11390296 Heyes

Interesting article about l IFC and its role in imitation.

Quite a multidisplinary artilce.

Most relevant info I needed were in Box 3.

Activation in relation to observation of MEANINGUL action (regardless of intent of the observer, to imitate or not). Recognition theory is probably more useful. of MEANINGFUL actions (with a purpose).

PMC1569489 M. Petrides

This is one tough cookies to crack! Holly smoke! Took me good three days of reading and still not sure how much I understood.

Key points I need to recall:

  • Region 10 frontal pole regions might be the ultimate highest level of abstract thinking
  • DLPFC under control of region 10
    • heavily involved with MONITORING
    • Defined as not just remember/familarity but have to process the memory somewhat
  • IFC under control of region 10
    • making a decision/judgement
    • BUT also can process interact with working memory

Key Figure 4, 8, 9

The PET image is quite convincing but I wonder why it is only on the right side.

15937012 M Petrides

The only reason I’m reading this one is to understand what’s is the purpose function deficit lesion related to lateral prefrontal cortex and how everything could potentially be tied together and what specifically the spring region would be responsible once we observe interesting alterations.

Factoids:

  • Can’t believe Brodmann’s map has been more than 100 years old at this point… and we still have and produce anything “better”?

 

23440466 Alex’s Delayed Discounting

I still remember the day when my supervisor was reviewing Alex’s manuscript and how angry he was and that he meant Lee disagreeing with Alex’s premises during OHBM2012 back then. Can’t believe it’s been have a decade already.

I was still quite green back then and the in many ways I wasn’t even sure half of my supervisor’s argument against Alex. Fast track almost half a decade later I’m pretty sure my supervisor has reached a mutual appreciation and admiration with Alex work.

So guessing in a way I am saying is it’s quite emotional for me to review this paper and his review of this entire field about delay discounting which looking back in consideration with all the aforementioned value attribution deficit that has been reported, it makes a lot of sense.

I feel the many ways procrastination is self being the way it is a signal of value attribution deficits.

in a way you can see this social defeat and hopelessness as a problem and of value attribution where they discount the future so much that they do not believe it has any values by over projecting and playing so much emphasis on the current state of things

Alex laid out some very convincing perspective about the ventromedial PFC and its involvement with expected value attribution.

Ashley really enjoyed that because Alex put everything especially with regard to his prominent past few experiment in delay discounting into a rather simple and easy to approach language much easier to digest than the original manuscript if I recall correctly. I like how he tied a ventromedial PFC and its relation to value attribution together’s backed by multiple meta-analysis (which is… what really good discussions should be all about).

I’m not fully convinced of the last bit about Pavlovian conditioned response to social disharmony but is raise a very interesting perspective about the importance of evaluating social decision-making which is sorely lacking in most conditioned laboratory examination and study of suicidal behaviour. I might be just too sceptical on that although I look forward to his more prevail and work in that field. I do know a few suicide researchers who have already begun conducting Ultimatum task in a variety of healthy population unit to better understand decision-making. However any kind of imaging or advanced acquisition modality on suicidal or even parasuicidal populations are such a PITA to study, Even when attached to a full clinic.

Iowa gambling task Cambridge decision-making task and probability reversal task are quite insightful.

Reference check:

  • Expected Value: 59
  • learned value: 60
  • VMPFC: 61

21385016 Jollant’s Review in World Psychiatry

I guess that this is one of the most difficult articles for me to review because for me it is very hard to remain objective.

It certainly has been a while since I first read this article. In the beginning I was very very sceptical as usual. Looking back I a and agreed that the scepticism is somewhat misplaced after reading extensively in the broader per referral field that helped converge on the conclusion that was drawn by Dr. Jollant.

Overall, I agree the single strongest point of this article above or under is its proposition to propose and come up with a model that further refined earlier proposition with regard to the brain and its relation to various neural cognitive process behind the pure theoretical  cognitive model of suicidal behaviour. Previous reports focus heavily on the behaviour aspect without really brandishing any neurocognitive data that could substantially or remotely validate the theory and proposition of the models. See earlier article.

Dr. Jollant proposed three stage model that are related to the value attribution,emotional modulation, and facilitation of act. Despite the fact that I don’t think these three values would neatly be correlated with ventrolateral prefrontal cortex/OFC, MPFC/DMPFC, and DLPFC, I think it is certainly a great direction to take with regard to upcoming and impending recognition of brain circuitry instead of regional specialization which contributed to the symptoms.

The fact that ventrolateral free of prefrontal cortex and OFC are so prominently featured in many reports across a great variety of article suggests that it may be the focal point or a critical node that may be at the interception of all three processes instead and hence of key vulnerable point among all potential interruptions.  After all, brain is plastic and any disruption within the circuitry would not necessarily guarantee the interruption of the entire function of the circuitry. However and critical nodes when it is responsible for multi-role converging on the same sets of vulnerability that contribute to the suicidal risk main results in that particular region being far more provincial and among all  structural or functional alterations.

In many ways I feel the current literature of trying to come up with his sets of brain region and understanding its specific role may be flawed. Instead what we could be looking for are the interception points toward a critical nodes where value attribution emotional regulation and inhibition functions converge. Hence the interruption of these regions would greatly increase the risk asked implicates multiple cognitive process that simultaneously and synergistically contribute to the suicidal behaviour.

I’m a firm believer that brain regions specialization at a higher cognitive level is a relative myth. Just as similar as to how memory cannot be pinpointed to a specific regions, the transient networks within the brain may be responsible for our lot of the higher cognitive process that we take for granted, unlike the lower sensory or motor processes.

I think the issue is that I’ve been to fixated on finding the precise function of each regions and trying to pin them down like what Dr. Jollant did earlier. Maybe if we take a step back and look at everything as a probability event where déficits or alterations can happen anywhere within the circuitry and the mere statistical convergence of these events are the ultimate findings we conduct and comparisons. From that perspective, and adopting a vulnerability perspective where suicide is the combination of a variety of vulnerabilities such as decision-making value attribution cognitive inhibition and emotional regulation then findings of each experiment can indeed be vastly different  because we are comparing deficits across multiple circuitry’s which could break anywhere that resulted in the culmination of all of the circuits being compromised. Our spatial findings using neuroimaging approach may merely shed light on the spatial convergence of the circuits that with the same amount hits (borrowing a lingo from cancer genetics here), the most vulnerable spots that could result in a phenotypic appearance of suicidal behaviour. it’s time like this that I wish I had known more about multiple hits hypothesis and the lesion studies of suicide.

(added two studies to be reviewed)

  • There are certainly a lot of negative emotions that I would activate the lateral orbitofrontal cortex.

 

A good analogy I can think of about what exactly brain imaging is doing it’s like a measuring the heat of an engine while trying to understand where the car went.

 

 

 

24632395: Zhang et al from Qiyong Gong’s suicide research group

Before I go too far just like to say that it has been my suggestion to my PI to collaborate with Qiyong Gong’s group in fact around early 2012 after OHBM in China went to specifically meet with him just to make an introduction. Dr. Gong  subsequently made a few interesting presentation at ISMRM2015 and either one of the SOBP or ISAR meetings.  My supervisor never took it seriously and for fear of lacking support and never really followed further because I just assumed a naïve young so set a researcher will not make an impact by myself when PI doesn’t want to follow through with a more extensive collaborations.

In hindsight that it was a big mistake, Dr. Gong’s  research group, at least according to my contact in China, was quite proficient who is medical imaging and while he has revolving emphasis on psychiatry and applying neural imaging their group has been incredibly productive while my PI closed shop. Fun time indeed.  Too bad I am leaving this field pretty soon otherwise it would have been a very interesting collaboration.

From the around the time when my supervisor finish his review of the   suicide neural imaging works,  quite a few reviews came out around exactly the same time….

vanHeeringan, 2011/2014; Zhang 2014, Jollant 2011; Desmyter, 2011.. Just to name a few.

over the short span of about four years about almost 5 identical review has been published and not including the book chapter that I contributed which is nowhere to be seen. Not even sure if that made it into a book yet but  I really do not care that much at this point. lol.  anyway that just about is that we have way more summary that merely catalogue and summarize the findings without providing use for interpretation into the details of what exactly this finding could mean from a neutral anatomical region by region breakdown and more importantly the interconnection among them. Partly it is because diverse analytical approach but partly also because there is no objective and quantitative way to really combine these findings in a consistent manner to produce a potential framework contribution of each individual regions.  just like I have mentioned so far, many of these articles and reviews emphasize these regions but still to this date we do not know what the precise impact of this region would meet. We have lunch that he could be involved with decision-making, it is inhibition, with its emotional control but how certain our wheeled them? Do you really want to put a P value on how certain we are?

while I am firmly believed joy in my PhD defence I was glossing over and potentially ignoring some of the more physiological findings such as the serotonin system such as the glucose metabolism and the cerebral blood flow analysis I absolutely believe those are important and help contribute and potentially explained the alteration within the orbital frontal cortex region but we can have only hypothesize that these reduced blood flow reduced glucose consumption leads to potentially grey matter volume reduction which potentially showcase functional implication such as decision-making emotional regulation inhibition deficits however the correlation does not imply causation as many many many people have reiterated this points this type of hypothesis needs to be validated using TMS or effective connectivity study to really drive this point home we have many pieces that formed this puzzle from the pet suspect fMRI regular structural MRI but we do not know to causation and what what what we are observing whether is the effect or source of the problem.

This is also the reason why I am reviewing all of these reviews of neural imaging studies, by going through them systematically I hope I will start to see a commonality and trend that typically not rendered anywhere else.

Such as what I am building in Xmind.

Anyway onto this article.

  • He mentioned several interesting possibility about various subtypes of suicidal behaviours and how different morbidity would differ from each other which would partially fit into my theory and prospective thoughts impulsivity related to suicide are vastly different from elderly suicide and may further explain the lack of consistent heterogeneity which in suicidal behaviour itself.
  • Brought up the prefrontal amygdala connection again here.
  • Brought a good emphasis on Leyton’s paper on tryptophan trapping that has been reduced in the OFC and the ventromedial prefrontal cortex.
  • Also mentioned a very good point about Benedetti’s discussion in 2011 which mention how OFC can be potentially tied to cognitive rigidity
  • mention a good point about stratum and how that’s associated with impulsivity is primarily measured and delayed task
  • Like this paper’s anatomical driven approach to data analyses. I think part of this paper inspired how I would normally organize my thesis around anatomical region trying to conciliate all these findings together.
  • Brought a good point about cell morphology changes in the anterior cingulate cortex.
  •  This paper brings out a lot of emphasis on Putman and its role in cognitive control and value attribution per Alex Dumbrovski’s paper.
  • Jia’s WM tractography paper is one of the multi-model confirmation in addition to the tryptophan trapping analysis that emphasizes the alteration and orbitofrontal cortex region.

 

Overall I think it’s a very interesting paper review that offers more innovative thinking and integration of the putamen and thalamus which have been previously underappreciated however the fact that dorsolateral prefrontal cortex has not been extensively incorporated in this is a major cause of concern and may not gyre well with existing Meta-Analysis looking at inhibition regulation issues. Overall has a heavy emphasis on orbitofrontal cortex and anterior cingulate cortex and their contribution to cognitive control and emotion regulation while attribute far less to dorsolateral prefrontal cortex.  I think I have unconsciously  incorporated elements of the stratum and thalamus findings into my thesis but I would say the biggest lesson I remember from this paper it is still up output in minutes renewed emphasis on elevated impulsivity ass evaluated through delay discounting

 

 

 

 

Neurobiological risk factors for suicide insights from brain imaging

American Journal of preventative medicine

Elizabeth T Cox

I honestly never heard of this group over my brief almost decade of participating in neuroscience research  of suicidal behaviour.  However,  looking forward to see what I have to say in this brief paper.

  •  research was conducted on March 2 some supporting
  •  structural diffusion suspect had functional

structural alteration

  •  grey matter volume reduction
    • orbitofrontal cortex is heavily implicated in MDD BD schizophrenia and BPD
  •  grey matter  volume increase
    •  amygdala MDD and schizophrenia
  •  I forget where I read this but I think it was in the suicide model wears a mention to vulnerability up much more likely to trade like deficits whereas there is far less sinks from the genetic study that mentioned far less heritability of suicidal ideation suggesting the vulnerabilities more responsible to facilitate the transition from suicidal ideation to suicide attempt
  •  to mention a good point about elderly sued the side show consistency with younger suicide
  •  I like how this paper breaks down so set attempt terms of their age range
  • they also mention a good point about the lack of longitudinal studies
  • overall it highlights the same elements existing data’s conversion and orbitofrontal cortex of the tutus on the 14 but sceptics in me keep questioning if that is the results of people trying to attempt to replicate earlier study and increasing whatever threshold to find them is truly novel independent objective replication of the findings
  • being in the publication fields I am strongly suspicious of number two but on the other hand I also have to give credits that the chance of all researchers affected by it is relatively small
  • I really wish these authors made the study data public such that they can stand to the scrutiny of time
  • overall this paper highlight the importance between amygdala and orbitofrontal connections
  • however still lack a consistent and plausible theory of interpretation of these alterations
  • I do like the fact that they mentioned numerous functional findings and how that heavily emphasize and reinforce the OSC alterations from the metabolic perspective

 

 

Neuroimaging Meta-analyses of Suicidal Behaviour.

Imaging analysis Suzette behaviorist not being a  strength.

multiple methodology disturbances and inconsistencies and definitions have resulted in a much difficult summation of findings.

Heeringen’s  The paper in 2014 was one  of the   cornerstone of  neuroimaging research.

  • suicide attempt is involved 40% of also set cases
  •  stress – vulnerability all
  • Texas is a models into many models. As this model is one of the most common one that is we are trying to undermine explain away so I do not sufficiently have it using it to gauge for what it does exist as an individual
  • do you live on the basement analysis of structural and functional imaging studies coordinate based meta-analysis you want to
  • ginger ALE analysis
  • Actually a lot of the study has been extended for one reason or the next
  •  coordinate based meta-analysis of neuroimaging results
  •  reporter foci would interpret us centre for 3-D   Gaussian probability distribution
  •  uncertainty is interpreted as a function of between template and between  variance
    • between subject variances further  exacerbate by individual sampl
  •  commonly observed structural alterations
    • 3 important.
    • caudate nucleus: -16.75, 13.77, 8.46
    • superior temporal gyrus: -41.49, -31.9, 8.14
    • rectal gyrus: -9.93, 35.81, -19.08
    • majority of these are related to negative emotional processing
    •  these are structural alterations and may be related to the punishing aspect of the events which subsequently affects the planning and mediation part of the behaviour
    • one possible interpretation of these areas they mediate how people react to negative events
    •  most likely involved with its ideation to sue site attention session
  •  commonly observed  functional neuroimaging alterations
    • right anterior cingulate: 14.4, 44.9, 7.28
    • posterior cingulate: 13.7, 11.2, 43.5
    •  rostral anterior cingulate cortex:  emotional context activate this region
      •  increase activation and current analysis
    •  dorsal interior singlet cortex are related to non-emotional stimuli
      •  decreased activation Iowa but gambling task
  •  limitation of  the study is set to only few studies included and all of them have to be whole brain correlated.
  •  is a strong inference in relation to Dr. July and patents functional study which means pejorative them are more likely to be involved in decision-making deficits
  •  results are not readily applicable to elderly suicides
    •  a set is one of the exclusion criteria
  •  we also assume that what whatever we observe a separate presentation of vulnerability and not a state change
  •  ginger ale bypass some of these problems which we ignore such as acquisition parameter statistical thresholds was an carnal registration abnormality stander space used by using a caution distribution of uncertainty to summarize these variations

 

TLDR:

  •  discussion mentions several interesting connections of destructible and functional implication between these altered regions and how they could be tie into serotonin and especially through the stratum alterations
  •  overall no one really knows what is going on but you are making effort to attempt to guess what exactly we are seen
  •  caudate OSC and ACC artistry mentioned that he heavily emphasized in this paper along with the superior temporal gyrus.
  •  I had a lot higher expectation of this paper in the hope that this will be finally the meta-analysis papers or summarize everything but so far it only summarize a very small subset of all the studies.
  • The Tanaka 2004/2007 papers are very interesting to read  acid could potentially draw the implication of serotonin integration and also stratum area alterations.
  •  also mentioned several interesting study to try to type in the structural and functional alterations which are always some weakness to interpret
    • De Kwaasteniet 2013 is cool
    • Wagner 2008
    • Scheuerecker 2010
  • Lindquist  2012 for the functional architecture of the brain.

Impulsivity and where it fits in

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1925038/

  • impulsive distention impulsive control disorders typically have a much earlier onset around 7 to 15!… teenage years.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3638385/

  •  there are many different aspects of impulsivity and they can be measured using a variety of different types of tasks this paper goes into little more details about the different types and some construct of impulsivity and what they have shown to be altered

 

Brend and Mann 2005

Adoptions Studies:

  • Schulsinger 1979:
    • biological relative of adoptees who died by suicide
    • adoptive relative of adoptees who died by suicide
    • control adoptees
    • 6x higher potentially
  • Wender 1986:
    • 15x mood disorder adoptees
    • “affective reaction:”impulsive/unstable/cluster B personality
      • impulsive aggression: liability to respond with hostility or aggression to provocation or frustration
      • (even higher than mood disorder)
    • Suggest that different types of suicide have a variety of heritability???
      • So even though the commonly cited 20% commonly though present suicidal heritability of suicide across all, in certain cases the heritability might be higher and mo

Twin Studies

  • Roy and Segal 2001: Higher concordance rate for suicide and suicidal behaviour:14.9% vs 0.7%, 23% vs 0.7%
  • Roy et al 1995: concordance rate of suicide attempt 38% vs 0% in the surviving monozygotic twin.
  •  is not attributed to the treatment reactions risk of suicide. Nonsuicidal diocese similar

Twin registry:

  • Statham, et al 1998.
    • 6k monozygotic versus heterozygote’s registry across Australian twins
    •   approximately 40 to 55% from  ideation to attempt
  • Glowinski, et al. 2001.
    • 3.5k Missouri  the female adolescent twins
    •  concordant suicide attempt 25% in monozygotic 12.8% in dizygotic
    •  unadjusted rates tenfold,  adjusted rates fivefold
    •  48% heritability for suicide attempt
  • Fu et al. 2002
    • 3.3K  to be a nun interrupting the registry
    • unadjusted heritability is between 30% to 43%
    •  adjusted  ideation is 36% and attempt around 17.4%
    •  shared environmental variable explain about 20% of suicide attempt but not of suicide ideation

One interpretation is what subject to genetic component is more related to attempt, which is the conversion from ideation to attempt and the actual trigger of ideation is more  immediate stressor.The facilitation of the transition from ideation to attempt is more likely a biological component which is what was proposed by John Mann’s model ( predominant disinhibition).  overall it is a lot harder for biological mechanism to program a specific time to cause ideation than it is to cause transition from ideation to attempt.

However on the flip side of that, why cannot biological components be accountable for the suicidal ideation instead, albeit  untimed?  assembles should be also possible because certain cognitive deficit would could potentially render the patient’s more susceptible to environmental emotional influence hence more likely to trigger suicidal ideation.  good luck testing that though.

Family studies

  • were similar
  • suggest clinical phenotype of suicidal behaviour transmitted is both suicide attempt as well as completion
  • these typically involves accounting for the mobility heritability
  •  cannot distinguish between
    • unique diathesis
    • genetically transmitted new and distinct form psychiatric disorder
    • particular severe form of disorder
    • comorbidity condition
    • imitation
    • shared genetic environmental effect
  • Familial suicide
    • 3 to 4 fold elevation
    • Tsung, et al. 1983: 8% in suicide patients 2% in  no suicidal patients and 0.3% in controls
      •  to suggest that comorbidity elevates the risk of suicide which are heritable but there are also independent separate contributing risk to suicidal behaviour as well
    • Egeland and Sussex 1985:
      •  76% suicide in 16% of sample families
      • pedigree suggests a familiar loading of mood disorder as well as suicide
      •  interesting fact is we still do not know if it is additive risk or multiplicative or if this is the guarantees dioceses or more severe form of mood disorder or a very commonly shared environmental effect
      •  but we  definitely see it, and occurring a lot together at the same time
    • Powell 2000:
      • family history 4.6OR
    • Foster 1999
      •  current psychopathology implemented in the strongest risk of suicide completion
      • 3?
    • Tsai, 2002
      • 15.1OR
  • Population registry:
    • Qin 2002: Family history of AOR 2.58
    • Agerbo 2002: Paternal 2.3, Maternal 4.8
    • Qin 2003: 2.14
    • Runeson and Asberg 2003: OR: 1.98

Familial Suicide Attempt from Suicide Proband.

  • Gould 1996: 5.1
  • Brent 1996:
    • one of the key inside that was highlighted within this article is about aggressive versus nonaggressive completers and their differences in terms of familial aggregation of suicidal behaviour
    • 15.6% versus 2.9%
  • Cheng 2000:
    • OR: 5.2

Familial Suicidal Attempt from suicide attempt proband

  • Roy 1983: OR 3.4, high risk in early parental  demise
  • Mitterauer, 1990: OR 3.3
  • Linkowski, 1985: OR 2.0, 3.5 violent attempt
  • Sorenson, 1991: OR 5.8
  • Malone 1995: OR 7.6

High Risk and Longitudinal Studies

  • The peak of incidents for new onset of attempters are between 15 and 30 years old.

Thoughts. Blobs. Ideas and Headaches.

  • After reading this review paper I think the number I would that on in terms of familial risk of suicide is about OR of 3 across various studies after accounting for various comorbidities, 5 for attempt. 0 to 1 for ideations.
  • This is interesting. It is self because suicide attempt is not guaranteed to be successful as it depends on various other factors determined by the environment and circumstances.
  • This could bring for the emphasis to medial prefrontal cortex and dorsolateral prefrontal cortex into focus because decision-making and cognitive inhibition are key cognitive deficits  regard to the transition from ideation to the actual physical act of attempting suicide.
  • Familial odds ratio of attempts might actually be higher
  • We still do not know the interaction if it is  independent or interactive with the risk posed by comorbidity and this supposed suicide suicidal diathesis.
  • I gotta say this article is one of the better structured article that I was able to follow quite easily from one paragraph to the next with a clear hierarchy and delineation of each studies which made reading quite a joy.
  • I used to think regardless of how an article is written that data should speak for themselves but I realize soon without a good organization and systematic orientation of the data, most people will not even bother to read the paper and will just fall asleep like me. Amen to lazy human nature.