Insula and Anterior Cingulate: the ‘everything’ network or systemic neurovascular confound?

February 18th, 2012 § 12 Comments

It’s no secret in cognitive neuroscience that some brain regions garner more attention than others. Particularly in fMRI research, we’re all too familiar with certain regions that seem to pop up in study after study, regardless of experimental paradigm. When it comes to areas like the anterior cingulate cortex (ACC) and insula (AIC), the trend is obvious. Generally when I see the same brain region involved in a wide a variety of tasks, I think there must be some very general level function which encompasses these paradigms. Off the top of my head, the ACC and AIC are major players in cognitive control, pain, emotion, consciousness, salience, working memory, decision making, and interoception to name a few. Maybe on a bad day I’ll look at a list like that and think, well localization is just all wrong, and really what we have is a big fat prefrontal cortex doing everything in conjunction. A paper published yesterday in Cerebral Cortex took my breath away and lead to a third, more sinister option: a serious methodological confound in a large majority of published fMRI papers.

Neurovascular coupling and the BOLD signal: a match not made in heaven

An important line of research in neuroimaging focuses on noise in fMRI signals. The essential problem of fMRI is that, while it provides decent spatial resolution, the data is acquired slowly and indirectly via the blood-oxygenation level dependent (BOLD) signal. The BOLD signal is messy, slow, and extremely complex in its origins. Although we typically assume increasing BOLD signal equals greater neural activity, the details of just what kind of activity (e.g. excitatory vs inhibitory, post-synaptic vs local field) are murky at best. Advancements in multi-modal and optogenetic imaging hold a great deal of promise regarding the signal’s true nature, but sadly we are currently at a “best guess” level of understanding. This weakness means that without careful experimental design, it can be difficult to rule out non-neural contributors to our fMRI signal. Setting aside the worry about what neural activity IS measured by BOLD signal, there is still the very real threat of non-neural sources like respiration and cardiovascular function confounding the final result. This is a whole field of research in itself, and is far too complex to summarize here in its entirety. The basic issue is quite simple though.

End-tidal C02, respiration, and the BOLD Signal

In a nutshell, the BOLD signal is thought to measure downstream changes in cerebral blood-flow (CBF) in response to neural activity. This relationship, between neural firing and blood flow, is called neurovascular coupling and is extremely complex, involving astrocytes and multiple chemical pathways. Additionally, it’s quite slow: typically one observes a 3-5 second delay between stimulation and BOLD response. This creates our first noise-related issue; the time between each ‘slice’ of the brain, or repetition time (TR), must be optimized to detect signals at this frequency. This means we sample from our participant’s brain slowly. Typically we sample every 3-5 seconds and construct our paradigms in ways that respect the natural time lag of the BOLD signal. Stimulate too fast, and the vasculature doesn’t have time to respond. Stimulation frequency also helps prevent our first simple confound: our pulse and respiration rates tend oscillate at slightly slower frequencies (approximately every 10-15 seconds). This is a good thing, and it means that so long as your design is well controlled (i.e. your events are properly staggered and your baseline is well defined) you shouldn’t have to worry too much about confounds. But that’s our first problematic assumption; consider for example when one’s paradigms use long blocks of obscure things like “decide how much you identify with these stimuli”. If cognitive load differs between conditions, or your groups (for example, a PTSD and a control group) react differently to the stimuli, respiration and pulse rates might easily begin to overlap your sampling frequency, confounding the BOLD signal.

But you say, my experiment is well controlled, and there’s no way my groups are breathing THAT differently! Fair enough, but this leads us to our next problem: end tidal CO2. Without getting into the complex physiology, end-tidal CO2 is a by-product of respiration. When you hold your breath, CO2 blood levels rise dramatically. CO2 is a potent vasodilator, meaning it opens blood vessels and increases local blood flow. You’ve probably guessed where I’m going with this: hold your breath in the fMRI and you get massive alterations in the BOLD signal. Your participants don’t even need to match the sampling frequency of the paradigm to confound the BOLD; they simply need to breath at slightly different rates in each group or condition and suddenly your results are full of CO2 driven false positives! This is a serious problem for any kind of unconstrained experimental design, especially those involving poorly conceptualized social tasks or long periods of free activity. Imagine now that certain regions of the brain might respond differently to levels of CO2.

This image is from Change & Glover’s paper, “Relationship between respiration, end-tidal CO2, and BOLD signals in resting-state fMRI”. Here they measure both CO2 and respiration frequency during a standard resting-state scan. The image displays the results of group-level regression of these signals with BOLD. I’ve added circles in blue around the areas that respond the strongest. Without consulting an atlas, we can clearly see that bilateral anterior insula extending upwards into parietal cortex, anterior cingulate, and medial-prefrontal regions are hugely susceptible to respiration and CO2. This is pretty damning for resting-state fMRI, and makes sense given that resting state fluctuations occur at roughly the same rate as respiration. But what about well-controlled event related designs? Might variability in neurovascular coupling cause a similar pattern of response? Here is where Di et al’s paper lends a somewhat terrifying result:


Di et al recently investigated the role of vascular confounds in fMRI by administrating a common digit-symbol substitution task (DSST), a resting state, and a breath-holding paradigm. Signals related to resting-state and breath-holding were then extracted and entered into multiple regression with the DSST-related activations. This allowed Di et al to estimate what brain regions were most influenced by low-frequency fluctuation (ALFF, a common resting state measure) and purely vascular sources (breath-holding). From the figure above, you can see that regions marked with the blue arrow were the most suppressed, meaning the signal explained by the event-related model was significantly correlated with the covariates, and in red where the signal was significantly improved by removal of the covariates. The authors conclude that “(results) indicated that the adjustment tended to suppress activation in regions that were near vessels such as midline cingulate gyrus, bilateral anterior insula, and posterior cerebellum.” It seems that indeed, our old friends the anterior insula and cingulate cortex are extremely susceptible to neurovascular confound.

What does this mean for cognitive neuroscience? For one, it should be clear that even well-controlled fMRI designs can exhibit such confounds. This doesn’t mean we should throw the baby out with the bathwater though; some designs are better than others. Thankfully it’s pretty easy to measure respiration with most scanners, and so it is probably a good idea at minimum to check if one’s experimental conditions do indeed create differential respiration patterns. Further, we need to be especially cautious in cases like meditation or clinical fMRI, where special participant groups may have different baseline respiration rates or stronger parasympathetic responses to stimuli. Sadly, I’m afraid that looking back, these findings greatly limit our conclusions in any design that did not control for these issues. Remember that the insula and ACC are currently cognitive neuroscience’s hottest regions. I’m not even going to get into resting state, where these problems are all magnified 10 fold. I’ll leave you with this image from neuroskeptic, estimating the year’s most popular brain regions:

Are those spikes publication fads, every-task regions, or neurovascular artifacts? You be the judge.

 
edit:As many of you had questions or comments regarding the best way to deal with respiratory related issues, I spoke briefly with resident noise expert Torben Lund at yesterday’s lab meeting. Removal of respiratory noise is fairly simple, but the real problem is with end-tidal C02. According to Torben, most noise experts agree that regression techniques only partially remove the artifact, and that an unknown amount is left behind even following signal regression. This may be due to slow vascular saturation effects that build up and remain irrespective of shear breath frequency. A very tricky problem indeed, and certainly worth researching.
 
 
Note: credit goes to my methods teacher and fMRI noise expert Torben Lund, and CFIN neurobiologist Rasmus Aamand, for introducing and explaining the basis of the C02/respiration issue to me. Rasmus particularly, whose sharp comments lead to my including respiration and pulse measures in my last meditation project.

Neuroscientists: What’s the most interesting question right now?

February 14th, 2012 § 10 Comments

After 20 years of cognitive neuroscience, I sometimes feel frustrated by how little progress we’ve made. We still struggle with basic issues, like how to ask a subject if he’s in pain, or what exactly our multi-million dollar scanners measure. We lack a unifying theory linking information, psychological function, and neuroscientific measurement. We still publish all kinds of voodoo correlations, uncorrected p-values, and poorly operationalized blobfests. Yet, we’ve also laid some of the most important foundational research of our time. In twenty years we’ve mapped a mind boggling array of cognitive function. Some of these attempts at localization may not hold; others may be built on shaky functional definitions or downright poor methods. Even in the face of this uncertainty, the shear number and variety of functions that have been mapped is inspiring. Further, we’ve developed analytic tools to pave the way for an exciting new decade of multi-modal and connectomic research. Developments like resting-state fMRI, optogenetics, real time fMRI, and multi-modal imaging, make for a very exciting time to be a Cognitive Neuroscientist!

Online, things can seem a bit more pessimistic. Snarky methods blogs dedicated to revealing the worst in field tend to do well, and nearly any social-media savy neurogeek will lament the depressing state of science journalism and the brain. While I am also tired of incessantly phrenological, blob-obsessed reports (“research finds god spot in the brain, are your children safe??”) I think we share some of the blame for not communicating properly about what interests and challenges us. For me, some of the most exciting areas of research are those concerning getting straight about what our measurements mean- see the debates over noise in resting state or the neural underpinnings of the BOLD signal for example. Yet these issues are often reported as dry methodological reports, the writers themselves seemingly bored with the topic.

We need to do a better job illustrating to people just how complex and infantile our field is. The big, sexy issues are methodological in nature. They’re also phenomenological in nature. Right now neuroscience is struggling to define itself, unsure if we should be asking our subjects how they feel or anesthetizing them. I believe that if we can illustrate just how tenuous much of our research is, including the really nagging problems, the public will better appreciate seemingly nuanced issues like rest-stimulus interaction and noise-regression.

With that in mind- what are your most exciting questions, right now? What nagging thorn ails you at all steps in your research?

For me, the most interesting and nagging question is, what do people do when we ask them to do nothing? I’m talking about rest-stimulus interaction and mind wandering. There seem to be two prevailing (pro-resting state) views: that default mode network-related activity is related to subjective mind-wandering, and/or that it’s a form of global, integrative, stimulus independent neural variability. On the first view, variability in participants ability to remain on-task drive slow alterations in behavior and stimulus-evoked brain activity. On the other, innate and spontaneous rhythms synchronize large brain networks in ways that alter stimulus processing and enable memory formation. Either way, we’re left with the idea that a large portion of our supposedly well-controlled, stimulus-related brain activity is in fact predicted by uncontrolled intrinsic brain activity. Perhaps even defined by it! When you consider that all this is contingent on the intrinsic activity being real brain activity and not some kind of vascular or astrocyte-driven artifact, every research paradigm becomes a question of rest-stimulus interaction!

So neuroscientists, what keeps you up at night?

A brave new default mode in meditation practitioners- or just confused controls? Review of Brewer (2011)

February 8th, 2012 § 3 Comments

Given that my own work focuses on cognitive control, intrinsic connectivity, and mental-training (e.g. meditation) I was pretty excited to see Brewer et al’s paper on just these topics appear in PNAS just in time for the winter holidays. I meant to review it straight away but have been buried under my own data analysis until recently. Sadly, when I finally got around to delving into it, my overall reaction was lukewarm at best. Without further ado, my review of:

“Meditation experience is associated with differences in default mode network activity and connectivity

Abstract:

“Many philosophical and contemplative traditions teach that “living in the moment” increases happiness. However, the default mode of humans appears to be that of mind-wandering, which correlates with unhappiness, and with activation in a network of brain areas associated with self-referential processing. We investigated brain activity in experienced meditators and matched meditation-naive controls as they performed several different meditations (Concentration, Loving-Kindness, Choiceless Awareness). We found that the main nodes of the default mode network(medial prefrontal and posterior cingulate cortices) were relatively deactivated in experienced meditators across all meditation types. Furthermore, functional connectivity analysis revealed stronger coupling in experienced meditators between the posterior cingulate, dorsal anterior cingulate, and dorsolateral prefrontal cortices (regions previously implicated in self- monitoring and cognitive control), both at baseline and during meditation. Our findings demonstrate differences in the default-mode network that are consistent with decreased mind-wandering. As such, these provide a unique understanding of possible neural mechanisms of meditation.”

Summary:

Aims: 9/10

Methods: 5/10

Interpretation: 7/10

Importance/Generalizability: 4/10

Overall: 6.25/10

The good: simple, clear cut design, low amount of voodoo, relatively sensible findings

The bad: lack of behavioral co-variates to explain neural data, yet another cross-sectional design

The ugly: prominent reporting of uncorrected findings, comparison of meditation-naive controls to practitioners using meditation instructions (failure to control task demands).

Take-home: Some interesting conclusions, from a somewhat tired and inconclusive design. Poor construction of baseline condition leads to a shot-gun spattering of brain regions with a few that seem interesting given prior work. Let’s move beyond poorly controlled cross-sections and start unravelling the core mechanisms (if any) involved in mindfulness.

Extended Review:
Although this paper used typical GLM and functional connectivity analyses, it loses points in several areas. First, although the authors repeatedly suggest that their “relative paucity of findings” may be “driven by the sensitivity of GLM analysis to fluctuations at baseline… and since meditation practitioners may be (meditating) at baseline…” the contrast would be weak. However, I will side with Jensen et al (2011) here in saying: Meditation naive controls receiving less than 5 minutes of instruction in “focused attention, loving-kindness and choiceless awareness” are simply no controls at all. The argument that the inability of the GLM to detect differences that are quite obviously confounded by a lack of an appropriately controlled baseline is galling at best. This is why we use a GLM-approach; it’s senseless to make conclusions about brain activity when your baseline is no baseline at all. Telling meditation-naive controls to utilize esoteric cultural practices of which they have only just been introduced too, and then comparing that to highly experienced practitioners is a perfect storm of cognitive confusion and poorly controlled demand characteristic. Further, I am disappointed in the review process that allowed the following statement “We found a similar pattern in the medial prefrontal cortex (mPFC), another primary node of the DMN, although it did not survive whole-brain correction for signifigance” followed by this image:

image

These results are then referred to repeatedly in the following discussion. I’m sorry, but when did uncorrected findings suddenly become interpretable? I blame the reviewers here over the authors- they should have known better. The MPFC did not survive correction and hence should not be included in anything other than a explicitly stated as such “exploratory analysis”. In fact it’s totally unclear from the methods section of this paper how these findings where at all discovered: did the authors first examine the uncorrected maps and then re-analyze them using the FWE correction? Or did they reduce their threshold in an exploratory post-hoc fashion? These things make a difference and I’m appalled that the reviewers let the article go to print as it is, when figure 1 and the discussion clearly give the non-fMRI savy reader the impression that a main finding of this study is MPFC activation during meditation. Can we please all agree to stop reporting uncorrected p-values?

I will give the authors this much; the descriptions of practice, and the theoretical guideposts are all quite coherent and well put-together. I found their discussion of possible mechanisms of DMN alteration in meditation to be intriguing, even if I do not agree with their conclusion. Still, it pains me to see a paper with so much potential fail to address the pitfalls in meditation research that should now be well known. Indeed the authors themselves make much ado about how difficult proper controls are, yet seem somehow oblivious to the poorly controlled design they here report. This leads me to my own reinterpretation of their data.

A new default mode, or confused controls?

Brewer et al (2011) report that, when using a verbally guided meditation instruction with meditation naive-controls and experienced practitioners, greater activations in PCC, temporal regions, and for loving-kindness, amygdala are found. Given strong evidence by colleagues Christian Jensen et al (2011) that these kinds of contrasts better represent differences in attentional effort than any mechanism inherent to meditation, I can’t help but wonder if what were seeing here is simply some controls trying to follow esoteric instructions and getting confused in the process. Consider the instruction for the choiceless awareness condition:

“Please pay attention to whatever comes into your awareness, whether it is a thought, emotion, or body sensation. Just follow it until something else comes into your awareness, not trying to hold onto it or change it in any way. When something else comes into your awareness, just pay attention to it until the next thing comes along”

Given that in most contemplative traditions, choiceless awareness techniques are typically late-level advanced practices, in which the very concept of grasping to a stimulus is distinctly altered and laden with an often spiritual meaning, it seems obvious to me that such an instruction constitutes and excellent mindwandering inducement for naive-controls. Do you meditate? I do a little, and yet I find these instructions extremely difficult to follow without essentially sending my mind in a thousand directions. Am I doing this correctly?  When should I shift? Is this a thought or am I just feeling hungry? These things constitute mind-wandering but for the controls, I would argue they constitute following the instructions. The point is that you simply can’t make meaningful conclusions about the neural mechanisms involved in mindfulness from these kinds of instructions.

Finally, let’s examine the functional-connectivity analysis. To be honest, there isn’t a whole lot to report here; the functional connectivity during meditation is perhaps confounded by the same issues I list above, which seems to me a probable cause for the diverse spread of regions reported between controls and meditators. I did find this bit to be interesting:

“Using the mPFC as the seed region, we found increased connectivity with the fusiform gyrus, inferior temporal and parahippocampal gyri, and left posterior insula (among other regions) in meditators relative to controls during meditation (Fig. 3, Fig. S1H, and Table S3). A subset of those regions showed the same relatively increased connectivity in meditators during the baseline period as well (Fig. S1G and Table1)

I found it interesting that the meditation conditions appear to co-activate MPFC and insula, and would love to see this finding replicated in properly controlled design. I also have a nagging wonder as to why the authors didn’t bother to conduct a second-level covariance analysis of their findings with the self-reported mind-wandering scores. If these findings accurately reflect meditation-induced alterations in the DMN, or as the authors more brazenly suggest “a entirely new default network”, wouldn’t we expect their PCC modulations to be predicted by individual variability in mind-wandering self-reports? Of course, we could open the whole can of worms that is “what does it mean when you ask participants if they ‘experienced mind wandering” but I’ll leave that for a future review. At least the authors throw a bone to neurophenomenology, suggesting in the discussion that future work utilize first-person methodology. Indeed.

Last, it occurs to me that the primary finding, of increased DLPFC and ACC in meditation>Controls, also fits well with my intepretation that this design is confounded by demand characteristics. If you take a naive subject and put them in the scanner with these instructions, I’ve argued that their probably going to do something a whole lot like mind-wandering. On the other hand, an experienced practitioner has a whole lot of implicit pressure on them to live up to their tradition. They know what they are their for, and hence they know that they should be doing their thing with as much effort as possible. So what does the contrast meditation>naive really give us? It gives us mind-wandering in the naive group, and increased attentional effort in the practitioner group. We can’t conclude anything from this design regarding mechanisms intrinsic to mindfulness; I predict that if you constructed a similar setting with any kind of dedicated specialist, and gave instructions like “think about your profession, what it means to you, remember a time you did really well” you would see the exact same kind of results. You just can’t compare the uncomparable.

Disclaimer: as usual, I review in the name of science, and thank the authors whole-heartily for the great effort and attention to detail that goes into these projects.  Also it’s worth mentioning that my own research focuses on many of these exact issues in mental training research, and hence i’m probably a bit biased in what I view as important issues.

Coming back from a long hiatus in blogging

February 4th, 2012 § Leave a Comment

Image

I’ve been crazy busy the past year, primarily mastering Matlab and fMRI statistics. It’s been  a good run and I’ve both collected and analyzed a ton of data. In just a little over a year, I’ve completed a longitudinal study of meditation, including two event-related paradigms, resting-state, DTI, high-resolution T1 anatomical data, and a bevy of physiological and behavioral data. On top of that, I collected a similarly broad dataset for my Varela-award study “The Neurophenomenology of Mindfulness: Meta-cognitive Awareness in Adept Contemplatives”. Finally I’ve written and published a first attempt at a broad-based model of social-cognitive action control, the “Pre-loading Model”.

It’s been a pretty intense year, but I’m excited to write-up and publish my results and you can be sure that I’ll be sharing them here first. I look forward to discussing some of the more intriguing bits, and am also excited by the specter of what looks like a fascinating post-doctoral project.

When I look back I can’t believe everything I’ve learned in the year gone. It feels like every inch of my gray matter has been packed with vital information regarding BOLD timeseries and their statistical analysis. Finally sitting down to write something other than code feels great; I can’t believe the way my perspectives and research interests have changed in absorbing all this new knowledge.

As I move from analyzing my data to writing it up, I hope to return to regular blogging, as I believe this is the best place to vent and develop my ideas, in a living and shared format. I’m not sure exactly what direction i’ll take Neuroconscience in the months to come, but I hope to be able to have fun sharing my ideas and experiences with the community.

Forthcoming: this is your brain on WoW

July 26th, 2011 § Leave a Comment

Thanks to philosopher and cognitive scientist Evan Thompson for sharing a project that was accepted today in Cerebral Cortex. I’m sure we can expect to see this one get reported all over as soon as the actual article is released (i’m looking at you Wired).

Here’s the abstract, via Evan Thompson

“How the human brain goes virtual: distinct cortical regions of the person processing-network are involved in self-identification with virtual avatars.”

Cerebral Cortex: Shanti Ganesh, Hein T. van Schie, Floris P. de Lange, Evan Thompson, and Daniel H.J. Wigboldus

“We applied functional neuroimaging to 22 long-term online gamers and 21 non-gaming controls, while they rated personality traits of self, avatar and familiar others. Strikingly, neuroimaging data revealed greater avatar-referential cortical activity in the left inferior parietal lobe, a region associated with self-identification from a third-person perspective. The magnitude of this brain activity correlated positively with the propensity to incorporate external body enhancements into one’s bodily identity. Avatar-referencing furthermore recruited greater activity in the rostral anterior cingulate gyrus, suggesting relatively greater emotional self-involvement with one’s avatar. Post-scanning behavioral data revealed superior recognition memory for avatar relative to others. Interestingly, memory for avatar positively co-varied with play duration.”

I’ll admit, I expected the usual “self x vs other x produces greater MPFC activity”. These findings are a nice extension to similiar work by Schilbach et al. I find it particularly interesting that the avatar-related activity correlated with a tendency to couple with external tools; a bit of an Andy Clark-esque vibe there. I look forward to reading the full article (and watching the media go nuts)!

Video: Infancy Studies at Rutgers

July 20th, 2011 § Leave a Comment

As someone with a long time fascination with developmental research, particularly in the cognitive neurosciences, I found this short clip totally fascinating.

I can’t imagine the extreme patience that goes into these studies! I’d love to hear more about how researchers in this area control for motion artifacts and other noise-elements. The entire data collection processes is really interesting- do let me know if you have any insight! You can read more about this research here:

http://www.scientificamerican.com/article.cfm?id=how-to-build-a-better-learner

New Meditation Study in Neuroimage: “Meditation training increases brain efficiency in an attention task”

July 11th, 2011 § 7 Comments

Just a quick post to give my review of the latest addition to imaging and mindfulness research. A new article by Kozasa et al, slated to appear in Neuroimage, investigates the neural correlates of attention processing in a standard color-word stroop task. A quick overview of the article reveals it is all quite standard; two groups matched for age, gender, and years of education are administered a standard RT-based (i.e. speeded) fMRI paradigm. One group has an average of 9 years “meditation experience” which is described as “a variety of OM (open monitoring) or FA (focused attention) practices such as “zazen”, mantra meditation, mindfulness of breathing, among others”. We’ll delve into why this description should give us pause for thought in a moment, for now let’s look at the results.

Amplitude of bold responses in the lentiform nucleus, medial frontal gyrus, middle temporal gyrus and precentral gyrus during the incongruent and congruent conditions in meditators and non-meditators.

Results from incon > con, non-meditators vs meditators

In a nutshell, the authors find that meditation-practitioners show faster reaction times with reduced BOLD-signal for the incongruent (compared to congruent and neutral) condition only. The regions found to be more active for non-meditators compared to meditators are the (right) “lentiform nucleus, medial frontal gyrus, and pre-central gyrus” . As this is not accompanied by any difference in accuracy, the authors interpret the finding as demonstrating  that “meditators may have maintained the focus in naming the colour with less interference of reading the word and consequently have to exert less effort to monitor the conflict and less adjustment in the motor control of the impulses to choose the correct colour button.” The authors in the conclusion review related findings and mention that differences in age could have contributed to the effect.

So, what are we to make of these findings? As is my usual style, I’ll give a bulleted review of the problems that immediately stand out, and then some explanation afterwards. I’ll preface my critique by thanking the authors for their hard work; my comments are intended only for the good of our research community.

The good:

  • Sensible findings; increases in reaction time and decreases in bold are demonstrated in areas previously implicated in meditation research
  • Solid, easy to understand behavioral paradigm
  • Relatively strong main findings ( P< .0001)
  • A simple replication. We like replications!
The bad:
  • Appears to report uncorrected p-values
  • Study claims to “match samples for age” yet no statistical test demonstrating no difference is shown. Qualitatively, the ages seem different enough to be cause for worry (77.8% vs 65% college graduates). Always be suspicious when a test is not given!
  • Extremely sparse description of style of practice, no estimate of daily practice hours given.
  • Reaction-time based task with no active control

I’ll preface my conclusion with something Sara Lazar, a meditation researcher and neuroimaging expert at the Harvard MGH told me last summer; we need to stop going for the “low hanging fruit of meditation research”. There are now over 20 published cross-sectional reaction-time based fMRI studies of “meditators” and “non-meditators”. Compare that to the incredibly sparse number of longitudinal, active controlled studies, and it is clear that we need to stop replicating these findings and start determining what they actually tell us. Why do we need to active control our meditation studies? For one thing, we know that reaction-time based tests are heavily based by the amount of effort one expends on the task. Effort is in turn influenced by task-demands (e.g. how you treat your participants, expectations surrounding the experiment). To give one in-press example, my colleagues Christian Gaden Jensen at the Copenhagen Neurobiology Research recently conducted a study demonstrating just how strong this confounding effect can be.

To briefly summarize, Christian recruited over 150 people for randomization to four experimental groups: mindfulness-based stress reduction (MBSR), non-mindfulness stress reduction (NMSR), wait-listed controls, and financially-motivated wait-listed controls. This last group is the truly interesting one; they were told that if they had top performance on the experimental tasks (a battery of classical reaction-time based and unspeeded perceptual threshold tasks) they’d receive a reward of approximately 100$. When Christian analyzed the data, he found that the financial incentive eliminated all reaction-time based differences between the MBSR, NMSR, and financially motivated groups! It’s important to note that this study, fully randomized and longitudinal, showed something not reflected in the bulk of published studies: that meditation may actually train more basic perceptual sensitivities rather than top-down control. This is exactly why we need to stop pursuing the low-hanging fruit of uncontrolled experimental design; it’s not telling us anything new! Meditation research is no longer exploratory.

In addition to these issues, there is another issue a bit more specific to meditation research. That is the totally sparse description of the practice- less than one sentence total, with no quantitative data! In this study we are not even told what the daily practice actually consists of, or its quality or length. These practitioners report an average of 8 years practice, yet that could be 1 hour per week of mantra meditation or 12 hours a week of non-dual zazen! These are not identical processes and our lack of knowledge for this sample severely limits our ability to assess the meaning of  these findings. For the past two years (and probably longer) of the Mind & Life Summer Research Institute, Richard Davidson and others have repeatedly stated that we must move beyond studying meditation as “a loose practice of FA and OM practices including x, y, z, & and other things”. Willoughby Britton suggested at a panel discussion that all meditation papers need to have at least one contemplative scholar on them or risk rejection. It’s clear that this study was most likely not reviewed by anyone with any serious academic background in meditation research.

My supervisor Antoine Lutz and his colleague John Dunne, authors of the paper that launched the “FA/OM” distinction, have since stated emphatically that we must go beyond these general labels and start investigating effects of specific meditation practices. To quote John, we need to stop treating meditation like a “black box” if we ever want to understand the actual mechanisms behind it. While I thank the authors of this paper for their earnest contribution, we need to take this moment to be seriously skeptical. We can only start to understand processes like meditation from a scientific point of view if we are willing to hold them to the highest of scientific standards. It’s time for us to start opening the black box and looking inside.

The 2011 Mind & Life Summer Research Institute: Are Monks Better at Introspection?

June 19th, 2011 § 4 Comments

As I’m sitting in the JFK airport waiting for my flight to Iceland, I can’t help but let my mind wander over the curious events of this year’s summer research institute (SRI). The Mind & Life Institute, an organization dedicated to the integration and development of what they’ve dubbed “contemplative science”, holds the SRI each summer to bring together clinicians, neuroscientists, scholars, and contemplatives (mostly monks) in a format that is half conference and half meditation retreat. The summer research institute is always a ton of fun, and a great place to further one’s understanding of Buddhism & meditation while sharing valuable research insights.

I was lucky enough to receive a Varela award for my work in meta-cognition and mental training and so this was my second year attending. I chose to take a slightly different approach from my first visit, when I basically followed the program and did whatever the M&L thought was the best use of my time. This meant lots of meditation- more than two hours per day not including the whole-day, silent “mini-retreat”. While I still practiced this year, I felt less obliged to do the full program, and I’m glad I took this route as it provided me a somewhat more detached, almost outsider view of the spectacle that is the Mind & Life SRI.

When I say spectacle, it’s important to understand how unconventional of a conference setting the SRI really is. Each year dozens of ambitious neuroscientists and clinicians meet with dozens of Buddhist monks and western “mindfulness” instructors. The initial feeling is one of severe culture clash; ambitious young scholars who can hardly wait to mention their Ivy League affiliations meet with the austere and almost ascetic approach of traditional Buddhist philosophy. In some cases it almost feels like a race to “out-mindful” one another, as folks put on a great show of piety in order to fit into the mood of the event. It can be a bit jarring to oscillate between the supposed tranquility and selflessness of mindfulness with the unabashed ambition of these highly talented and motivated folk- at least until things settle down a bit.

Nonetheless, the overall atmosphere of the SRI is one of serenity and scholarship. It’s an extremely fun, stimulating event, rich with amazingly talented yoga and meditation instructors and attended by the top researchers within the field. What follows is thus not meant as any kind of attack on the overall mission of the M&L. Indeed, I’m more than grateful to the institute for carrying on at least some form of Francisco Varela’s vision for cognitive science, and of course for supporting my own meditation research. With that being said, we turn to the question at hand: are monks objectively better at introspection? The answer for nearly everyone at the SRI appear to be “yes”, regardless of the scarcity of data suggesting this to be the case.

Enactivism and Francisco Varela

Francisco Varela, founder of EnactivismBefore I can really get into this issue, I need to briefly review what exactly “enactivism” is and how it relates to the SRI. The Mind & Life institute was co-founded by Francisco Varela, a Chilean biologist and neuroscientist who is often credited with the birth and success of embodied and enactive cognitive science. Varela had a profound impact on scientists, philosophers, and cognitive scientists and is a central influence in my own theoretical work. Varela’s essential thesis was outlined in his book “The Embodied Mind”, in which Varela, Thompson, and Rosch, attempted to outline a new paradigm for the study of mind. In the book, Varela et al rely on examples from cross-cultural psychology, continental phenomenology, Buddhism, and cognitive science to argue that cognition (and mind) is essentially an embodied, enactive phenomenon. The book has since spawned a generation of researchers dedicated in some way to the idea that cognition is not essentially, or at least foundationally, computational and representational in form.

I don’t here intend to get into the roots of what enactivism is; for the present it suffices to say that enactivism as envisioned by Varela involved a dedication to the “middle way” in which idealism-objectivism duality is collapsed in favor of a dynamical non-representational account of cognition and the world. I very much favor this view and try to use it productively in my own research. Varela argued throughout his life that cognition was not essentially an internal, info-processing kind of phenomenon, but rather an emergent and intricately interwoven entity that arose from our history of structural coupling with the world.  He further argued that cognitive science needed to develop a first-person methodology if it was to fully explain the rich panorama of human consciousness.

A simpler way to put this is to say that Varela argued persuasively that minds are not computers “parachuted into an objective world” and that cognition is not about sucking up impoverished information for representation in a subjective format. While Varela invoked much of Buddhist ontology, including concepts of “emptiness” and “inter-relatedness”, to develop his account continental phenomenologists like Heidegger and Merleau-Ponty also heavily inspired his vision of 4th wave cognitive science.  At the SRI there is little mention of this; most scholars are unaware of the continental literature or that phenomenology is not equal to introspection. Indeed I had to cringe when one to-be-unnamed young scientist declared a particular spinal pathway to be “the central pathway for embodiment”.

This is a stark misunderstanding of just what embodiment means, and I would argue renders it a relatively trivial add-on to the information processing paradigm- something most enactivists would like to strongly resist. I politely pointed the gentleman to the example work of Ulric Neisser, who argued for the ecological embodied self, in which the structure of the face is said to pre-structure human experience in particular ways, i.e. we typically experience ourselves as moving through the world toward a central fovea-centered point. Embodiment is an external, or pre-noetic structuring of the mind; it follows no nervous pathway but rather structures the possibilities of the nervous system and mind. I hope he follows that reference down the rabbit hole of the full possibilities of embodiment- the least of which is body-as-extra-module.

Still, I certainly couldn’t blame this particular scientist for his mis-understanding; nearly everyone at the SRI is totally unfamiliar with externalist/phenomenal perspectives, which is a sad state of affairs for a generation of scientists being supported by grants in Varela’s name. Regardless of Varela’s vision for cognitive science, his thesis regarding introspectionism is certainly running strong: first-person methodologies are the hot topic of the SRI, and nearly everyone agreed that by studying contemplative practitioners’ subjective reports, we’d gain some special insight into the mind.  Bracketing whether introspection is what Varela really meant by neurophenomenology (I don’t think it is- phenomenology is not introspection) we are brought to the central question: are Buddhist practitioners expert introspectionists?

Expertise and Introspectionism

Expert introspectionists?Varela certainly believed this to some degree. It’s not entirely clear to me that the bulk of Varela’s work summates to this maxim, but it’s at least certainly true that in papers such as his seminal “Neurophenomenology: a methodological remedy to the hard problem?” he argued that a careful first-person methodology could reap great benefits in this arena. Varela later followed up this theoretical thesis with his now well-known experiment conducted with then PhD student and my current mentor Antoine Lutz.

While I won’t reproduce the details of this experiment at length here, Lutz and Varela demonstrated that it was in fact possible to inform and constrain electrophysiological measurements through the collection and systemization of first-person reports. It’s worth noting here that the participants in this experiment were every day folks, not meditation practitioners, and that Lutz & Varela developed a special method to integrate the reports rather than taking them simply at face value. In fact, while Varela did often suggest that we might through careful contemplation and collaboration with the Buddhist tradition refine first person methodologies and gain insight into the “hard-problem”, he never did complete these experiments with practitioners, a fact that can likely be attributed to his pre-mature death at the hand of aggressive hepatitis.

Regardless of Varela’s own work, it’s fascinating to me that at today’s SRI, if there is one thing nearly everyone seems to explicitly agree on, it’s that meditation practitioners have some kind of privileged access to experience. I can’t count how many discussions seemed to simply assume the truth of this, regardless of the fact that almost no empirical research has demonstrated any kind of increased meta-cognitive capacity or accuracy in adept contemplatives.

While Antoine and I are in fact running experiments dedicated to answering this question, the fact remains that this research is largely exploratory and without strong empirical leads to work from. While I do believe that some level of meditation practice can provide greater reliability and accuracy in meta-cognitive reports, I don’t see any reason to value the reports of contemplative practitioners above and beyond those of any other particular niche group. If I want to know what it’s like to experience baseball, I’m probably going to ask some professional baseball players and not a Buddhist monk. At several points during the SRI I tried to express just this sentiment; that studying Buddhist monks gives us a greater insight into what-it-is-like to be a monk and not much else. I’m not sure if I succeeded, but I’d like to think I planted a few seeds of doubt.

There are several reasons for this. First, I part with Varela where he assumes that the Buddhist tradition and/or “Buddhist Psychology” have particularly valuable insights (for example, emptiness) that can’t be gleaned from western approaches. It might, but I don’t buy into the idea that the Buddhist tradition is its own kind of scientific approach to the mind; it’s not- it’s religion. For me the middle way means a lifelong commitment to a kind of meta-physical agnosticism, and I refuse to believe that any human tradition has a vast advantage over another. This was never more apparent than during a particularly controversial talk by John Dunne, a Harvard contemplative scholar, whose keynote was dedicated to getting scientists like myself to go beyond the traditional texts and veridical reports of practitioners and to instead engage in what he called “trialogue” in order to discover “what it is practitioners are really doing”. At the end of his talk one of the Dalai Lama’s lead monks actually took great offense, scolding John for “misleading the youth with his western academic approach”. The entire debacle was a perfect case-in-point demonstration of John’s talk; one cannot simply take the word of highly religious practitioners as some kind of veridical statement about the world.

This isn’t to say that we can’t learn a great deal about experience, and the mind, through meditation and careful introspection. I think at an early level it’s enough to just sit with ones breath and suspend beliefs about what exactly experience is. I do believe that in our modern lives; we spend precious little time with the body and our minds, simply observing what arises in a non-partial way.  I agree with Sogyal Rinpoche that we are at times overly dis-embodied and away from ourselves. Yet this practice isn’t unique to Buddhism; the phenomenological reduction comes from Husserl and is a practice developed throughout continental phenomenology. I do think that Buddhism has developed some particularly interesting techniques to aid this process, such as Vipassana and compassion-meditation, that can and will shed insights for the cognitive scientist interested in experience, and I hope that my own work will demonstrate as much.

But this is a very different claim from the one that says monastic Buddhists have a particularly special access to experience. At the end of the day I’m going to hedge my bets with the critical, empirical, and dialectical approach of cognitive science. In fact, I think there may be good reasons to suspect that high-level practitioners are inappropriate participants for “neurophenomenology”. Take for example, the excellent and controversial talk given this year by Willoughby Britton, in which she described how contemplative science had been too quick to sweep under the rug a vast array of negative “side-effects” of advanced practice. These effects included hallucination, de-personalization, pain, and extreme terror. This makes a good deal of sense; advanced meditation practice is less impartial phenomenology and more a rigorous ritualized mental practice embedded in a strong religious context. I believe that across cultures many religions share techniques, often utilizing rhythmic breathing, body postures, and intense belief priming to engender an almost psychedelic state in the practitioner.

What does this mean for cognitive science and enactivism? First, it means we need to respect cultural boundaries and not rush to put one cultural practice on top of the explanatory totem pole. This doesn’t mean cognitive scientists shouldn’t be paying attention to experience, or even practicing and studying meditation, but we have to be careful not to ignore the normativity inherent in any ritualized culture. Embracing this basic realization takes seriously individual and cultural differences in consciousness, something I’ve argued for and believe is essential for the future of 4th wave cognitive science. Neurophenomenology, among other things, should be about recognizing and describing the normativity in our own practices, not importing those of another culture wholesale. I think that this is in line with much of what Varela wrote, and luckily, the tools to do just this are richly provided by the continental phenomenological tradition.

I believe that by carefully bracketing meta-physical and normative concepts, and investigating the vast multitude of phenomenal experience in its full multi-cultural variety, we can begin to shed light on the mind-brain relationship in a meaningful and not strictly reductive fashion. Indeed, in answering the question “are monks expert introspectionists” I think we should carefully question the normative thesis underlying that hypothesis- what exactly constitutes “good” experiential reports? Perhaps by taking a long view on Buddhism and cognitive science, we can begin to truly take the middle way to experience, where we view all experiential reports as equally valid statements regarding some kind of subjective state. The question then becomes primarily longitudinal, i.e. do experiential reports demonstrate a kind of stability or consistency over time, how do trends in experiential reports relate to neural traits and states, and how do these phenomena interact with the particular cultural practices within which they are embedded. For me, this is the central contribution of enactive cognitive science and the best way forward for neurophenomenology.

Disclaimer: I am in no way suggesting enactivists cannot or should not study advanced buddhism if that is what they find interesting and useful. I of course realize that the M&L SRI is a very particular kind of meeting, and that many enactive cognitive scientists can and do work along the lines I am suggesting. My claim is regarding best practices for the core of 4th wave cognitive science, not the fringe. I greatly value the work done by the M&L and found the SRI to be an amazingly fruitful experience.

Uta Frith – The Curious Brain in the Museum

May 19th, 2011 § Leave a Comment

It’s not everyday that collaborations between the humanities and sciences lead to tangible fruits- but I’m excited to share with you one case in which they did, with surprisingly cute results! Leading development psychologist and Interacting Minds Research Foundation Professor, Uta Frith recently gave the Victoria and Albert Museum’s 2010 Henry Cole lecture. Below you will find the power-point slides from this talk, in which she discussed the relationship between her recent work on social learning and the experience of a museum. Interestingly, a film maker was inspired to put together the following short film, “The Curious Brain in the Museum.” It’s a very well done film and a fascinating look at the museum through Uta’s eyes.

Here are the slides from the talk:

And the resulting video:

In this short film, specially commissioned as part of the Royal Society’s 350th anniversary celebrations in 2010, Professor Uta Frith FRS and her young companion, Amalie Heath-Born, find out just what goes on inside our brains when we view the treasures on display at London’s world-famous Victoria and Albert Museum.

“The human mind/brain is exquisitely social and automatically responds to signals sent by other people. These signals can be artfully designed objects, and these can come from people long in the past. The art and design that is embodied in the object can evoke in the brain different streams of imagination: how it was made, the value it represents, and the meaning it conveys. The human mind/brain has ancient reward systems, which respond to, say, stimuli signaling food to the hungry, but also respond to social stimuli signaling relevance to the curious. This makes for a never ending well spring of spontaneous teaching and learning. Education in the museum environment is perfectly attuned to the curious mind.”  Uta Frith (2010)

You can read more about the event and the film on the Royal Society page.

Intrinsic correlations between Salience, Primary Sensory, and Default Mode Networks following MBSR

February 22nd, 2011 § 2 Comments

Going through my RSS backlog today, I was excited to see Kilpatrick et al.’s “Impact of Mindfulness-Based Stress Reduction Training on Intrinsic Brain Connectivity” appear in this week’s early view Neuroimage. Although I try to keep my own work focused on primary research in cognition and connectivity, mindfulness-training (MT) is a central part of my research. Additionally, there are few published findings on intrinsic connectivity in this area. Previous research has mainly focused on between-group differences in anatomical structure (gray and white matter for example) and task-related activity. A few more recent studies have gone as far as to randomize participants into wait-listed control and MT groups.

While these studies are interesting, they are of course limited in their scope by several factors. My supervisor Antoine Lutz emphasizes that in addition to our active-controlled research here in Århus, his group at Wisconsin-Madison and others are actively preparing such datasets. Active controls are simply ‘mock’ interventions (or real ones) designed to control for every possible aspect of being involved in an intervention (placebo, community, motivation) in order to isolate the variables specific to that treatment (in this case, meditation, but not sitting, breathing, or feeling special).  Active controls are important as there is a great deal of research demonstrating that cognition itself is susceptible to placebo-like motivational effects. All and all, I’ve seen several active-controlled, cognitive-behavioral studies in review that suggest we should be strongly skeptical of any non-active controlled findings. While I can’t discuss these in detail, I will mention some of these issues in my review of the neuroimage manuscript. It suffices to say however, that if you are working on a passive-controlled study in this area, you had better get it out fast as you can expect reviewers to be greatly tightening their expectations in the coming months, as more and more rigorous papers appear. As Sara Lazar put it during my visit to her lab last summer “the low-hanging fruit of MBSR brain research are rapidly vanishing”. Overall this is a good thing for the community and we’ll see why in a moment.

Now let us turn to the paper at hand. Kilpatrick et al start with a standard summary of MBSR and rsfMRI research, focusing on findings indicating MBSR trains focused attention, sensory introspection/interception and perception. They briefly review now well-established findings indicating that rsfMRI is sensitive to training related changes, including studies that demonstrate the sensitivity of the resting state to conditions such as fatigue, eyes-open vs eyes-closed, and recent sleep. This is all pretty well and good, but I think it’s a bit odd when we see just how they collect their data.

Briefly, they recruited 32 healthy adults for randomization to MBSR and waitlist controls. Controls then complete the Mindfulness Attention Awareness Scale (MAAS) and receive 8 weeks of diary-logged standard MBSR training. After training, participants are recalled for the rsfMRI scan. An important detail here is that participants are not scanned before and after training, rendering the fMRI portion of the experiment closer to a cross-section than true longitudinal design. At the time of scan, the researchers then give two ‘task-free states’, with and without auditory white noise. The authors indicate that the noise condition is included “to enable new analysis methods not conducted here”, presumably to average out scanner-noise related affects. They later indicate no differences between the two conditions, which causes me to ask how much here is meditation vs focusing-on-scanner-noise specific. Finally, they administer the ‘task free’ states with a slight twist:

“”During this baseline scan of about 5 min, we would like you to again stay as still as possible and be mindfully aware of your surroundings. Please keep your eyes closed during this procedure. Continue to be mindfully aware of whatever you notice in your surroundings and your own sensations. Mindful awareness means that you pay attention to your present moment experience, in this case the changing sounds of the scanner/changing background sounds played through the headphones, and to bring interest and curiosity to how you are responding to them.”

While the manipulation makes sense given the experimenter’s hypothesis concerning sensory processing, an ongoing controversy in resting-state research is just what it is that constitutes ‘rest’. Research here suggests that functional connectivity is sensitive to task-instructions and variations in visual stimulation, and many complain about the lack of specificity within different rest conditions. Kilpatrick et al’s manipulation makes sense given that what they really want to see is meditation-related alterations, but it’s a dangerous leap without first establishing the relationship between ‘true rest’ and their ‘auditory meditation’ condition. Research on the impact of scanner-noise indicates some degree of noise-related nuisance effects, and also some functionally significant effects. If you’ve never been in an MR experiment, the scanner is LOUD. During my first scan I actually started feeling claustrophobic due to the oppressive machine-gun like noise of the gradient coil. Anyway, it’s really troubling that Kilpatrick et al don’t include a totally task-free set for comparison, and I’m hesitant to call this a resting-state finding without further clarification.

The study is extremely interesting, but it’s important to note it’s limitations:

  1. Lack of active control- groups are not controlled for motivation.
  2. No pre/post scan.
  3. Novel resting state without comparison condition.
  4. Findings are discussed as ‘training related’ without report of correlation with reported practice hours.
  5. Anti-correlations reported with global-signal nuisance regression. No discussion of possible regression related inducement (see edit).
  6. Discussion of findings is unclear; reported as greater DMN x Auditory correlation, but the independent component includes large portions of the salience network.

Ultimately they identify a “auditory/salience” independent component network (ICN) (primary auditory, STG, posterior Insula, ACC, and lateral frontal cortex) and then conduct seed-regression analyses of the network with areas of the DMN and Dorsal Attention Network (DAN). I find it highly strange that they pick up a network that seems to conflate primary sensory and salience regions, as do the researchers who state “Therefore, the ICN was labeled as “auditory/salience”. It is unclear why the components split differently in our sample, perhaps the instructions that brought attention to auditory input altered the covariance structure somewhat.” Given the lack of motivational control in the study, the issues in this study begin to pile onto one another and I am not sure what we can really conclude. They further find that the MBSR group demonstrates greater “auditory/salience x DMN connectivity”, “greater visual and auditory functional connectivity” (see image below). They also report several increased anti-correlations, between the aud/sal network, dMPFC and visual regions. I find this to be an extremely tantalizing finding as it would reflect a decrease in processing automaticity amongst the SAL, CEN, and DMN networks. There are some serious problems with these kinds of analysis that the authors don’t address, and so we again must reserve any strong conclusions. Here is what Kilpatrick et al conclude:

“The current findings extend the results of prior studies that showed meditation-related changes in specific brain regions active during attention and sensory processing by providing evidence that MBSR trained compared to untrained subjects, during a focused attention instruction, have increased connectivity within sensory networks and between regions associated with attentional processes and those in the attended sensory cortex. In addition they show greater differentiation between regions associated with attentional processes and the unattended sensory cortex as well as greater differentiation between attended and unattended sensory networks”

As is typical, the list of findings is quite long and I won’t bother re-stating it all here. Given the resting instructions it seems clear that the freshly post-MBSR participants are likely to have engaged a pretty dedicated set of cognitive operations during the scan. Yet it’s totally unclear what the control group would do given these contemplative instructions. Presumably they’d just lie in the scanner and try not to tune out the noise- but you can see here how it’s not clear that these conditions are really that comparable without having some idea of what’s going on. In essence what you (might) have here is one group actually doing something (meditation) and the other group not doing much at all. Ideally you want to see how training impacts the underlying process in a comparable way. Motivation has been repeatedly linked to BOLD signal intensity and in this case, it could very well be that these findings are simple artifacts of motivation to perform. If one group is actually practicing mindfulness and the other isn’t, you have not isolated the variable of interest. The authors could have somewhat alleviated this by including data from the additional pain task (“not reported here”) and/or at least giving us a correlation of the findings with the MAAS scale. I emphasize that I do find the findings of this paper interesting- they map extremely well onto my own hypotheses about how RSNs interact with mindfulness training, but that we must interpret them with caution.

Overall I think this was a project with a strong theoretical motivation and some very interesting ideas. One problem with looking at state-mindfulness in the scanner is the cramped, noisy environment. I think Kilpatrick et al had a great idea in their attempt to use the noise itself as a manipulation. Further, the findings make a good deal of sense. Still, given the above limitation, it’s important to be really careful with our conclusions. At best, this study warrants an extremely rigorous follow-up, and I wish neuroimage had published it with a bit more information, such as the status of any rest-MAAS correlations. Anyway, this post has gotten quite long and I think I’d best get back to work- for my next post I think I’ll go into more detail about some of the issues confront resting state (what is “rest”?) and mindfulness (role of active controls for community, motivation, and placebo effects) and what they mean for resting-state research.

edit: just realized I never explained limitation #5. See my “beautiful noise” slides (previous post) regarding the controversy of global signal regression and anti-correlation. Simply put, there is somewhat convincing evidence that this procedure (designed to eliminate low-frequency nuisance co-variates) may actually mathematically induce anti-correlations where none exist, probably due to regression to the mean. While it’s not a slam-dunk (see response by Fox et al), it’s an extremely controversial area and all anti-correlative findings should be interpreted in light of this possibility.

If you like this post please let me know in the comments! If I can get away with rambling about this kind of stuff, I’ll do so more frequently.

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