Does Mindfulness lead to neuroplasticity? Summary of my recent paper.

by Neuroconscience

First, let me apologize for an overlong hiatus from blogging. I submitted my PhD thesis October 1st, and it turns out that writing two papers and a thesis in the space of about three months can seriously burn out the old muse. I’ve coaxed her back through gentle offerings of chocolate, caffeine, and a bit of videogame binging. As long as I promise not to bring her within a mile of a dissertation, I believe we’re good for at least a few posts per month.

With that taken care of, I am very happy to report the successful publication of my first fMRI paper, published last month in the Journal of Neuroscience. The paper was truly a labor of love taking nearly 3 years to complete and countless hours of head-scratching work. In the end I am quite happy with the finished product, and I do believe my colleagues and I managed to produce a useful result for the field of mindfulness training and neuroplasticity.

note: this post ended up being quite long. if you are already familiar with mindfulness research, you may want to skip ahead!

Why mindfulness?

First, depending on what brought you here, you may already be wondering why mindfulness is an interesting subject, particularly for a cognitive neuroscientist. In light of the large gaps regarding our understanding of the neurobiological foundations of neuroimaging, is it really the right time to apply these complex tools to meditation?  Can we really learn anything about something as potentially ambiguous as “mindfulness”? Although we have a long way to go, and these are certainly fair questions, I do believe that the study of meditation has a lot to contribute to our understanding of cognition and plasticity.

Generally speaking, when you want to investigate some cognitive phenomena, a firm understanding of your target is essential to successful neuroimaging. Areas with years of behavioral research and concrete theoretical models make for excellent imaging subjects, as in these cases a researcher can hope to fall back on a sort of ‘ground truth’ to guide them through the neural data, which are notoriously ambiguous and difficult to interpret. Of course well-travelled roads also have their disadvantages, sometimes providing a misleading sense of security, or at least being a bit dry. While mindfulness research still has a ways to go, our understanding of these practices is rapidly evolving.

At this point it helps to stop and ask, what is meditation (and by extension, mindfulness)? The first thing to clarify is that there is no such thing as “meditation”- rather meditation is really term describing a family resemblance of highly varied practices, covering an array of both spiritual and secular practices. Meditation or “contemplative” practices have existed for more than a thousand years and are found in nearly every spiritual tradition. More recently, here in the west our unending fascination of the esoteric has lead to a popular rise in Yoga, Tai Chi, and other physically oriented contemplative practices, all of which incorporate an element of meditation.

At the simplest level of description [mindfulness] meditation is just a process of becoming aware, whether through actual sitting meditation, exercise, or daily rituals.  Meditation (as a practice) was first popularized in the west during the rise of transcendental meditation (TM). As you can see in the figure below, interest in TM lead to an early boom in research articles. This boom was not to last, as it was gradually realized that much of this initially promising research was actually the product of zealous insiders, conducted with poor controls and in some cases outright data fabrication. As TM became known as  a cult, meditation research underwent a dark age where publishing on the topic could seriously damage a research career. We can see also that around the 1990′s, this trend started to reverse as a new generation of researchers began investigating “mindfulness” meditation.

pubmed graphy thing

Sidenote: research everywhere is expanding. Shouldn’t we start controlling these highly popular “pubs over time” figures for total publishing volume? =)

It’s easy to see from the above why when Jon Kabat-Zinn re-introduced meditation to the West, he relied heavily on the medical community to develop a totally secularized intervention-oriented version of meditation strategically called “mindfulness-based stress reduction.” The arrival of MBSR was closely related to the development of mindfulness-based cognitive therapy (MBCT), a revision of cognitive-behavioral therapy utilizing mindful practices and instruction for a variety of clinical applications. Mindfulness practice is typically described as involving at least two practices; focused attention (FA) and open monitoring (OM). FA can be described as simply noticing when attention wanders from a target (the breath, the body, or a flower for example) and gently redirecting it back to that target. OM is typically (but not always) trained at an later stage, building on the attentional skills developed in FA practice to gradually develop a sense of “non-judgmental open awareness”. While a great deal of work remains to be done, initial cognitive-behavioral and clinical research on mindfulness training (MT) has shown that these practices can improve the allocation of attentional resources, reduce physiological stress, and improve emotional well-being. In the clinic MT appears to effectively improve symptoms on a variety of pathological syndromes including anxiety and depression, at least as well as standard CBT or pharmacological treatments.

Has the quality of research on meditation improved since the dark days of TM? When answering this question it is important to note two things about the state of current mindfulness research. First, while it is true that many who research MT are also practitioners, the primary scholars are researchers who started in classical areas (emotion, clinical psychiatry, cognitive neuroscience) and gradually became involved in MT research. Further, most funding today for MT research comes not from shady religious institutions, but from well-established funding bodies such as the National Institute of Health and European Research Council. It is of course important to be aware of the impact prior beliefs can have on conducting impartial research, but with respect to today’s meditation and mindfulness researchers, I believe that most if not all of the work being done is honest, quality research.

However, it is true that much of the early MT research is flawed on several levels. Indeed several meta-analyses have concluded that generally speaking, studies of MT have often utilized poor design – in one major review only 8/22 studies met criteria for meta-analysis. The reason for this is quite simple- in the absence of pilot data, investigators had to begin somewhere. Typically it doesn’t bode well to jump into unexplored territory with an expensive, large sample, fully randomized design. There just isn’t enough to go off of- how would you know which kind of process to even measure? Accordingly, the large majority of mindfulness research to date has utilized small-scale, often sub-optimal experimental design, sacrificing experimental control in order build a basic idea of the cognitive landscape. While this exploratory research provides a needed foundation for generating likely hypotheses, it is also difficult to make any strong conclusions so long as methodological issues remain.

Indeed, most of what we know about these mindfulness and neuroplasticity comes from studies of either advanced practitioners (compared to controls) or “wait-list” control studies where controls receive no intervention. On the basis of the findings from these studies, we had some idea how to target our investigation, but there remained a nagging feeling of uncertainty. Just how much of the literature would actually replicate? Does mindfulness alter attention through mere expectation and motivation biases (i.e. placebo-like confounds), or can MT actually drive functionally relevant attentional and emotional neuroplasticity, even when controlling for these confounds?

The name of the game is active-control

Research to date links mindfulness practices to alterations in health and physiology, cognitive control, emotional regulation, responsiveness to pain, and a large array of positive clinical outcomes. However, the explicit nature of mindfulness training makes for some particularly difficult methodological issues. Group cross-sectional studies, where advanced practitioners are compared to age-matched controls, cannot provide causal evidence. Indeed, it is always possible that having a big fancy brain makes you more likely to spend many years meditating, and not that meditating gives you a big fancy brain. So training studies are essential to verifying the claim that mindfulness actually leads to interesting kinds of plasticity. However, unlike with a new drug study or computerized intervention, you cannot simply provide a sugar pill to the control group. Double-blind design is impossible; by definition subjects will know they are receiving mindfulness. To actually assess the impact of MT on neural activity and behavior, we need to compare to groups doing relatively equivalent things in similar experimental contexts. We need an active control.

There is already a well-established link between measurement outcome and experimental demands. What is perhaps less appreciated is that cognitive measures, particularly reaction time, are easily biased by phenomena like the Hawthorne effect, where the amount of attention participants receive directly contributes to experimental outcome. Wait-lists simply cannot overcome these difficulties. We know for example, that simply paying controls a moderate performance-based financial reward can erase attentional reaction-time differences. If you are repeatedly told you’re training attention, then come experiment time you are likely expect this to be true and try harder than someone who has received no such instruction. The same is true of emotional tasks; subjects told frequently they are training compassion are likely to spend more time fixating on emotional stimuli, leading to inflated self-reports and responses.

I’m sure you can quickly see how it is extremely important to control for these factors if we are to isolate and understand the mechanisms important for mindfulness training. One key solution is active-control, that is providing both groups (MT and control) with a “treatment” that is at least nominally as efficacious as the thing you are interested in. Active-control allows you exclude numerous factors from your outcome, potentially including the role of social support, expectation, and experimental demands. This is exactly what we set out to do in our study, where we recruited 60 meditation-naïve subjects, scanned them on an fMRI task, randomized them to either six weeks of MT or active-control, and then measured everything again. Further, to exclude confounds relating to social interaction, we came up with a particularly unique control activity- reading Emma together.

Jane Austen as Active Control – theory of mind vs interoception

To overcome these confounds, we constructed a specialized control intervention. As it was crucial that both groups believed in their training, we needed an instructor who could match the high level of enthusiasm and experience found in our meditation instructors. We were lucky to have the help of local scholar Mette Stineberg, who suggested a customized “shared reading” group to fit our purposes. Reading groups are a fun, attention demanding exercise, with purported benefits for stress and well-being. While these claims have not been explicitly tested, what mattered most was that Mette clearly believed in their efficacy- making for a perfect control instructor. Mette holds a PhD in literature, and we knew that her 10 years of experience participating in and leading these groups would help us to exclude instructor variables from our results.

With her help, we constructed a special condition where participants completed group readings of Jane Austin’s Emma. A sensible question to ask at this point is – “why Emma?” An essential element of active control is variable isolation, or balancing your groups in such way that, with the exception of your hypothesized “active ingredient”, the two interventions are extremely similar. As MT is thought to depend on a particular kind of non-judgmental, interoceptive kind of attention, Chris and Uta Frith suggested during an early meeting that Emma might be a perfect contrast. For those of you who haven’t read the novel, the plot is brimming over with judgment-heavy theory-of-mind-type exposition. Mette further helped to ensure a contrast with MT by emphasizing discussion sessions focused on character motives. In this way we were able to ensure that both groups met for the same amount of time each week, with equivalently talented and passionate instructors, and felt that they were working towards something worthwhile. Finally, we made sure to let every participant know at recruitment that they would receive one of two treatments intended to improve attention and well-being, and that any benefits would depend upon their commitment to the practice. To help them practice at home, we created 20-minute long CD’s for both groups, one with a guided meditation and the other with a chapter from Emma.

Unlike previous active-controlled studies that typically rely on relaxation training, reading groups depend upon a high level of social-interaction. Reading together allowed us not only to exclude treatment context and expectation from our results, but also more difficult effects of social support (the “making new friends” variable). To measure this, we built a small website for participants to make daily reports of their motivation and minutes practiced that day. As you can see in the figure below, when we averaged these reports we found that not only did the reading group practice significantly more than those in MT, but that they expressed equivalent levels of motivation to practice. Anecdotally we found that reading-group members expressed a high level of satisfaction with their class, with a sub-group of about 8 even continued their meetings after our study concluded. The meditation group by comparison, did not appear to form any lasting social relationships and did not continue meeting after the study. We were very happy with these results, which suggest that it is very unlikely our results could be explained by unbalanced motivation or expectation.

Impact of MT on attention and emotion

After we established that active control was successful, the first thing to look at was some of our outside-the-scanner behavioral results. As we were interested in the effect of meditation on both attention and meta-cognition, we used an “error-awareness task” (EAT) to examine improvement in these areas. The EAT (shown below) is a typical “go-no/go” task where subjects spend most of their time pressing a button. The difficult part comes whenever a “stop-trial” occurs and subject must quickly halt their response. In the case where the subject fails to stop, they then have the opportunity to “fix” the error by pressing a second button on the trial following the error. If you’ve ever taken this kind of task, you know that it can be frustratingly difficult to stop your finger in time – the response becomes quite habitual. Using the EAT we examined the impact of MT on both controlling responses (a variable called “stop accuracy”), as well as also on meta-cognitive self-monitoring (percent “error-awareness”).

The error-awareness task

We started by looking for significant group by time interactions on stop accuracy and error-awareness, which indicate that score fluctuation on a measure was statistically greater in the treatment (MT) group than in the control group. In repeated-measures design, this type of interaction is your first indication that the treatment may have had a greater effect than the control group. When we looked at the data, it was immediately clear that while both groups improved over time (a ‘main effect’ of time), there was no interaction to be found:

Group x time analysis of SA and EA.

While it is likely that much of the increase over time can be explained by test-retest effects (i.e. simply taking the test twice), we wanted to see if any of this variance might be explained by something specific to meditation. To do this we entered stop accuracy and error-awareness into a linear model comparing the difference of slope between each group’s practice and the EAT measures. Here we saw that practice predicted stop accuracy improvement only in the meditation group, and that the this relationship was statistically greater than in the reading group:

Practice vs Stop accuracy (MT only shown). We did of course test our interaction, see paper for GLM goodness =)

These results lead us to conclude that while we did not observe a treatment effect of MT on the error-awareness task, the presence of strong time effects and MT-only correlation with practice suggested that the improvements within each group may relate to the “active ingredients” of MT but reflect motivation-driven artifacts in the reading group. Sadly we cannot conclude this firmly- we’d have needed to include a third passive control group for comparison. Thankfully this was pointed out to us by a kind reviewer, who noted that this argument is kind of like having one’s cake and eating it, so we’ll restrict ourselves to arguing that the EAT finding serves as a nice validation of the active control- both groups improved on something, and a potential indicator of a stop-related treatment mechanism.

While the EAT served as a behavioral measure of basic cognitive processes, we also wanted to examine the neural correlates of attention and emotion, to see how they might respond to mindfulness training in our intervention. For this we partnered with Karina Blair at the National Institute of Mental Health to bring the Affective Stroop task (shown below) to Denmark .

Affective Stroop Trial Scheme

The Affective Stroop Task (AST) depends on a basic “number-counting Stroop” to investigate the neural correlates of attention, emotion, and their interaction. To complete the task, your instruction is simply “count the number of numbers in the first display (of numbers), count the number of numbers in the second display, and decide which display had more number of numbers”.  As you can see in the trial example above, conflict in the task (trial-type “C”) is driven by incongruence between the Arabic numeral (e.g. “4”) and the numeracy of the display (a display of 5 “4”’s). Meanwhile, each trial has nasty or neutral emotional stimuli selected from the international affective picture system. Using the AST, we were able to examine the neural correlates of executive attention by contrasting task (B + C > A) and emotion (negative > neutral) trials.

Since we were especially interested in changes over time, we expanded on these contrasts to examine increased or decreased neural response between the first and last scans of the study. To do this we relied on two levels of analysis (standard in imaging), where at the “first” or “subject level” we examined differences between the two time points for each condition (task and emotion), within each subject. We then compared these time-related effects (contrast images) between each group using a two-sample t-test with total minutes of practice as a co-variate. To assess the impact of meditation on performing the AST, we examined reaction times in a model with factors group, time, task, and emotion. In this way we were able to examine the impact of MT on neural activity and behavior while controlling for the kinds of artifacts discussed in the previous section.

Our analysis revealed three primary findings. First, the reaction time analysis revealed a significant effect of MT on Stroop conflict, or the difference between reaction time to incongruent versus congruent trials. Further, we did not observe any effect on emotion-related RTs- although both groups sped up significantly to negative trials vs neutral (time effect), this increase was equivalent in both groups. Below you can see the stroop-conflict related RTs:

Stroop conflict result

This became particularly interesting when we examine the neural response to these conditions, and again observed a pattern of overall [BOLD signal] increases in the dorsolateral prefrontal cortex to task performance (below):

DLPFC increase to task

Interestingly, we did not observe significant overall increases to emotional stimuli  just being in the MT group didn’t seem to be enough to change emotional processing. However, when we examined correlations with amount practice and increased BOLD to negative emotion across the whole brain, we found a striking pattern of fronto-insular BOLD increases to negative images, similar to patterns seen in previous studies of compassion and mindfulness practice:

Greater association of prefrontal-insular response to negative emotion and practice

Greater association of prefrontal-insular response to negative emotion and practice.

When we put all this together, a pattern began to emerge. Overall it seemed like MT had a relatively clear impact on attention and cognitive control. Practice-correlated increases on EAT stop accuracy, reduced Affective Stroop conflict, and increases in dorsolateral prefrontal cortex responses to task all point towards plasticity at the level of executive function. In contrast our emotion-related findings suggest that alterations in affective processing occurred only in MT participants with the most practice. Given how little we know about the training trajectories of cognitive vs affective skills, we felt that this was a very interesting result.

Conclusion: the more you do, the what you get?

For us, the first conclusion from all this was that when you control for motivation and a host of other confounds, brief MT appears to primarily train attention-related processes. Secondly, alterations in affective processing seemed to require more practice to emerge. This is interesting both for understanding the neuroscience of training and for the effective application of MT in clinical settings. While a great deal of future research is needed, it is possible that the affective system may be generally more resilient to intervention than attention. It may be the case that altering affective processes depends upon and extends increasing control over executive function. Previous research suggests that attention is largely flexible, amenable to a variety of training regimens of which MT is only one beneficial intervention. However we are also becoming increasingly aware that training attention alone does not seem to directly translate into closely related benefits.

As we begin to realize that many societal and health problems cannot be solved through medication or attention-training alone, it becomes clear that techniques to increase emotional function and well-being are crucial for future development.  I am reminded of a quote overheard at the Mind & Life Summer Research Institute and attributed to the Dalai Lama. Supposedly when asked about their goal of developing meditation programs in the west, HHDL replied that, what was truly needed in the West was not “cognitive training, as (those in the west) are already too clever. What is needed rather is emotion training, to cultivate a sense of responsibility and compassion”. When we consider falling rates of empathy in medical practitioners and the link to health outcome, I think we do need to explore the role of emotional and embodied skills in supporting a wide-array of functions in cognition and well-being. While emotional development is likely to depend upon executive function, given all the recent failures to show a transfer from training these domains to even closely related ones, I suspect we need to begin including affective processes in our understanding of optimal learning. If these differences hold, then it may be important to reassess our interventions (mindful and otherwise), developing training programs that are customized in terms of the intensity, duration, and content appropriate for any given context.

Of course, rather than end on such an inspiring note, I should point out that like any study, ours is not without flaws (you’ll have to read the paper to find out how many ;) ) and is really just an initial step. We made significant progress in replicating common neural and behavioral effects of MT while controlling for important confounds, but in retrospect the study could have been strengthened by including measures that would better distinguish the precise mechanisms, for example a measure of body awareness or empathy. Another element that struck me was how much I wish we’d had a passive control group, which could have helped flesh out how much of our time effect was instrument reliability versus motivation. As far as I am concerned, the study was a success and I am happy to have done my part to push mindfulness research towards methodological clarity and rigor. In the future I know others will continue this trend and investigate exactly what sorts of practice are needed to alter brain and behavior, and just how these benefits are accomplished.

In the near-future, I plan to give mindfulness research a rest. Not that I don’t find it fascinating or worthwhile, but rather because during the course of my PhD I’ve become a bit obsessed with interoception and meta-cognition. At present, it looks like I’ll be spending my first post-doc applying predictive coding and dynamic causal modeling to these processes. With a little luck, I might be able to build a theoretical model that could one day provide novel targets for future intervention!

Link to paper:

Cognitive-Affective Neural Plasticity following Active-Controlled Mindfulness Intervention

Thanks to all the collaborators and colleagues who made this study possible.

Special thanks to Kate Mills (@le_feufollet) for proofing this post :)