Are the properties of the Neural Substrate for Attention Highly Heritable?

There’s an open-access paper by Fan and colleagues titled ‘Assessing the heritability of attentional networks’ which is available here. The researchers provide a background to the research in attention networks. For the purposes of this study the researchers are interested in three specific attentional networks

1. The orienting network which involves orientation towards a stimulus of interest. They detail some of the suspected neural correlates and associate this with the cholinergic system.

2. The executive network which is ‘resolving conflict between stimuli and responses’. The researchers identify some of the likely neural correlates and associate this network with dopamine.

3. The alerting network which ‘maintains the alert state’. Again the researchers identify the likely neural correlates and associate this network with noradrenaline.

They then provide a lot of good evidence to suggest that these networks can be associated with different mental illnesses and that there are good arguments for supposing that the properties of these networks should be highly heritable.

In their study design, the researchers have recruited monozygotic and dizygotic twins. In brief, the participants undertake neuropsychological tests which assess attentional responses. These are described in more detail in the materials and methods section. Dizygotic twin performances are then compared with those of monozygotic twins in order to better understand the genetic load of these networks.

One of the thoughts I had about this was the difficulty there is in reducing complex mental phenomena to simple models. This applies not just here but to many areas in the clinical neurosciences. Implicit in the models described above is that orienting responses are restricted in some way to a few regions in the brain and that there is a straightforward relationship with acetylcholine. Nevertheless a cursory examination of these assumptions reveals that these regions are interconnected with yet more regions. If you have a massively interconnected structure where is the justification for demarcating regions of function? Such justifications suggest a dichotomous function/non-function scenario whereas the truth might lie along the lines of a continuum with additional regions being recruited as necessary.

However such objections don’t offer a solution in place of the current approach. Indeed with this approach it is possible at least to get things wrong and it is through this act of getting things wrong that a better approximation to nature can be reached (although this might be another tenuous assumption). Nevertheless even if the entire model is invalid, the psychological phenomenon still remain valid but in the process a language has been developed. It is this language which is the important byproduct of the process because it enables the research community to formulate new more meaningful models and this specialised language would fit into what Kuhn describes as part of ‘normal science‘.

After the interesting build up in the paper, in their analysis the researchers suggest the study is underpowered and based on their calculations identify a suitable size for a replication study.

Index: An index of the site can be found here. The page contains links to all of the articles in the blog in chronological order. Twitter: You can follow ‘The Amazing World of Psychiatry’ Twitter by clicking on this link. Podcast: 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). It is available for a limited period. TAWOP Channel: You can follow the TAWOP Channel on YouTube by clicking on this link. Responses: If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk. 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.

Acetylcholinergic Deficit in Alzheimer’s Disease and Treatment

There is an open-access (creative commons attribution License 2.0) article by Cummings and Sabbagh titled ‘Progressive Cholinergic Decline in Alzheimer’s Disease: Consideration for Treatment with Donepezil 23 mg in patients with moderate to severe symptomatology’ available here. In the article, the authors look at some of the evidence suggesting an acetylcholinergic deficit in Alzheimer’s Disease and examine the dose effect of the acetylcholinesterase inhibitor Donepezil. There is a nice quote about the pragmatics of focusing on acetylcholine rather than Amyloid:-

‘The cholinergic abnormalities seen in AD are not viewed as the cause of the disorder, but cholinergic involvement is significant because it is universal, correlates with cognitive defects, and is one of the few pathophysiologic phenomena that can be addressed with currently approved treatment options‘

The authors go on to summarise some of the data on Donepezil at the two main doses including one study supporting a dose effect in advanced dementia without evidence of a statistically significant difference in adverse events between doses. The authors also discuss the FDA approval of a higher dose of Donepezil as per the title although this will be significant for the USA. They discuss the evidence supporting a theoretical justification of a higher dose and specifically focus on the reduction in Acetylcholinesterase inhibition. The main part of the article focuses on a discussion of a 24-week randomised double-blind trial of Donepezil at 23 mg in people with advanced dementia. This study was part of the data set that the FDA reviewed in their assessment and in which it was thus contextualised. The analysis is brief and it would be interesting to know which outcomes were selected in the trial design and what the results were for all of these outcomes. Another interesting point is about the difference in discontinuation rates. In addition is a more detailed exploration of the physiological function of the acetylcholinesterase inhibitors in the CNS. It will be interesting to follow further research in this area.

Index: An index of the site can be found here. The page contains links to all of the articles in the blog in chronological order. Twitter: You can follow ‘The Amazing World of Psychiatry’ Twitter by clicking on this link. Podcast: 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). It is available for a limited period. TAWOP Channel: You can follow the TAWOP Channel on YouTube by clicking on this link. Responses: If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk. 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: March 2011 3rd Edition

Dementia

There is a write-up of the 2011 International Conference on Alzheimer’s and Parkinson’s Disease in Barcelona at the Alzheimer’s Research Forum. Feedback from the conference includes a more critical discussion of the Amyloid hypothesis as well as a consideration of multimodal therapeutic approaches. There was a post-mortem study comparing brains of 4 people with Down Syndrome (average age 66) with 6 controls (average age 70). As Down Syndrome is associated with age related degenerative changes, this study was able to provide useful information in describing age related changes more accurately. The researchers were interested in the number of glial and neuronal cells in the neocortex in both groups using stereological analysis which means estimating 3-dimensional information about the brain from 2-dimensional microscopic slices. Based on their analysis the researchers estimated that in the brains of the sample group with Down Syndrome there were 30% less glial cells and 40% less neuronal cells than in the control group. Interestingly there were similar numbers of cells in the Basal Ganglia in both groups. This may represent a combination of neurodevelopmental and neurodegenerative processes and it will be interesting to how these results might be influenced by therapeutic interventions in future studies. The researchers in a recent case-control study in Spain (n=690) concluded from their analysis that variations in the Amyloid Precursor Protein gene did not contribute to risk of Late Onset Alzheimer’s Disease (LOAD) in their sample group although effect sizes can be small. A Spanish group write about their experience of a 3-year longitudinal study of Mild Cognitive Impairment. Although there is a body of evidence relating amnestic MCI with conversion to Alzheimer’s Disease in their study, the researchers found this was more likely to be associated with multi-domain MCI. An American group have published research in which they identify a syndrome which precedes MCI and which they refer to as Pre-MCI. For those with Pre-MCI 28% converted to MCI or dementia at 3-year follow-up whereas only 5% converted in the Non-Cognitive Impaired group. The researchers identified Pre-MCI as

‘At baseline, Pre-MCI subjects showed impairment on tests of executive function and language, higher apathy scores, and lower left hippocampal volumes (HPCV) in comparison to NCI subjects‘

The researchers in a small German neuroimaging study (n=31) provided evidence of a relationship between connectivity in frontal-parietal networks and attention (assessed using the Attentional Network Task)  in people with early Alzheimer’s Disease. A moderately sized study (n=239) in a sample of people over the age of 85 showed a significant inverse correlation between intracranial volume, which the researchers used as a proxy marker of premorbid brain volume and risk of Dementia and more specifically Alzheimer’s Disease and Vascular Dementia. Interestingly in the group with the largest intracranial volume, dementia risk was not associated with white matter lesions. There is a write-up of the 2010 Leon Thal Symposium which covered amongst other subjects the establishment of a registry as well as approaches to data gathering. An American group have estimated the incidence of dementia and cognitive impairment not-dementia in the USA and over a 6 year period they estimate that there are 1.4 times as many incident cases of dementia cognitive impairment not-dementia as cases of dementia cognitive impairment not-dementia. NICE have just published their revised Technology Appraisal for drugs for Alzheimer’s Disease here.

Miscellaneous

There is a write-up of one study which provides preliminary evidence of a benefit from Transcranial Magnetic Stimulation in post-stroke dysphagia. This was a small trial and it will be interesting to see the results of further studies in this area. One cross-sectional study provided evidence of a positive correlation between hippocampal volume and recovery from PTSD in war veterans although replication of these findings with a longitudinal design is needed.

Index: An index of the site can be found here. The page contains links to all of the articles in the blog in chronological order. Twitter: You can follow ‘The Amazing World of Psychiatry’ Twitter by clicking on this link. Podcast: 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). It is available for a limited period. TAWOP Channel: You can follow the TAWOP Channel on YouTube by clicking on this link. Responses: If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk. 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: The Structure of Scientific Revolutions – Chapter 2: The Route to Normal Science.

In this chapter or essay as he refers to it, Kuhn writes about what he considers to be the route to normal science. In this chapter he elaborates on his distinction between normal and revolutionary science and it makes for interesting reading. Early in the chapter Kuhn suggests that textbooks offer scientists a medium through which they can arrive at a consensus. He also notes that the road to a research consensus is ‘extraordinarily arduous’. The textbook states the common problems facing a research community. There were two features he suggests are necessary for revolutionary science

1. Unprecedented findings which were sufficient to draw people away from other areas of study suggesting that there was a competitive element to the process.

2. That revolutionary science would be sufficiently open-ended to enable others to develop theories from this. In other words they could become ‘stakeholders’ in the process.

I applied the ‘Darwin test’ on this. What I mean by this is that Darwin’s theory of natural selection is so robust that for any philosophy of science should make predictions which can be tested and would hold true when applied to Darwin’s theory of natural selection. For the points above, I hope the reader will agree that Darwin’s work ‘On the Origin of Species’ was both unprecedented, produced a very strong following and also gave rise to an entire field of study which has been occupying scientists for the past 150 years.

Kuhn then goes on to discuss revolutionary science in physical optics and with regards to electrical phenomenon. In both cases he provides the reader with evidence that prior to the ‘revolution’ there were many small areas of research founded on different assumptions or attempting to explain different phenomenon. What comes after the ‘revolution’ in Kuhn’s interpretation is very interesting and I thought was very authentic. Thus he suggests that a language arises which can be readily understood by those outside of the research community although this changes very rapidly. After a time the community develop a specialised language. Those who ignore the revolutionary paradigm are ‘bred out of the profession’. The research community develops more specialised equipment to investigate every more specialised questions.

He also has some interesting things to say about different branches of science. Thus for the social sciences he suggests that the revolutionary paradigm may be occuring today (although this would have been some time ago when the book was originally written). However such a grand statement should be qualified with more specific examples to support his argument. Another possibility is that the social sciences may operate differently to the natural sciences in terms of how research communities are organised, behaviours within the communities and even the nature of the questions that are being posed. I would argue therefore that a much closer examination needs to be made in order to justify even simple statements of this type. The strength of his book lies in how he guides the reader from examples through to his conclusions and there is no reason why this should be abandoned when discussing a very complex branch of science. When he refers to medicine however he makes an interesting observation that this is strongly driven by an external social need. He also suggests that in astronomy the first paradigms arose in ‘prehistory’ and no doubt he implies that navigation by the stars was a necessary skill for hunter-gatherers. He also notes that technology assists in gathering data necessary for the development of a science.

For me Kuhn’s framing of the paradigm has another implication. My interpretation of Kuhn’s paradigm is that it is a function of the ‘minds’ of the scientists rather than a function of the underlying properties of the universe. In other words revolutionary thinking isnt so much about a better understanding of the world but rather one that is more successful in engaging the scientific community.

References

Thomas Kuhn. The Structure of Scientific Revolutions. Narrated by Dennis Holland. (Paperback originally published in 1962). Audible. 2009.

Appendix

For a review of Chapter 1 see here.

Index: An index of the site can be found here. The page contains links to all of the articles in the blog in chronological order. Twitter: You can follow ‘The Amazing World of Psychiatry’ Twitter by clicking on this link. Podcast: 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). It is available for a limited period. TAWOP Channel: You can follow the TAWOP Channel on YouTube by clicking on this link. Responses: If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk. 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: March 2011 3rd Edition

In the Neurocognitive Outcomes of Depression in the Elderly study, researchers have published findings which show a correlation between reduced stressors and subsequent improvement in cognitive scores (n=213). Decreased social interaction was a predictor of cognitive decline and although this could have been due to confounders, the relationship still held after controlling for variables such as depression status. One of the most interesting questions about antidepressants is why they characteristically take many weeks to reach a full beneficial effect. There are a number of studies which suggest that the antidepressants act to increase the number of synapses between neurons in the hippocampus – a region of the brain involved in memory formation. A recent murine study provides evidence that a class of antidepressants – the SSRI’s act in the hippocampus to cause one class of cells known as the granule cells to revert to a more ‘immature’ form which are able to form new synapses more readily.

A Dutch group has assessed psychosocial intervention for Alzheimer’s Disease guidelines across 12 European countries using a standardised protocol. Amongst their findings the researchers concluded that

‘The UK NICE SCIE guideline had the best methodological quality and included the most recommendations for psychosocial interventions‘

and that across Europe special attention is needed in terms of updating guidelines with evidence and implementing these guidelines in service delivery. In a longitudinal study involving subjects with non-amnestic and amnestic mild cognitive impairment (naMCI and aMCI respectively) (n=106) amongst other results researchers found that there was a decline in simple attention in both groups but a decline in divided attention in the aMCI group. The researchers suggest further research to corroborate these findings. Psychological constructs influencing verbal fluency were examined in one study which compared young and older adult healthy controls with people with Alzheimer’s or Parkinson’s Disease. Amongst the researcher’s results they found that processing speed was the strongest correlate of verbal fluency performance and they conclude that

‘the primary role of processing speed in performance suggests that the use of fluency tasks as measures of EF or verbal ability warrants reexamination‘

In an interesting study, researchers used post-mortem and structural MRI data to assess the volume of the hypothalamus in people with Frontotemporal Dementia. They found that the volume of the posterior hypothalamus was significantly reduced in those with behavioural variant Frontotemporal Dementia

Evolutionary Psychiatry

There is an open-access article on primate evolution at PLOS Genetics. An international group of researchers have looked at variation in 54 genes in primates in order to produce a more accurate phylogenetic tree.

Phylogenetic Tree from (Perelman P, Johnson WE, Roos C, Seuánez HN, Horvath JE, et al. (2011) A Molecular Phylogeny of Living Primates. PLoS Genet 7(3): e1001342. doi:10.1371/journal.pgen.1001342)

The diversion of human and Chimpanzee lineages is estimated to be between 6 and 7 million years ago from this analysis. There analysis sheds light on some of the earlier and more controversial diversions particularly regarding the New World Primates.

There is also an interesting open-access paper on Neanderthals and fire use in the Proceedings of the National Academy of Sciences here. The researchers looked at a number of sites used by archaic hominids in Europe and found no evidence of fire use by predecessors to the Neanderthals (e.g Homo Heidelbergensis) but repeated fire use by Neanderthals across sites. Although there is evidence of fire use by Homo Erectus at Koobi Fora (estimated at 1.4 million years before present) the evidence here suggests that Neanderthals were consistently using fire and this raises questions about how this consistency was achieved. For instance this may have been achieved through language. A current controversy in the literature centres around whether hominid brain size increased as a result of cooking or preceded this and so this has other implications. Contextualising these findings it’s also interesting to ask if early humans (Homo Sapiens) in Europe learnt their fire making skills from Neanderthals in order to survive in this Ice Age environment.

Index: An index of the site can be found here. The page contains links to all of the articles in the blog in chronological order. Twitter: You can follow ‘The Amazing World of Psychiatry’ Twitter by clicking on this link. Podcast: 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). It is available for a limited period. TAWOP Channel: You can follow the TAWOP Channel on YouTube by clicking on this link. Responses: If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk. 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.

Do Only Humans Smile?

Apparently smiling at a Chimpanzee is a mistake. Chimpanzees are thought to interpret this as a sign of aggression. Since Chimpanzees are our nearest living relatives this means that smiling (in the sense that this is a friendly sign) might be a distinctly human characteristic. While in Tamil Nadu, I was fortunate enough to have witnessed several instances of Bonnet Macaques baring their teeth at each other or while alone. Bonnet Macaques are Old World Monkeys and their ancestors are thought to have diverged from our lineage some 25 million years ago. The main clip below lasts some 2 minutes and includes several incidents of teeth baring obviously associated with aggressive confrontation between an alpha male and those jockeying for higher positions within the troupe.

There are a few interesting points to observe. Thus in the photogaph below we can see that the alpha male is baring his teeth and the other macaque is observing in a state of readiness.

This same macaque then slowly lowers into what I interpret as a position of submission. Thus in this instance the baring of teeth (supported with vocalisations) is associated with a submission response in the other macaque without resorting to physical conflict (albeit for a brief period). What is also interesting although difficult to be certain about is that the macaque combines the teeth baring with a downward movement of his eyes at one point.

The Macaque’s eyes quickly return to the upward position and this is somewhat reminiscent of human behaviour when one person might ‘look down their nose’ at the other person to signal that the other person has less perceived social value. In the case of the Macaques there is a clear struggle for social position. However the sceptic would be right to suggest that the above inference may be erroneous based as it is on a single observation. I had not stayed long enough to observe a repetition of this behaviour in the same context.

In the next clip, there is an even more interesting occurrence. This time a Macaque can be observed sitting on a tree baring its teeth. While this may also be an isolated occurrence, the first association that came to mind was that of an actor rehearsing their facial expressions in front of a mirror.

Perhaps the Macaque was recalling an earlier confrontation and re-enacting the scene or else preparing for a future confrontation. In the first clip the reader might agree that there is an element of ‘performance’ to these confrontations and that the analogy with actors may hold scope for future exploration.

So what does all of this tell us?

Firstly a macaque can bare its teeth to reduce the need for physical conflict. This might result from classical conditioning. If a Macaque lower in the hierarchy has lost several encounters with the Alpha male and these conflicts have been associated with biting, then baring of the teeth becomes associated with ‘punishment’ and the submission response may follow. This may be avoided if the context is different. In other words if such conditioning does occur then the Macaque might be able to over-ride this when it cooperates with another Macaque to attack the alpha-male.

Secondly although humans show their teeth when smiling this particular behaviour of baring teeth in the Macaques is associated with hostility and confrontation. Thus the emotional correlates appear to be quite distinct.

Thirdly there is possible observational learning in the Macaques. Towards the end of the clip, the Alpha male bares its teeth at two other Macaques and is quickly joined by an ‘ally’ who follows this behaviour. Perhaps these facial expressions can be used to forge alliances.

So the last question is why do people smile as a friendly signal instead of as a sign of hostility? I’m sure the reader might have some good ideas about this. My thought is that Chimpanzees and Macaques use their teeth when fighting each other whereas this is not typical in humans. So the teeth have lost their association with hostility and become more associated with activities such as laughing and sharing food. People such as Professor Robin Dunbar have suggested that laughing in humans has taken the place of grooming and so the association of smiling with laughter would reasonably make it a more friendly activity.

Perhaps a close examination of Bonobos (a close relative of the Chimpanzee who have interesting social traits) might give us some insights into how people gained their smiles.

Index: An index of the site can be found here. The page contains links to all of the articles in the blog in chronological order. Twitter: You can follow ‘The Amazing World of Psychiatry’ Twitter by clicking on this link. Podcast: 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). It is available for a limited period. TAWOP Channel: You can follow the TAWOP Channel on YouTube by clicking on this link. Responses: If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk. 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.

Blogging About Law and Depression

There’s an interest blog  about depression – ‘Lawyers with Depression‘. Although there’s no About page, the articles are posted by Daniel Lukasic – a lawyer who writes and talks about depression and whose work can be found at other sites also. The blog uses the wordpress platform and begins in May 2009. The articles are dated, titled, comment enabled and identify the author of the post. The text is complemented with photographs. The articles can be navigated either by clicking on the next/previous entries link at the bottom of the page or else through the use of a boxed chronological drop-down index on the right-hand side of the page. There is a blog roll on the right side of the page.

Lukasic’s posts tend to be several paragraphs in length and he is able to talk about his own experiences often sharing his own coping mechanisms and insights with readers. In this post, Lukasic writes a little about his own personal experience with depression and focuses on the strong link between stressors, anxiety and depression with a few useful references for the interested reader. In various posts, Lukasic writes about important topics such as the benefits of gratitude, managing anger, and the importance of communities.. In this post, Lukasic talks about the use of time contrasting between the use of time as a ‘commodity’ and spending time ‘living’. Similar themes are developed through the blog and here Lukasic writes a searching article about the ‘Rat Race’ and he suggests that successful completion of a journey is rewarded rather than enjoying the experience of that journey. In this post, Lukasic writes briefly about having the right chemistry with a therapist during treatment. There’s a well-resourced post on Seasonal Affective Disorder here. In these posts, Lukasic writes a moving account of depression in the legal profession (although this is a theme throughout the blog as the title suggests) including depression in law students and judges and the difficulties they experience.

Lukasic offers a well-rounded perspective on depression in the legal profession, offers readers useful resources, brings his own personal experience into the subject and highlights a problem that is being increasingly clarified and addressed. Lukasic writes courageously and in so doing offers a voice for others in a similar position who have experienced depression.

Index: An index of the site can be found here. The page contains links to all of the articles in the blog in chronological order. Twitter: You can follow ‘The Amazing World of Psychiatry’ Twitter by clicking on this link. Podcast: 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). It is available for a limited period. TAWOP Channel: You can follow the TAWOP Channel on YouTube by clicking on this link. Responses: If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk. 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.