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Cognitive Regime Shift II - When/why/how the Brain Breaks/SusanFitzpatrick

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Notes by user Susan Fitzpatrick (JSMF) for Cognitive Regime Shift II - When/why/how the Brain Breaks

Post-meeting Reflection

1+ paragraphs on any combination of the following:

  • Presentation highlights
  • Open questions that came up
  • How your perspective changed
  • Impact on your own work
  • e.g. the discussion on [A] that we are having reminds me of [B] conference/[C] initiative/[D] funding call-for-proposal/[E] research group

I VERY MUCH LIKE THE idea of taking one disorder -- say Parkinsons and see if we can 1) describe what is meant by Parkinsons at multiple levels of analysis 2) accumulate observations (genetic, circuit level, behavioral and environment-social) that contribute to individual variability - again at multiple levels - especially looking at those patients with more rapid or slower disease progression and 3) account for differences among cartoon models of the disease and the actual disease and 4) develop a dynamic understanding of disease progression and what deviations occur and why.

I am not sure why David K disparages the use of the term brain state -- as I could see that there are constellations of factors at multiple levels that lead to a "healthy" functioning state adaptable to the context. ANs this space could be quite large. One could then imagine vulnerabilities or insults that could push the brain in ways that result in a "state" change such that the brain is now dysfunctional in a life context or loses adaptability. And one can further imagine a brain getting itself trapped in a part of brain space where it is hard to see that any perturbation (treatment) or slow recover processes would allow for recovery. It is probably not a coincidence that the numbers of individuals with severe brain disorders are about what one would expect from being in the very tales of a distribution. The individuals who are 2-3 standard deviations out are those for whom treatments could work -- but what moves someone and what keeps them?

We need a framework that gives us some deep multi level understanding so that we can better access if tweaking X really does impact Z or is the tweak in X actually resulting in an adaptive response in Y that then impacts Z (or maybe stabilizes Z so it does not change or becomes resistant to the X perturbations).

In aging I believe we need a better understanding of what happens to adaptive dynamic systems over time ("as the age" or over life span) so we know whether the changes we see are nothing more than what we should expect and maybe it only seems maladaptive because the environment changes or what we now expect our systems to do at different ages has changed. How do we keep our brains adaptive and responsive -- to continue to explore rather than exploit. This is a different challenge than diseases.

Today I was very struck by our inability to work across levels or to even identify what level is meaningful for what we care about -- and what I care about is using neuroscience and complex systems to advance our understanding of and care for individuals with brain disorders - particularly disorders with no identifiable anatomical lesions. 25 years ago I initiated a program supporting neurorehab research on the premise that information learned about brain-function relationships should be useful in delineating what is and is not possible for recovery.

We have to understand the dual nature of individual differences 1) the many to one mapping -- there may be lots of ways for us to use of our brains to live adaptably in the world and yet - there seem to be a small number of stereotypical ways that brains break.

Mental health probably offers us the biggest challenges. If we could make a difference there -- even re-framing the way we currently think about these disorders - I think this would be a HUGE contribution.

Could it be that mesoscale dysfunctions -- depression, schizophrenia could benefit from mesoscale interventions -- perhaps all the lower levels changes we come to catalog will then come along for the ride,

For aging -- in pathology -- neurodegen -- treatments might require both a perturbation and a stabilization?

Reference material notes

Some examples:

  • Here is [A] database on [B] that I pull data from to do [C] analysis that might be of interest to this group (insert link).
  • Here is a free tool for calculating [ABC] (insert link)
  • This painting/sculpture/forms of artwork is emblematic to our discussion on [X]!
  • Schwartz et al. 2017 offers a review on [ABC] migration as relate to climatic factors (add the reference as well).

Borsboom et al. 2019 challenges the idea that reductionist approaches are appropriate for studying complex human neurological disorders and suggests that network approaches might offer alternative conceptualizations explaining dysfunction.  Do network approaches offer novel ways to both explain and intervene on “broken” brains?

Reference Materials

Title Author name Source name Year Citation count From Scopus. Refreshed every 5 days. Page views Related file
Brain disorders? Not really: Why network structures block reductionism in psychopathology research Denny Borsboom, Angélique O.J. Cramer, Annemarie Kalis Behavioral and Brain Sciences 2019 0 0 Download (Encrypted)
Searching for rewards like a child means less generalization and more directed exploration Eric Schulz, Charley M. Wu, Azzurra Ruggeri, Björn Meder bioRxiv 2018 0 11
The Effects of APOE and ABCA7 on Cognitive Function and Alzheimer’s Disease Risk in African Americans: A Focused Mini Review Chelsie N. Berg, Neha Sinha, Mark A. Gluck Front. Hum. Neurosci. 2019 0 0 Download (Encrypted)