Monthly Archives: September 2009

Review: Review Article on Cognitive Dysfunction in Multiple Sclerosis

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The featured paper is ‘Cognition in Multiple Sclerosis: A Review of Neuropsychological and fMRI Research’ by Genova and colleagues. As the title suggests the authors examine the characteristics of cognition in Multiple Sclerosis. I could not identify a stated methodology. However the authors cite 140 papers throughout the paper which is reflected in both the breadth and depth of  relevant material covered. Broadly speaking the paper is divided into a section on neuropsychological profiles and another on the findings in functional MRI studies. In terms of neuropsychological profiling, the authors cover constructs ranging from working memory through to fatigue. They focus on the relationship of processing speed to a number of other constructs and suggest that clarifying this relationship further would be an important aim for future research as it would have implications for therapeutic strategies. Essentially if processing speed impacts on working memory and complex task completion then research in this area would be expected to inform therapeutic strategies. On the other hand, if there are confounders then they suggest that this would necessitate multiple treatment approaches. The authors explain a number of concepts as they cover material and I found this quite helpful. I find that this approach works really well in review articles and more so in those that cover many domains. With regards to fMRI studies, the authors emphasise the neuropsychology. Again their arguments are easier to follow as the article is to some extent self-contained allowing referencing to previously explained concepts. The authors draw attention to some of the conflicting findings in the field and the reader is able to use this information to facilitate selection and interpretation of future studies in this area.

The authors have written a clear exposition of the subject, carefully explaining important concepts and leaving the impression that the subject has been comprehensively covered in the neuropsychological domain. The relevance of processing speed to cognitive dysfunction looks to be one of the big questions in this field at the moment.

References

Genova H M, Sumowksi J F, Chiaravalloti N, Voelbel G T and DeLuca J. Cognition in multiple sclerosis: a review of neuropsychological and fMRI research.

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You can listen to this post on Odiogo by clicking on this link (there may be a small delay between publishing of the blog article and the availability of the podcast).

Responses

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Disclaimer

The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog

Index

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Review: Frontal-Subcortical Dementias

Model Brain

The article reviewed here is itself a review article ‘Frontal-Subcortical Dementias’ by Raphael Bonelli and Jeffrey L Cummings. Cummings is a prominent figure in the field of Subcortical Dementia and has edited a book on the subject. This article is what I would term an expert review. Although there is no stated methodology there is a carefully considered overview of the field with the authors demonstrating a deep understanding of the field. They argue for the existence of a frontal-subcortical dementia. Thus they group an extensive list of conditions under this heading for the purpose of identifying common clinical features. While the section on anatomical circuits of frontal-subcortical dementia is useful, I found the discussion of neuropsychological features in the frontal-subcortical dementias to be particularly interesting. One of the tables in the paper covers ‘contrasting characteristics of cortical and frontal-subcortical dementia syndromes’ and distills a lot of material into an easily understandable format. The two types of dementia are contrasted in domains such as memory, visuospatial skills, calculation and mood. Even the simple presentation of the material in this way offers the reader a new perspective on a heterogenous conditions which they demonstrate have just as many shared properties as they do differences. The concept of a frontal-subcortical dementia may become more influential and it will be interesting to see how this develops.

References

Raphael Bonelli and Jeffrey L Cummings. Frontal-Subcortical Dementias. Review Article. The Neurologist. Vol 14. Number 2. 2008. 100-107.

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Disclaimer

The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog

News Round-Up: September 2009 4th Edition

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Research on Antidepressants

The British Journal of Psychiatry features two interesting studies on antidepressants. The first features a patient rating scale for antidepressant side-effects – the Antidepressant Side-Effect Checklist (AEC) which is included in the Appendix for the paper (Uher et al, 2009). The researchers compared this patient rating scale with a clinician rating-scale, the UKU in 811 subjects with depression who were participating in an open-label trial comparing Nortriptylline with Escitalopram. The Nortriptylline was included because of a strong affinity for noradrenergic receptors (it would have been interesting to see whether similar findings would have occurred with Reboxetine). They found that after correcting for the severity of depression, the AEC scores predicted discontinuation of escitalopram (although curiously not the Nortriptylline) and validated the use of the instrument for the purposes of establishing side-effects in antidepressants. In another study, this time qualitative, the researchers explored the emotional side-effects of the SSRI’s. The responses from the participants were grouped into 7 categories and there were many interesting comments from the participants (Price et al, 2009). Both a reduction in ‘positive’ and ‘negative’ emotions were reported and there was some supporting evidence from an analysis of comments on several depression related online forums. The authors suggest further quantitative studies to investigate the findings from this study.

Financial Skills and Risk of Dementia

Predicting which people with Mild Cognitive Impairment go on to develop dementia is an area of current research interest. There are many studies using different methodologies looking into this question. One predictor is that the size of the Hippocampus (size is inversely correlated with dementia risk) which has a robust evidence base. However, a recent study provides evidence that financial skills may be another marker of risk and this has been widely reported in the media (e.g. here, here and here). A research team, just published in ‘Neurology’ found that people with Amnestic Mild Cognitive Impairment who scored poorly on the Financial Capacity Instrument were more likely to develop dementia. The sample group were people with Amnestic MCI and are therefore already a select group who have been assessed as having formal difficulties with memory. They were being scored on a tool which measures financial skills. The size of the study is relatively small (n=163) and of these, 25 people with Amnestic MCI went on to develop dementia.

Blog Round-Up

Just to mention that the dead salmon study is generating a buzz in the blogosphere. The question is why the salmon’s brain activity showed up on the fMRI scan. Three issues affecting the interpretation of fMRI data are described in Developing Intelligence’s article – multiple comparisons, cluster comparisons and independence of multiple tests. For the interested reader, the pdf of the poster is located here. The authors presented the salmon with photographs followed by a ‘rest’ period and then analysed the change in BOLD signals in voxels. They performed one analysis without corrections. This ‘revealed’ a region of activity in the Salmon’s brain. They then carried out two types of comparison that are routinely used in the analysis of fMRI data using software packages such as SPM2. These corrections are necessary because if there is ‘random noise’ then some voxels should be firing above the threshold level just by chance. Thus you need to correct for both the combination of chance and the large number of voxels that are being examined. The two methods that are routinely used and included as a default in one statistical package are family wise error rate correction and false discovery rate correction.The debate that is currently taking place revolves around some posts which have likened these results to those of another study originally called ‘Voodoo Correlations in Social Neuroscience’ (reviewed here) and provoking much scandal before it surreptitiously changed its name to ‘Puzzling High Correlations in fMRI Studies of Emotion, Personality and Social Cognition’ (reviewed here). The point made in the Developing Intelligence article is that the ‘Voodoo Correlations in Social Neuroscience’ paper focused on independent tests whereas this paper focuses on multiple comparisons and thus a number of bloggers have misrepresented the paper. I would argue that both sides are probably right. Thus (and at the risk of sounding slightly pedantic), the Voodoo/Puzzling paper takes a broad swipe at fMRI study methodology from the statistical analysis right the way through to the way in which the analysis is presented within the papers. Thus

1. They do explicitly at one point, mention within-subject comparisons (i.e. changes occuring between tasks in the same subject)

2. In the second part of the discussion, the authors specifically ask the rhetorical question

‘Is the problem being discussed here anything different than the well known problem of multiple comparisons raising the probability of false alarms?’

In their response, the authors state that ‘The problem we describe arises when authors then report secondary statistics on the data in the voxels that were selected originally‘ before then adding ‘In the case discussed in this article, correlations are both the selection criterion and the secondary statistic‘.

3. However, most telling is Vul et al’s response to the responses to their original paper (available here) where they state explicitly that

6. We pointed out that although most studies used appropriate multiple comparison corrections (and thus identified voxels that do indeed have nonzero correlations), these methods are not always correctly applied, even in articles that have passed peer review’

One salmon tries to leap over a large waterfall while the other jumps into a hungry bear's mouth

One salmon tries to leap over a large waterfall while the other jumps into a hungry bear's mouth

However, taking the study a little further in a slightly tongue-in-cheek fashion, one interesting question to ask is

‘Why was any activity being picked up at all?’

The fMRI scan typically picks up oxygenated-Haemoglobin and it is the change in oxygentation of the Haemoglobin with delivery to the brain tissue that produces the signal. So if the Salmon was dead, we could safely assume that there was neither blood flow nor any delivery of oxygen to the brain tissue. So where is the change coming from? Well, I thought there was something fishy going on here and I was unsurprised to find a paper on the analysis of Salmon blood (freely available here). After looking very briefly at this paper, it appears the researchers in the fMRI study have omitted some crucial details for the interpretation of the data. Thus we do not know if their selected Atlantic Salmon was caught in fresh water or bracken water, as the corresponding temperatures would affect the oxygen dissociation curves of the salmon’s haemoglobin. We also need further information on the temperature of the room at the time of the scanning as well as the period of time for which the salmon had been deceased.

There is one possible explanation for the BOLD signals. They could represent a dissociation of the oxygen from the Haemoglobin with time. When the dissociation occurs, the magnetic properties of the Haemoglobin are altered and this will be picked up by the MRI scanner (oxygenated Haemoglobin is diamagnetic and deoxygenated Haemoglobin is paramagnetic). On moving from the presentation of the photographs through to the rest period there may be a continuing dissociation of oxygen from the Haemoglobin and it is this which is being picked up by the scanner. More interesting (and a very remote possibility) is that the authors of the poster have picked up deoxgenation in the Salmon’s Substantia Nigra, a region which is associated with Parkinson’s Disease in humans. The reason I mention this region is two-fold. Firstly, on the admittedly low resolution image of the Salmon’s brain on the poster, in the sagittal section, the activity is located close to the spinal cord and may therefore correspond to the midbrain (although I know next to nothing about Salmon neuroanatomy. I did however find a reference to the Substantia Nigra in Salmon). Secondly, in humans at least, the Substantia Nigra contains Haemoglobin which may offer it some protection during periods of anoxia and which also gives it the has a characteristic dark stained appearance (hence the name Substantia Nigra*). Salmon do a lot of moving about (as in the above picture) and the Substantia Nigra is involved in the regulation of movement. However against this hypothesis, the corrections in the statistical analysis eliminated the activation patterns, and there were at least two areas of activation in the uncorrected analysis.

Human Substantia Nigra - From Gray's Anatomy 20th Edition

Human Substantia Nigra - From Gray's Anatomy 20th Edition

So in summary, there’s a remote possibility that the imaging study was picking up the dissociation of oxygen from Haemoglobin in the Salmon’s Substantia Nigra post-mortem or as they infer, the activity was due to their incomplete analysis (particularly as the differences disappeared after the necessary corrections were made).

* The characteristic dark appearance of the substantia nigra is from the melanin in dopaminergic neurons.

Addendum

There may be another explanation for the findings. Thus if there is a mix of red blood cells (RBC) of varying levels of oxgenation, then the scanner may causes a realignment of the RBC’s according to their magnetic properties. If the magnetic field is applied as a pulse, then there will be further realignments when the magnetic field is changing. This may produce eddy currents, in which the Haemoglobin generates a reactionary magnetic field which will then ‘resist’ the next pulse of the scanner. If this were the case, it means that Haemoglobin molecules would undergo a more marked change in alignment during the initial part of the scan and this might explain the difference.

On a slightly different note, the brightest light in the known universe – the Diamond Light Synchrotron (see Podcast review here) is being used to examine iron deposits in Alzheimer’s Disease and together with the finding of Haemoglobin in the Substantia Nigra A9 cells, this is a very current area of research.

Addendum (4.10.9)

See the comment below from the author of the poster – Craig Bennett (also author of the blog at prefrontal.org) on the interpretation of the results.

References

Price J et al. Emotional side-effects of selective serotonin reuptake inhibitors: qualitative study. The British Journal of Psychiatry. 2009. Vol 195. No 3. 211-217.

Uher R et al. Adverse reactions to antidepressants. The British Journal of Psychiatry. 2009. Vol 195. No 3. 202-210.

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You can listen to this post on Odiogo by clicking on this link (there may be a small delay between publishing of the blog article and the availability of the podcast).

Responses

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Disclaimer

The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog

Podcast Review: September 2009. 3rd Edition – August 2009. Nature Neuropod.

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The podcast reviewed here is Nature Neuropod – August 2009 edition featuring Kerri Smith. The sounds quality is very good as would be expected from a Nature production. I couldn’t hear any background noise (e.g. clicks) and the dialogue is very clear and features interviews with neuroscientists. The podcast can are also displayed in segments, so that you can play individual parts of interest rather than listening to the entire podcast.

The August edition features an interview with a members of a team that is constructing a multimodal map of the brain. They have significant ambitions to replace Brodman’s map with something far more sophisticated and which will superimpose neurotransmitter data and fMRI to produce what they describe as a ‘Google Map’ and presumably means that information on different brain regions will be easier to locate. Mind Hacks also covers the podcast here. An intriguing post looks at ‘jumping genes’ or transposons/retrotransposons in the hippocampus. The transposons are genes that move about within the genome and are thought to be drivers of evolution. For instance in this Science Daily article there is a report on research into grapevine transposons and a comment on how they might have impact on genetic diversity.

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In the Neuropodcast there is also a look  at a study of synaptic formation in the retina. In the study, the researchers challenge the notion that competition is required for shaping synapses between bipolar cells in the retina and offer a potentially new paradigm for synaptic formation.

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Disclaimer

The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog

Blog Review: The New Social Workers Blog

 

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The blog reviewed here is ‘The New Social Workers Blog‘  which is a companion to a free American online quarterly magazine ‘The New Social Worker‘ a magazine written for social worker students and recent graduates. 

In terms of the presentation, the title pane is a white on blue background. The general background is a light green colour while the posts contain black text on a white background. At the bottom of the main pane, there is a Blog Archive which indexes articles according to the month they were posted. At the time of writing there are two right-hand panes. The first has a green background and contains links to sites related to the blog and magazine. The second, lower pane has a white background and links to the twitter account for the New Social Workers, as well as containing links to the blog authors, followers, a blog-roll and the RSS feed. The blog archive dates back to 2008.

The first post is written by Ms T.J who has written almost all the blog articles and here explains that she is doing a full-time Masters in social work. Ms T.J writes about her experiences both on the social work course and in her own life. We hear about the sad deaths of a number of her close friends, the completion of course work assignments, Ms T.J’s other role as a writer for a magazine amongst many other postings. 

Here are just a few of the posts (and links) I liked

A post about National Social Work Month. This got me thinking. Maybe there’s a place for a National Psychiatry Day!

A post about the use of technology in social work with some comments about how web technology is already making an impact.

How the Homeless stay connected online. A post about a homeless man who runs an online forum as well as maintaining a significant online presence while sleeping under a bridge!

A link to this article on some ways in which technology is impacting on social work.

The ‘New Social Workers Blog’ gives the reader an insight into the experiences of  an American social work student and it will be interesting to see how the blog progresses with the course that Ms T.J is undertaking. 

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Disclaimer

The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog

Book Review: One Nation Under Therapy

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The audiobook reviewed here is ‘One Nation Under Therapy (Unabridged)’ by Christina Hoff Sommers and Sally Satel and narrated by Dianna Dorman. Dorman narrates clearly and with expression. I found that the narration made the material easy to listen to and helped to keep my attention focused.

As I wasn’t familiar with the authors before listening to this book I performed a quick Google search. Christina Hoff Sommers has been a Professor of Philosophy and has a Wikipedia article (a.k.a internet biography) which covers some of her other works as well as her views on gender and equity feminism. These views have apparently provoked much discussion. Dr Sally Sattell is a psychiatrist who is also widely published and amongst her other works is a look at political correctness in medicine. Sattell also has a Wikipedia article.

I found the content very interesting. Some of the material might be considered controversial but it can be argued that such dialogue is necessary as it facilitates reflection on and appraisal of practice. The authors focus on a number of issues relating to therapeutic intervention. One of the themes they explore is that of vulnerability of children. Thus they argue that children in schools are being increasingly ‘cushioned’, for instance being given less homework or parents responding to PE lessons that are considered too difficult. The authors are referring to the American schooling system in their work although it can be argued that it can be difficult to generalise as there will be heterogeneity not only between schools but also between pupils within the same school.

They also discuss how bereavement theories developed by Colin Murray Parkes, John Bowlby and Elizabeth Kubler-Ross (‘On Death and Dying‘) have been misinterpreted and also refer to Freud’s Mourning and Melancholia. Thus they argue that following bereavement, the bereaved will not necessarily follow a strict phases but that there will be considerable variation between individuals and that abnormal’ bereavement necessitating treatment occurs in a relatively small percentage of the bereaved (see also this review on Art Therapy and Bereavement). They also comment on what they describe as a movement towards providing counselling in those that have been recently bereaved despite the above although again this may be too fluid and heterogenous to characterise.

During the discussion of Post-Traumatic Stress Disorder there are many references to British Psychiatry including Professor Simon Wessely and an interesting quote from Aubrey Lewis who noted that the number of new cases of neurosis did not seem to increase during the Blitz in Britain. They consider the origins of PTSD in detail and look at some of the issues in the empirical research. They consider situations in which treatment for traumatic experiences is not warranted.

The term they use through the book is that of therapism, which is a movement they trace to therapists such as Carl Rodgers. They consider historical aspects of the origins of the person-centred movement that filled the gap created by the decline in the popularity of psychoanalytic psychotherapy. They argue that some of the values found within this movement have permeated society through various educational programs and that this perspective can create difficulties in establishing moral responsibility.

The authors raise many issues in an uncompromising and engaging style and this is a work which may continue to provoke much needed discussion.

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Disclaimer

The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog