Functional Connectivity Between Surgically Disconnected Brain Regions?

By Neuroskeptic | April 21, 2017 2:26 pm

A new article posted on preprint site bioRxiv has generated a lot of interest among neuroscientists on Twitter. The article reports the existence of ‘functional connectivity‘ between surgically disconnected distant brain regions using fMRI, something that in theory shouldn’t be possible.

This is big news, if true, because it suggests that fMRI functional connectivity isn’t entirely a reflection of actual signalling between brain areas. Rather, something else must be able to produce connectivity – most likely it has to do with the constriction of blood vessels in the brain. Whatever the source of the non-neuronal connectivity is, it raises the worrying possibility that it might be contaminating fMRI studies.

The research comes from a University of Iowa team, with the first author being David E. Warren.

Warren et al. studied 5 patients who’d had surgery to disconnect one of their temporal poles, for epilepsy treatment. Here’s the resting state fMRI connectivity of the disconnected temporal pole (seed-voxel) within each subject, compared to the pattern of connectivity in healthy subjects with the same temporal pole seed.


In a nutshell, the results shows that in each of the five subjects, there were areas which were significantly “connected” to the disconnected temporal pole. Different brain areas were involved in different subjects, and the connectivity was relatively weak, with most blobs only appearing at the Z>2.33 cluster defining threshold and not the more robust Z>3.1 threshold.

Warren et al. conclude that their results cast doubt on the nature of fMRI connectivity:

Our findings have significant implications for studies using functional connectivity measures because – for the first time – we show that a brain region confirmed to have no structural neural connections can show reliable functional connectivity with remote brain regions. These results challenge a key premise in the field: that functional connectivity reflects mono- or polysynaptic communication along structural pathways.

In my view, this is a very nice piece of work, but the results are a little hard to interpret. Using surgical disconnection patients to study fMRI connectivity is a brilliant idea. However, the connectivity between disconnected areas was not very strong and, as it was variable, I suspect that it wouldn’t appear at all in a group-based analysis.

In other words, I’m convinced that Warren et al. have shown the existence of non-neuronal connectivity, but I’m less sure that it’s strong enough to have a major impact on the average fMRI study, although we certainly can’t rule it out.

There are some methodological questions. Warren et al. did not record measures of pulse and breathing from their participants. These variables, often referred to as physiological parameters, are commonly collected and used in fMRI connectivity analyses to control for the effects of blood pumping and the breath cycle which can cause various changes across the brain.

Warren et al. acknowledge that the lack of physiological measures is a limitation of their study; they note that “many neuroimaging studies” don’t include such measures, but it’s fair to say that many studies do, so ideally this one would have. As it stands, it’s unclear whether the non-neuronal connectivity seen in this study would be removed by controlling for physiological parameters.

A few other methods points were raised in a comment here.

Overall, this article should serve as a prompt for more work in this area, but I wouldn’t say it’s ‘doomsday’ for fMRI connectivity just yet.

CATEGORIZED UNDER: fMRI, methods, select, Top Posts
  • Marc Dion

    tuning forks are not physically connected and yet both can simultaneously resonate with a signal passing through the air. Brain waves don’t require any physical medium, they are electro-magnetic. Those EM signals can be generated by one component of the brain and be induced into another component of the brain by resonance.

  • CLS

    The existence of correlations due to structured noise (motion, physiological, scanner artefacts) in fMRI is well known. Reported correlations are small and also do not resemble classical connectivity patterns but rather “noise regions” (white matter, outline of the ventricles). This is consistent with small noise correlations. The design of the study is beautiful, but I don’t see anything really new or worrisome in those results.

  • daniele marinazzo

    I definitely think that if there is someone still really thinking (or selling the idea) that “functional connectivity”, in particular intended as a correlation, is purely neural in fMRI, then this study could be helpful.
    On the other hand “functional connectivity” has been defined exactly as a complement to “structural connectivity”. Whenever we correlate brain activation to behavior, or even earth temperature with carbon dioxide emissions, we’re perfectly fine with not having a direct structural pathway.
    Of course we need to consider all the possible physiological variables, the movement etc, in the same way in which we must be careful in our statistical methods, but observing statistical dependencies between parts of a system, structurally connected or not, and interpreting their modulations, can still be extremely instructive.
    All of this in general. When it comes to this particular study, I think that in a group study these correlations would not have survived, and that many other studies can be conducted placing seeds in the white matter or in the skull. But again, if we are not biased or hypocrites in the interpretation, and if the methods are solid, we should just be happy with any result, confident that we have learned something.

  • OWilson

    Organs can “live” sans body and brain, so could the phenomena be related to vestigial activity.

    For example a bee’s stinger continues to pulse and further insert itself into the victim long after it has been ripped from the bee’s body.

    There does not have to be Einstein’s, “spooky action at a distance” to explain it.

  • djlewis

    The term “functional connectivity” has always been somewhat of a scam,
    meant to imply that there is structural connectivity despite lack of
    evidence for that. Current (or foreseeable) technology is simply unable
    to measure structural connectivity on any but the most primitive level,
    and that mostly in animals. So someone (who was it?) came up with the
    clever ploy to rename what is actually synchronization.

    But now it appears
    that neuroscientists have been fooled by their own scam into thinking
    that synchronization actually entails structural connection. Or maybe
    they are just shocked, shocked to find the truth!

    And by the way, there’s nothing more wrong with studying synchronization of brain blobs apart from actual neural activity than there is in unsynchronized fMRI. The former is just second-order statistical pattern detection and correlation, a natural progression from the original first-order patterns.

    But let’s be clear — it’s ALL about statistical activity patterns of proxy phenomena, not neural activity per se, abut which we have only the faintest and most rudimentary knowledge, and that (again) from animal and lesion studies and the extremely rare cases where limited neurosurgical experiments on humans are ethically feasible.

    • OWilson

      We must live with the simple fact of life, that the intellectual fields least understood, have the most zealous theorists.

      Psychology, Psychiatry, Anthropology, Climate “science”, Archaeology and yes, Neuroscience, can all be shaped into a social or political narrative, convenient to the current conventional wisdom. :)

  • DS

    There is zero reason to rule out subject motion as the cause of the correlations. None of the methods used in the paper have been shown to remove all significant correlations due to motion. Saying we did our best and thinking wishfully with respect to the efficacy of the applied motion correction methods may fool foolish prepublication reviewers with a vested interest in these methods but it doesn’t fool post-publication reviewers.

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  • Hailey Politte

    This study definitely needs more background and research to further explain the possibilities and the how’s and why’s. However, this is a huge finding considering scientist have found and proved that neurons, whose sole function is relaying information, are really the root to our body’s responses. Is there a way we could change the way part of the brain functions with non-neuronal connectivity? Is there a different way or signals that can be put into place of neuron activity? I am curious how there is “function” or is still considered active, whether it be communication with another part of the brain or body or just simply showing sedentary involvement with just itself. Obviously each part of the brain is responsible for different functions, so if there was a possible way to connect “disconnected” lobes, the stimulant, or what reconnects the two lobes’ activity, would vary in response. This is very intriguing information, and I hope the findings lead to exponential growth in the neuroscience field.

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About Neuroskeptic

Neuroskeptic is a British neuroscientist who takes a skeptical look at his own field, and beyond. His blog offers a look at the latest developments in neuroscience, psychiatry and psychology through a critical lens.


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