Year in review: 2016

#2016.

Somewhat of an annus horribilis, opening with the abhorrent mass attack on women in Cologne, and where the deaths of (increasingly) numerous celebrities was broadly overshadowed by the political upsets of Brexit and the election of Donald Trump. The questions that have interested me in the last few years may seem to be more "micro" compared to these bigger trends, and yet they still remain...

In ketamine and depression research, it was interesting to see some preclinical work published in super journal Nature examining if ketamine metabolites may have similar antidepressant effects with a less severe side effect profile, seemingly through their impact on a more specific set of receptors. Although I would question the scope for modelling ketamine side effects as psychologically complex as dissociation in animals, it will be interesting to see human trials in future.

With research that I had been involved with getting exposure, it was also of interest to see a trial on probiotics in depression indicate promising results. Researchers from Iran ran a double-blind, placebo-controlled trial in patients with depression, and found that patients who took a mix of probiotic bacteria had reduced depression scores compared to those who took a placebo.

The dialogue concerning people's first-hand experiences of mental health continued, from a viral video of a young Irish man discussing his experience of depression (despite a happy-go-lucky outward appearance), to a former Trinity classmate of mine "outing himself" as having bipolar disorder, to an interesting account of a psychologist who described how his experience of manic periods were overall a positive thing for him (albeit he did encounter problems with them).

In the arts world, Dublin writer Rob Doyle's book of short fiction This is the Ritual contained a number of pieces with a strong psychological focus. The story of a young man trying to write a book about Nietzsche, but unable to begin due to his perceived lack of knowledge of the contemporary intellectual context of the philosopher, touches on themes of motivation, sustained attention and imposter syndrome. Other pieces stray into fairly Burroughs-like "Naked Lunch" territory, but the collection as a whole is a good intro to his style. However, if you haven't checked out Doyle's debut novel"Here are the Young Men" yet, please do!

A debut novel from an author from further afield, Emma Cline's The Girls, dealt with a somewhat masochistic protagonist who takes up with a group of charismatic characters. It is essentially a roman a clef about Charles Manson from the point of view of a woman who was involved with his group. However, the focus is generally drawn away from the crimes to broader trends in the character's psyche.

Next year should be an interesting one-watch this space for microbiota and stress stuff coming from my current research program. Some reviews are also hitting the presses that I'll be commenting on next month.

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2015: year in review

Probiotics and cognition

Calvin: "I wish I could just take a pill to be perfect and I wish I could just push a button to have anything I want"
Hobbes: "The American Dream lives on"
Calvin & Hobbes, Bill Watterson


The dream Hobbes refers to is, of course, shared by many outside of the United States. There is an obvious demand for dietary supplements that can improve health in some way. Given the general lack of adverse side effects, probiotics represent an attractive opportunity for improving health.

Previous research has indicated that consuming a fermented milk product with probiotic can alter a network of brain regions associated with emotional-as well as visceral-processing. Sadly, the article did not report how people performed on the task the researchers used. As this task just involved classifying emotions on faces, I suspect that maybe performance was too close to ceiling to demonstrate an effect of the probiotic.

As noted in a recent post, we found that participants reported less stress over weeks of consuming probiotic compared to a strain of Bifidobacerium longum. Interestingly, we also found that participants performed best at a test of visuospatial memory after having consumed the probiotic strain. This particular memory test we looked at (paired associates learning) is dependent upon the hippocampus, a region of the brain that can be affected by cortisol secretion following stress. It may thus be the case that a lower level of stress may account for the improved performance on the memory test.

We also assessed electroencephalography (a method of measuring brain activity via electrodes placed on the scalp), and observed that there was enhanced activity at frontal regions following probiotic consumption, consistent with improved memory. This is not just another way of showing what had already been demonstrated with the participant's memory performance, as frontal processing is associated with top-down processing (i.e. processing relating to motivation and broader context, as opposed to bottom-up/driven by the sensation or perception).

However, the picture is complicated by a more recent study from our group seeking to show similar effects with a different probiotic strain; the results here did not indicate effects on cognition (or stress), despite the fact that we used the same assessments, and despite very promising initial results in animal models with this second bacteria. It thus seems to be the case that specific effects go with specific bacteria. Perhaps we are just at the beginning of understanding how gastrointestinal health can be harnessed to improve brain health.

John R. Kelly, Andrew P. Allen, Andriy Temko, William Hutch, Paul J. Kennedy, Niloufar Farid, Eileen Murphy, Geraldine Boylan, John Bienenstock, John F. Cryan, Gerard Clarke, Timothy G. Dinan, (in press). Lost in Translation? The potential psychobiotic Lactobacillus rhamnosus (JB-1) fails to modulate stress or cognitive performance in healthy male subjects, Brain, Behavior, and Immunity. doi: 10.1016/j.bbi.2016.11.018.

Related posts:
Probiotics and stress
Myelin and the gut
Irritable bowel syndrome

Probiotics and stress

With the increased research interest in the interactions between the brain and the gut, people are curious whether we can affect the brain in desirable ways by targeting the gut. Existing evidence from France has indicated that taking a probiotic can reduce psychological distress and urinary levels of cortisol (a hormone associated with stress).

Previous research from our own group in animal models indicated that a strain of bacteria-Bif. Longum 1714-could reduce the physiological stress response. The 1714 strain was associated with reduced stress-induced hyperthermia, as well as reduced depression-like behaviour. Given these findings, there was interest in whether the bacteria could have similar stress-reducing effects in humans.

Participants took the probiotic for 4 weeks and the placebo for 4 weeks. (Both came in the form of a white powder that one mixes into milk each morning). Participants filled in daily online questionnaires assessing their perceived stress levels-during probiotic supplementation stress levels started off at a similar level, but were reduced by the final week of taking the probiotic.

So far, the results were similar to what the group in France found. But we took things a step further by seeing how people would respond to a controlled stressor after taking the probiotic. At baseline and following each of the 4 week periods they were exposed to a socially evaluated cold pressor test. One has to immerse one's hand in ice cold water for up to 3 minutes. After taking the probiotic, participants showed lessened cortisol output in response to the stressor. Furthermore, although anxiety levels were heightened by the stressor at all visits, the increase was lessened following the probiotic.

Interesting stuff, but further research will be needed to determine how the bacteria is having these effects-we know that bacteria can produce neurochemicals that affect factors such as mood, but we're still in the early days of trying to work out the process through which this leads to knock-on effects on the brain.

We have presented the findings at conferences such as Neuroscience Ireland and Society for Neuroscience (you can download the relevant posters from the Department of Psychiatry website) and the results  have received coverage in numerous mainstream outlets, including The Guardian and The Huffington Post. As usual, things move a bit more slowly in academia, but we have the research paper out now too-it's open access, so anyone with an internet connection can access it:

Allen, A. P., Hutch, W., Borre, Y. E., Kennedy, P. J., Temko, A., Boylan, G., Murphy, E., Cryan, J.F. Dinan, T.G., & Clarke, G. (2016). Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers. Translational Psychiatry, 6(11), e939.

Related posts:
Irritable bowel syndrome
Myelin and bacteria
From the depths came the form

Why a randomer could NOT have told you that

(The title is a play on Susie Hodge's book on visual art, "Why your five year old could not have done that")

As someone who studies psychology, few things grind my gears like someone pointing out that the latest psychological findings are something that their grandmother could have told them. Regardless of how much psychological insight their own grandmothers may have, there are always some people willing to tell you that you are wasting public or private funds on investigating a question to which people have known the answer for generations.

If someone says they are a quantum physicist or a brain surgeon, most people who do not share the profession would be hesitant to try and opine on quantum physics or brain surgery. Regardless of what you do in life, however, it is likely that your mind is geared to some extent towards developing theories about the thoughts of others around you. You see two managers in work who employ very different management styles, and you come up with hypotheses as to why each manager chose that style, as well as which style works best with which employee. You are spending a few weeks studying for exams, so you test which learning strategies work best to help you memorise as much information as you can.

..and people have been doing this since before there was a discipline called psychology. So of course, when you see a news report on a new finding from a psychological study, it chimes with something you heard from someone else, who was really just speaking from good old-fashioned experience and a bit of introspection. When you remember what that person said, it may feel that what you’re hearing is not really news at all.

So why bother doing psychological research? Here’s a couple of quick reasons why…

At a basic level, empirical psychology can be used to quantify the extent of phenomena we may already be aware of. The fact that people were willing to comply with Milgram’s commands to administer high electric shocks to strangers may chime with people’s intuitions, but the rate of compliance was considerably higher than predicted. We all know that staying awake all night is generally not good for reaching optimal performance, but is it enough to make junior doctors perform worse at the level of basic attention? This is an empirical question.

But we can go further in saying that psychological research can often demonstrate the direction of an effect (i.e. whether x increases or decreases y), where everyday theorising would fail. Why? It’s worth bearing in mind that intuition can come up with two opposing predictions that both make sense at an a priori level.  What effect does stress have on cognition? Well, it’s distracting, so it should have a negative effect on how you think. No wait, it’s motivating, so it should have a positive effect. But when people see a report that confirms one, they may only think of the intuition that chimed with the observed effect, thereby making seem that the researchers were just stating the obvious.

Even when armchair psychology is prone to predicting an effect in a particular direction, the research may contradict this. A while back BPS digest published an interesting post concerning counter-intuitive findings in psychology. Check it out!

Related links
On established validity and good questions

The autocerebroscope

The Autocerebroscope

I

*Wind chimes sound as Andrew opens the office door”

Why hello Andrew, what brings you here?

Hello Professor, I’ve been studying the brain and the mind for some time now, but I want to find some way of gaining greater insight into how the function of the mind-you know, thinking, emotion and so on-is produced by the physical brain. I just want an intuitive, first-hand sense of how it all 
happens!

Well Andrew, I have just the thing for you! This is the autocerebroscope; a device will allow you to see inside your own brain as it works. Let’s say you’re eating a delicious falafel-flavoured chocolate. The autocerebroscope will show you the oxygenated blood flowing to your occipital lobe as you process the visual stimulus, your motor cortices working to chew the food, your nucleus accumbens going into overdrive as you feel the intense pleasure of the tasty choco…the works!

Sounds amazing-so I’ll be able to see changes in my own brain activity as they happen-I’ll take it home and try it out!

*Andrew exits*

II

*Wind chimes jangle*

Well well Andrew, what can I do you for?

Hello Professor, I’m blown away by this thing! The autocerebroscope does exactly what you said that it would.

Pretty impressive, yes?

Absolutely! It’s just…

Yes?

The problem is that I want to know more than which brain regions are being activated. I want to gain some insight into how they are working together to produce the workings of the mind. At the moment I can say that when I’m involved in problem solving I’m using my prefrontal cortex, but I’m not sure how the various sub-regions of this cortex are working together to solve the problem.

Okay, well how about I give you insight not only into which regions of the brain are being activated as you think, but also which neural impulses are going from one part of the brain to the other?

That sounds great, but I can foresee a roadblack; I can only process so much information in real time within my own brain as this same brain generates its vastly complex activity.

No problemo, We will give you an add-in that produces a summary of the inputs that are being sent from one brain region to the other. You may have to use memory a bit, as there may be a bit of a lag, but it should give you an even deeper insight into the workings of your own brain! I’ll see you later-take your time practicing with that bad boy.

III

*Ding a ling a ling*

Hello Professor, good to see you again.

You must have some tremendous insights by now Andrew!

To be honest, I feel that I’ve made less progress this time. When I read the outputs, well, they do seem to be a summary of very many neural impulses.

Yeah, pretty cool, right?

Absolutely! It’s just that there doesn’t seem to be fully meaningful correspondence between the concepts as I experience them and the information going from one brain region to the other. When I was smelling a half-empty crisp packet that I found in the rubbish the other day I could see a whole hosts of impulses in my brain corresponding to constituent compounds making up the smell. In theory these impulses based on compounds should add up to the overall sense of the odour, but when I looked at the outputs coming and going between the various parts of the brain I couldn’t see the Gestalt of the scent as a whole.

Hmm, it seems like these concepts are being produced by the interaction of various activities between various different brain regions.

But I want a real-time readout that will allow me to gain sufficient insight into the workings of my own brain that correspond to the actual overall feeling of my experience! Furthermore, if I could do as much it would be great as well to consciously change the activity of my brain to re-wire my conscious lived experience.

Like a process of biofeedback?

Exactly!

Er- okay…you are setting the bar rather high…but if you collect it from my assistant in the next couple of weeks I’m sure we’ll have something cooked up for you.

IV

*Andrew bursts through the office door*

Yes! You’ve done it Professor! I can perceive and understand the exact workings of my brain generating this feeling, even as I subjectively feel it! Now, with a bit of effort I can tweak the activity of my hypothalamus to dampen the release of stress hormones-excellent-now I can optimise connectivity in the prefrontal cortex to improve my planning of this biofeedback process itself-soon I will have cognition second to none!

Hmmmm.

Are you okay, Professor? This is tremendous! Why do you seem so negative? Are you worried about me abusing my power?

No, it’s more an intellectual concern. What you’re saying is all well and good, but it just applies for you. Who’s to say that my experience is not generated by different brain processes, or that my subjective states of mind feel the same?

Well Professor, I’m sure that you probably do use your brain in somewhat different ways to me. In terms of how things feel, well, at the same time as the autocerebroscope is showing me in the inner workings of my brain, I can also see the nerves and how they are projecting to and from other parts of the body. Feelings are tied up with a visceral response that extends throughout the body, so I’m sure that even if we did have the exact same types of brains that happened to be wired up and working in exactly the same way, then subjective feelings would still feel different, given differences elsewhere in our bodies.

Yes yes yes, but who’s to say that for some people these workings of the brain feel like anything at all?

……Eh, I don’t know, but surely the fact that it can be the case even for one person is important? This is a clear demonstration that conscious experience is possible without having to appeal to some immaterial ectoplasm-type stuff?

Not necessarily, Allen! It may only produce something that’s conscious experience-or something like consciousness- for you. But not like qualia for most people. Without access to your experience how do I know you’re really linking the brain activity with the bare bones of qualia (as I experience it) or rather with some easy problem like how your brain is processing a particular sensory input, which may anyway be enough for you to count as qualia, but not enough to count as qualia for someone with such depth of feeling as myself?

To me, this seems like a dichotomous, either/or approach to consciousness. Even if your experience is more complex than mine, then surely if I can tell you how the workings of my brain make up my awareness of the world, then that would show that consciousness can be explained by the workings of the brain?

More complex? Andrew, the mere fact that I can engage in more complex information processing and emotion is beside the point. Consciousness is fundamental-that is, it is so simple it cannot be broken down into any simpler parts!

If you’re right, then the only way for you to know is to have the insight into your own brain…why don’t you try the autocerebroscope on yourself Professor, and see what it’s like?

I’m sorry, it gives me a tension headache. Anyway, I have some papers to write up on why human experience is irreducible to brain states.

*Andrew rolls eyes and leaves office with his new toy*

Apology 1: The device pictured is, needless to say, not the mythical final version of the autocerebroscope described in the story below, but rather an electroencephalogram (which reads the neural activity via electrodes-like all current brain imaging technologies, it is quite far from doing what gets described in the latter parts of the story below).

Apology 2: This story is influenced by numerous thinkers I’ve read over the years-sorry I can’t remember all of my influences here to attribute them. Let me know in the comments if anyone stands out as deserving more of a mention here.

Relevant posts:

A review of Dan Dennett's "Intuition Pumps"

Brief thoughts on compassion fatigue

Brooks originally wanted to design the doll so that it cried more and more hysterically until it got what it wanted, but Hasbro said this was unworkable. The doll had to remain at the level of entertainment, rather than become an actual simulation of human life.

Gaby Wood, "Living Dolls"

When a small boy washed up on the coast of Turkey a couple of years ago, a cartoon in Charlie Hebdo provoked a small outcry when it depicted the youth, in a counterfactual universe, growing up to be a man who harasses women (“our” women!). I’m not sure what the original intent of the author was, although it seems like an ironic comment on the racist double standard whereby well-off white lads are given lenient sentences when they actually do commit an assault, but dead Arab boys who have yet to hit puberty are a sad case, but maybe let’s not get TOO upset, because who knows what they'll be like if they grow up. 

Although such prejudices may exaggerate a lack of compassion, many people saw the sadness at an individual level but then simply felt overwhelmed by the scale of the issue. Most people that I know want to have some kind of compassion towards the many unfortunate people out there. However, as individuals we can only do so much while trying to live our own lives successfully. When compassion fatigue sets in, burnout may follow.

Burnout is characterised by an increased cynicism and emotional fatigue, as well as doubts about the value of one's work. Within the helping professions (e.g. counsellors, mental health nurses) occupational burnout is quite prevalent. Furthermore, within these professions burnout should be of particular concern, as it has the potential to quickly affect others; a burnt out psychologist won't offer the same quality of care to a client. Indeed, this is also the case among informal caregivers (e.g. people caring for a relative with dementia); a burnt out family carer is more likely to see their relative go into long-term care outside their own home. To put the impact of burnout in context, the state of the art in this area is still unclear on the distinction between burnout and depression. Perhaps the lack of a consensus on how exactly burnout should be defined doesn't help.

I suspect that a major risk factor for compassion fatigue and burnout is overly high expectations in helping, and perhaps high expectations of the person receiving help. Help offered in a psychological context is rather more complex than the endangerment of a small child's life. No one who seeks help is perfect, and sadly many people engage in self-destructive and self-sabotaging behaviour. When does sympathy give way to frustration, which gives way to apathy? How long does one bang one’s head over the misattributions some people make before one stops trying to point them out? Self-care is important, so is self-awareness, and so too awareness of the other.  

Perhaps there’s something more fundamental underneath all this. Do we want to go beyond compassion and understanding to something deeper? It’s prosaic to say that a display of emotion (e.g. sadness) in another person can make us feel sad in our own way. But can true empathy (feeling what another person feels) truly exist? Or are feelings that appear to be shared simply a simulacrum of what we perceive to be the other person's emotion? The answer is the latter. Each consciousness is private. Will a difficulty in accepting this worsen compassion fatigue?

Related posts

He ain't heavy, he's my carer

The ups and downs of reaching out

From the depths came the form: gut microbiota and brain cells

As I mentioned previously in a recent post, germ-free rodents have given us a greater understanding of the interaction between the brain and the gut, with animals deficient in microbiota displaying altered anxiety-like and social behaviour.

New research (open access research that is!) from the mighty APC Microbiome Institute has indicated alteration in the brains of these animals. Compared to normal control animals, germ-free animals had increased volume of both the amygdala and hippocampus, regions of the brain associated with processing of emotional and stressful stimuli. This was despite the fact that overall brain volume was not changed, suggesting a proportionate increase in regions of the brain associated with the kind of function that is demonstrably impaired in germ-free animals.

The researchers decided to look further, examining not only regions of the brain, but also brain cells. Using previously established methods they were able to categorise the neurons into different classes. They analysed the extent and complexity of dendrites (the branch-like structures at the end of neurons that receive neurochemical input from other neurons). They found more highly developed dendritic material in a number of different types of neurons in the brain regions of interest. It would thus seem that the lack of microbiota is impacting at a more microscopic level within the brain.

The authors point out the regions of the brain in which they found these alterations interact with (among other things) the hypothalamic-pituitary-adrenal axis, which is responsible for hormonal responses to stress. The impact of the microbiota on these specific brain regions are thus likely to impact upon other brain regions, notwithstanding a lack of change in overall brain volume.

The outstanding question is how the gut microbiota has such a striking effect upon the microstructure of the brain. There a number of different candidate explanations. For example, there is evidence that gut bacteria can use nutrients from the diet to produce neurochemicals. However, the process whereby these neurochemials within the gut lead to serious changes in the brain remains (to the best of my knowledge) somewhat of a mystery. Research that brings us closer to solving this problem will no doubt be generating a lot of buzz in the coming years.


Luczynski, P., Whelan, S. O., O'Sullivan, C., Clarke, G., Shanahan, F., Dinan, T. G., & Cryan, J. F. (2016). Adult microbiota‐deficient mice have distinct dendritic morphological changes: differential effects in the amygdala and hippocampus. European Journal of Neuroscience.

(Banner image for this blog post is a detail from Figure 3, Luczynski et al., 2016).

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Wrap you brain with germs