play a significant role in cognitive function). A pulse scanning method such as TMS sonar could likely map synesthesia across the entire brain.

The general hypothesis here is that everyone has a little bit of synesthesia, and a method to map individuals in terms of how much and which regions are affected could lead to great leaps in understanding certain forms of psychopathology and individual differences.

Hurdles:

– TMS is generally used to disrupt a brain region’s function by overloading it. The assumption that is made here is that either

1. a sufficiently low dose of TMS can be found to still effectively stimulate regional activity without disrupting regional function; or,

2. stimulation via TMS, though it may disrupt regional function, will still be an effective trigger for a representative sampling of activity coupling.

In other words, will TMS, as a general regional stimulation, evoke a coherent-enough activity response so as to be indicative of functional linkages?

3. fMRI doesn’t have great temporal resolution. I’m not certain this would matter for the purposes it’s being used, and the tech is constantly improving, but it’s a potential caveat.

– Though both of these devices are currently in use, there may be engineering challenges in creating equipment that can handle both TMS and fMRI in rapid succession, particularly since they both use magnetic pulses in the course of their operation. The solution to this may involve some temporal latency in the fMRI measurement.

 

Why stop at measurement? The case for using this to cure diseases:

If abnormal BRACs were found in someone suffering from a serious disorder, presumably we could use a TMS conditioning treatment to alter these to a known-healthy baseline by activation condition via TMS pulses (brain regions that fire together, wire together?). If pathology is caused by abnormal BRACs, presumably this could cure them (with a particular emphasis on very destructive disorders where therapy and drugs have failed). An option of last resort, perhaps, but an option nonetheless.

Discussion/Open Questions:

– This idea has a lot in common with Giulio Tononi’s approach for analyzing coma patients: stimulate their brains with TMS, and see how long it takes for the ‘ringing’ to die down. If it takes a while (like it does in normal people), they probably still have their higher cognitive functions intact. If it doesn’t, they’re probably vegetables.

– What constitutes a ‘brain region’? I have in mind something akin to a Brodmann area, though I’m not married to that specific organizational system.

– What would this process feel like?

– Could sonic stimulation work better than TMS in some cases?

– How close is this sort of evoked Brain Region Activity Coupling (BRAC) to how BRAC works ‘in the wild’? Relatedly, how contextual is BRAC: do which regions are coupled together change significantly when one is in different moods, or will there be significant-enough commonalities such that this usually won’t be a problem in diagnosis?

– What are the underlying causes of BRAC? Relatedly, how plastic is it?

– Could this type of challenge-response hybrid be able to measure such things as relative dominance between brain regions, or a particularly high or low tendency for a region to fall into a coherent pattern given stimulation? What would the likely functional/psychological implications of this data be?

– It’s really unknown how central BRAC is in neural function. There’s not a lot of data out there because we can’t currently measure it with any degree of rigor or precision. Straight-up differential regional activity appears very important right now– but it’s difficult to see how it wouldn’t appear important for brain dynamics, as we model things based on what we can measure, and that’s one of the few functional measurable attributes.

– Could we compare evoked BRAC with coupling topologies derived from connectomes and diffusion-weighted fMRI?