I wanna get technical: notes on writing a systematic review

Just recently I had the pleasure of clicking "submit" on the longest academic paper I have written so far-nearly 30,000 words long. It is a systematic review of cognition and biomarkers of stress in dementia caregivers. It's an important topic, but today I'd like to talk specifically about the method of doing a systematic review and what that entails.

The process of systemically reviewing the literature allows you to take steps to ensure that a review of research literature is not an incomplete or partisan exercise. However, writing a systematic review, particularly a large systematic review, can really take the pleasure out of reading a research article. Interesting discussion sections are raced past when one has over 100 articles from which to extract key methodological details. Here's what you do:

Firstly, one needs to see what literature is out there. After making searches for caregiver stress and a host of stress biomarkers (e.g. cortisol) on a number of research databases, the second reviewer and I found ourselves with circa 4,000 abstracts and titles to look though. Some of these were almost immediately identifiable as not really relevant to the review in question. However, some required a pretty careful reading of the abstract, and about for about 250 we had to look through the full text of the article. For example, we were interested in the impact of dementia caregiving stress on cognition, but it might not be immediately apparent if cognitive assessment was performed on the carers or just the patients with dementia.

Once you've whittled things down to just the articles you want to include in the review, it's time for data extraction. You get an Excel sheet with a whole host of bits of info (e.g. inclusion criteria, sample size, age/gender of the participants, location where the study was run, etc. etc.) and fill in this form for each study. I should say that in the case of this review we had 151 full papers to go through. A mountainous (albeit physically sedentary) task. The second reviewer blasted through the task quite a bit faster than I did-I'm going to assume it's because she is more experienced at conducting systematic reviews, as the alternatives are not so good for my ego.

Anyways, when the data extraction is done you THEN need to assess the quality of the research literature. Another template is put together in an Excel file and again you wade through the articles, ticking boxes about whether or not the articles have fulfilled certain criteria (did they control for potential confounding variables, was the statistical analysis appropriate). In fairness, there's often some overlap here between the data extraction, although not enough in this case to avoid going back through the articles again!

THEN you need to write the thing. When you have results from over 150 research articles to summarise, the mere process of checking the formatting within your tables becomes a dull and onerous task. Uughhhh. Still, when it's finished you can say that you've gone to lengths to avoid being selective in either assessing or reporting the published research in the field.

Obviously this is one account-there are more/less complex ways of doing a systematic review. Generally there will not be quite so many articles included in a systematic review, and if the outcome is more focused one may wish to do a meta-analysis. I think as time goes by more journals will start to strongly encourage or demand that review papers are systematic. All I can say about my near future is the next couple of reviews I write will not be systematic in nature.

If/when the article of this systematic review is published I'll be letting you know about the results ;)

What's it like to be me?

When people use the word "consciousness", they can be referring to many things. At a simple level, they could be referring to being simply awake, or having some awareness of the world. At a more complex level, they could be discussing awareness of one's own self. But there is another thing people talk about when they speak of consciousness-the ineffable sense of what it is like to be oneself. It seems reasonable to most people that the human brain should be capable of dealing with waking, as well as the harder task of thinking about one's own cognition.

However, it is less popular to think that the brain can produce this intangible feeling that we can only really observe in ourselves. Many people believe that this feeling will continue after death has taken our fleshy brain from us. Some people believe that the scientific study of consciousness will progress better if we treat consciousness as a fundamental property, something which cannot be broken down into something simpler, such as the biological and chemical processes underlying brain function (much like electric charge became seen to be a fundamental property in the 19th century,).

However, if our conscious experience really is just the product of our feverish brains, than perhaps the holy grail of neuroscience is to find what it is in the brain that brings this about...

The neural correlate of consciousness!

A cool paper by Naotsugu Tsuchiya and colleagues discusses the search for correlates of consciousness with and without self-report. Self-report can be combined with clever methods used to make the same sensory input, depending on context, available or unavailable to awareness. Continuous flash suppression involves presenting one eye with a flashing stimulus and the other eye with a more constant stimulus. The flashing stimulus can lead to the other stimulus (which, remember, doesn't change) slipping out of consciousness, even though the sensation should still be there.

So let's say you're a research participant being subjected to continuous flash suppression. The experimenters need you to tell them what you're consciously perceiving, in order for them to observe what is happening in your brain as the subjective experience changes. However, in order to self-report on what one perceives, one needs to draw on cognitive processes other than "raw" consciousness. If you have to say what you see, you're using language processing. If you have to press a button when you see the white elephant, you need to use motor processing. Control conditions have to be carefully designed!

So there are a number of caveats about self-report. Methods that do not use self-report are not perfect either though-it's harder to tell whether the thinker is really (self-)aware of the information they're processing. However, what's really neat about a lack of self-report is that it can be applied in contexts where self-report may be difficult or impossible, for example in babies or in animals.

Of course, you might object that much of this is just about the not-so-hard problems of how we are aware or self-aware, not about what consciousness is like. I think this takes us from the methodology we use to study consciousness, to our account of what "ineffable" consciousness is about. Our subjective sense of what experience is like involves combining a wide variety of sensory inputs (not to mention memories, body schemas etc. etc.) into a unitary experience. The binding problem poses the question of how we perceive our experience as a unified stream of consciousness.When we talk of a "neural correlate of consciousness" it's probably too simple to think that one part of the brain can "bring it all together". In order to integrate various sensory inputs together we have to combine sensory processing occurring in distinct regions of the brain. Gerald Edelman has suggested that the thalamus plays a key role, as it carries information from the senses to various parts of the cortex. It is the re-entrant nature of these connections that may help to explain the process (as opposed to the place) where experience comes together to make up a unitary sense of consciousness.

You may hold fast to the idea that your experience cannot be just the product of your brain (and its interaction with the rest of your body). But if so, let me pose this question: just how complex is your conscious experience really? Are you sure it is more complex than the interactions of the trillions of neurons in your brain? If you or someone else really understood how it all worked, are you so confident that they might not be able to explain your lived experience, with no need to discuss anything outside the biological and chemical processes within you?


Tsuchiya, N., et al. (2015). No-report paradigms: extracting the true neural correlates of consciousness. Trends in Cognitive Sciences, 19(12), 757-770.


Related post
Where does the mind begin and end?
A review of "Intuition pumps" by Daniel Dennett

Pay attention

I tried to read my school books despite the fact that my mind wandered a thousand miles away. I would come back to whatever I had been reading wondering to myself where I had been for the last five or ten minutes. It was not that I could not remember what I had read. Rather, I had never read the page I was staring at for that period of time. (Allan Schwartz, 2007)

This account of ADHD is something most people can identify with to some extent. Going over a lecture on attention for a neuroscience module at UCC, I'm thinking again about sustained attention. What can neuroscience tell us about how we focus our minds on a particular stream of information?

In studying sustained attention, a typical experimental task will ask participants to attend to a fairly boring set of stimuli for a prolonged time and produce a periodic response to an occasional target stimulus (e.g. a repetition of a number in a series of generally non-repeating numbers). Cognitive psychology giant Michael Posner and colleagues have suggested that the right cortex is key for this form of attention. However, other research has suggested that when a target is less salient (which made the task more difficult), activation was bilateral (i.e. activation occurred on both sides of the brain). It's a reminder that the nature of a task is key in the brain activity involved. Indeed, given that sustaining attention to such a task becomes more difficult as time goes by, the same task becomes a more difficult job over time within the same person. 

Isn't it almost redundant to say you need motivation to sustain attention on something? If something is interesting then it's inherently motivating to attend to it, but if it's boring you need something to threaten/entice you into attending to it. Given its influence on the reward system, it has been suggested that dopamine may influence sustained attention through its impact on motivation. Methylphenidate (often sold under brand name “Ritalin”) is used in the treatment of ADHD, and it is used to increase the extracellular level of dopamine. Speaking of dopamine-our familiar friend caffeine, which enhances dopamine, has been shown to enhance subjective alertness and improved sustained attention performance on a simulated driving task. 

However, as most people consume caffeine, experimental control is required to ensure that any effects are not due to withdrawal reversal. If you want to run a study on caffeine effects, you can ask people taking part to avoid caffeine for long enough before a study for any caffeine to have left the body. So now you can say that if you give 200mg of caffeine it's not being added to another 200mg the person drank an hour ago. However, long enough to get caffeine out of the system is not necessarily long enough for withdrawal symptoms to have passed. So there is a risk that the enhancing effects are only shown because you give a person caffeine when they are withdrawn. I should note that there has been some debate about the extent to which withdrawal reversal has confounded research on caffeine, including evidence to the contrary. 

Evidence for a role for noradrenalin comes from the spontaneously hypertensive rat (SHR). As the name suggests, it is prone to high blood pressure. However, it can also act as a model of ADHD-although it has its critics, this type of rat has been shown to demonstrate a number of traits associated ADHD (including impulsiveness as well as inattention). Noradrenalin has been implicated in the ADHD-like behavior of this rat by the alteration of such behavior by the noradrenergic drug Guanfacine. 

I can close with a quick tip on sustaining attention, as someone who has had his mind drift far away at many a lecture. When I decide I really need to focus on a talk, I try to think of a question as early on as possible in the talk. I then try to see if anything in the talk answers this question. Whether or not I will actually ask the speaker this question aloud, I imagine that I will have to ask it, and thus motivate myself not to look foolish by asking a question that has been answered by the content of the talk. I don't have any great solution for when one is sleep-deprived and heavily sleepy though-suggestions welcome!

Related posts:

Mindfulness and the mind

Conference review, Part 2: APS Young Investigator Colloquium

The Young Investigator Colloquium is a satellite event for the American Psychosomatic Society Meeting. The aim is to bring 25 young investigators together with 10 senior researchers to receive mentorship about their research ideas. As a participant at this year’s colloquium, I am a member of the Engel group, with Susan Lutgendorf and Redford Williams as mentors.

Young investigators present their research ideas for 5 minutes. This is followed by 15 minutes of feedback from mentors and then 10 minutes of feedback from the other young investigators. This pretty much inverts the usual ratio of presentation:feedback within a talk. It's a nice way to take the focus of rehearsing your speech about what you know already and bring the focus to getting more perspectives on how your work could be different. 

One point that was brought up across the board was the potential to incorporate genetics into our work. In the research I work on, we already have plans to look at the genetics of the microbiota, although perhaps the human genome is something I have dragged my heels about learning about. Another suggestion was to make better use of models in writing grant proposals (you can’t go too wrong with more boxes with arrows). I suppose it does no harm to get a review written before asking for money for research, so you can include your article’s figure as well for a cheeky self-citation. The peer review was also mutually beneficial-we discussed topics such as trade-offs between using double-blind design and completing a trial quickly if placebos take a long time to produce, employing mixed methods with qualitative methods and chasing different sources of funding.

When many conferences are talk-poster-talk-sponsor table-talk, it is forward-thinking to have a more active learning activity like this, not to mention generous of mentors to give up half a day for the event. I don’t think my project will undergo a sea change as a result of the Colloquium. However, I don't this was really the aim; one of the objectives was to improve the writing of our research proposals, as well as critiquing the research ideas themselves. It does seem a pity that close collaborations between people in our group didn’t seem to suggest themselves by the end of the half day, but then there was a diversity in our research topics as well as underlying similarities. Later in the conference we were treated to lunch with the mentors. It was a good chance for the organisers to plug next year's meeting. Given that it will be at the closer venue of Seville Spain, and as Colloquium participants get free registration for the following year, I'm inclined towards attending.

 Related posts:

APS conference review 

Conference review part 1: American Psychosomatic Society Meeting 2016

Weclome to downtown Denver, where the buildings are tall and the wide roads full of clean young cars and pick-up trucks. It's the American Psychosomatic Society meeting 2016, and I had a tube of three posters to present, all of which can be downloaded in full from the UCC psychiatry website. Despite the relatively late timing of the poster session it had a very lively atmosphere.

Dean Ornish gave a great talk on how common-sense behavioural intervention (comprising diet, exercise, stress reduction and social support) can not only be a part of preventative medicine but also have startling value in treating various chronic health conditions, including cancer as well as heart disease.

His talk was followed by Lisa March, who highlighted how mobile technology can be used to implement the kinds of program that Dean Ornish had just been discussing. I liked her term of "minimally disruptive healthcare", capturing the idea of how the process of receiving treatment may be burdensome for some patients.

A symposium on mindfulness generated some interesting topics-Eric Garland highlighted how mindfulness is often defined more in terms of what it is not (e.g. non-judgmental) than what it is, although he suggested that positive re-framing (quite CBT-ish) could be what it is about, as well as savouring (so perhaps increasing positive feelings is as important as reducing stress). Jeffrey Gresson and Linda Carlson also gave interesting talks on mindfulness for stress reduction and psychological recovery from cancer. In both their talks the concept of spirituality was brought up. The spirituality measures they used seemed to differ quite a bit, although frankly I think this is symptomatic of the incoherence of spirituality as a concept.

Speaking of mindfulness, the meeting also had regular well-being classes, including mindfulness and tai chi (I must confess I didn't attend these, given a mix of familiarity with many of the topics plus schedule clashes). It's great that the conference can have these types of events as part of the program, in addition to the awesome Young Investigator Colloquium (covered in depth in an upcoming post).

Saturday morning saw prize presentations from three major researchers. Following a hagiography of an introduction from one of his mentees, brain-gut axis demigod Emeran Mayer took to the stage. He presented some well-known work from the last couple of years on probiotics and fMRI, as well as broader characterisation of the microbiota. Some newer stuff highlighted his more recent work with Jennifer Labus using mathematical models to link a variety of variables at the levels of psychological report, neuroimaging and microbiota across multiple pathways (it looks a bit like structural equation modelling, although as he didn’t have scope to get into great depth; there may be more to it than that). Even if it is just SEM it’s probably an underused method for mapping the complexity of brain-gut interactions.

George Slavich discussed STRAIN, a stress questionnaire that takes about 20 minutes to fill in, thereby giving more detailed information than something like a 10-item scale, but more do-able than some of the deeply in-depth life stress interviews which can take hours to analyse. Professor Liz Brondolo highlighted her work on racial discrimination and its negative psychological impact, with a particular focus on how it may moderate the clinician/client relationship. She employed an intuitive case-study type structure to make some of the issues she highlighted more concrete (e.g. physical fatigue enhancing fatalism around health, social cognition around subtle conversational cues leading to better/worse communication between clinician and client).

I had a little time for some tourist stuff as well, including sampling some local brews, as well as a pre-conference visit to the natural beauty of Red Rocks. All in all a good time! (Credit to significant other Daniela Scevaroli for the picture below).

Doctors on the brain:National Neuroscience Curriculum Initiative

There's an old adage that neurologists know what’s wrong but can’t treat it, psychiatrists can treat it but don’t know what’s wrong. Many feel that neuroscience is under-represented in the training of doctors who wish to specialise in psychiatry. A psychiatrist colleague (and a major fan of former National Institute of Mental Health director Thomas Insel) pointed out an initiative that may go some way to addressing this shortfall; the National Neuroscience Curriculum Initiative.

This is an NIH (National Institute of Health, USA) collaboration between educators & neuroscientists. The aim is clear: to enhance neuroscience education for doctors specialising in psychiatry, so they integrate modern neuroscience into clinical practice. There is an expressed focus on interaction between environmental stressors and neural circuitry. Some of the more basic content one would hope would be covered in training any psychiatrist (e.g. anatomy of the brain) but the use of 3D layout may put the material across in a more intuitive and easy-to-learn manner. I can imagine the modules on neuroscience in the media being enjoyable for students (especially material the microbiome although I'm biased in this regard). However, I would imagine that it will be the integrative case conferences that will really push trainee psychiatrists to think of ways to put neuroscience into their clinical practice.

It seems like an open endeavour-there is an invite on the website to contribute content (although it is peer reviewed and one is not guaranteed publication). Facilitators (who should be members of faculty) are required for much of the work involved, so I don't think one can simply stroll onto the website unaccompanied and run the course in full by oneself. 

One would hope that training programs who would benefit from this initiative will make the most of it. However, given the prevalence of reduced sleep and associated negative effects amongst junior doctors, one can imagine that such a course would have to compete with other training and development demands placed upon these doctors (not to mention their clinical work).

The initiative also has an associated meeting: the Brain conference is just a few short days away in Austin Texas. It will focus on improving teaching skills within neuroscience and translating them to clinical practice. I won't be in attendance for this (I'm not a clinician, after all), but I will be going to the American Psychosomatic Society meeting in Denver, Colorado-more on this next month!

Shoot that Freudian arrow through my heart: Psychology of love

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Okay, I haven't actually become a pick-up artist consultant just yet. The interwebs is awash with fedora'd gents and bitter females seeking the trick to capture the physical and sexual attraction of their object(s) of affection. The science of human behaviour is often invoked/called upon in this quest-but how much have we learnt empirically about love?

Robert Sternberg proposed a triangular theory of love, involving three different factors which can be more/less apparent in different manifestations of love. Let's look at each:

Intimacy
Feelings of closeness and bonding-one can of course experience this with Platonic friends as well as romantic interests. Sadly, there does appear to be a lack of psychological investigation into the highest form of love (I am, of course, referring to the bromance). However, Platonic relationships between heterosexual, opposite-sex dyads has received some interest. There are multiple reasons why people may choose to remain "just" friends other than a lack of attraction-perhaps the most interesting to me is "risk aversion", a term which invokes all kinds of ideas to be imported from behavioural economics (not that we should apply the principles of economics to the study of love, cough cough).

Generally, when people talk about "lovers" they are referring not only to people who are intimate, but who also share...

Passion
Perhaps the aspect of love most associated with Valentine's day-physical attraction. Not surprisingly, sexual motivation and behaviour differs in its role within relationships as relationships develop. The early phase of romantic love is probably most associated with this aspect of love. Interestingly, it seems that people in the early throes of love have reduced production of cortisol, a hormone associated with stress. (Seems a bit counter-intuitive, given that one can be on one's toes quite a bit in the first few months, but there's the data for ya).

Of course, mismatches in sexual behaviour can lead to relationships tripping at a first hurdle. Nonetheless, many relationships seem to stay the course even if a couple have divergent sex drives. An interesting recent study indicated that attachment may play a role. New couples were followed over a number of months. People with ambivalent attitudes towards sex had low relationship satisfaction early in the relationship, but this only persisted at follow-up if their partners were high in avoidant attachment. In other words, there's a higher risk things will fall apart if your significant other is highly insecure.

.....

Sorry, just having a flashback there. Let's move on...

Commitment
Some relationships characterised by both passion and intimacy may fizzle out relatively quickly. However, with commitment, decisions are made concerning the persistence of the relationship now and into the future, as well as decisions about exclusivity (for most Westerners). At a deeper level, there is commitment to help the other party out if they need us-this is perhaps most strongly visible where one person becomes sick, particularly in the stark case of dementia.

Our relationships don't exist in a social or cultural vacuuum- An interesting study found that people in marginalised relationships invested less in the relationship, yet were more committed to it. (One might have made the a priori assumption that marginalised couples would invest more as well as feeling more committed). The authors defined "marginalised" relationship as same-sex couples, interracial couples and those with an age gap of greater than 10 years (although one would imagine that overall age of the partners as well as which one is the older one would moderate the perception of the whole age difference thing). It was nice to see that "marginalised" couples reported a similar level of overall relationship satisfaction however.

I think the psychology has given us some interesting and at times counter-intuitive insights into relationships, although I don't we've really unlocked the key to winning the heart of whoever you choose just yet. Anyways, if things don't work out in the long run, there is evidence that divorced people report higher life satisfaction than those who have never married, perhaps due to differences in self-esteem. Better to have loved and lost...