29-31 May 2019, Charlottesville: UVA Brain Symposium

[Daniel-Mietchen]

as per https://braininstitute.virginia.edu/symposium

[Daniel-Mietchen]

I registered.

[Daniel-Mietchen]

Jim Ryan

• looked at legal definitions of learning disabilities, entitlements to special education and poverty-associated modulators like food insecurity, or exposure to toxins
• outlined a set of developments away from special education for some to personalized education for all

Kevin Pelphrey: Prediction of Treatment Response & Mechanisms of Change in ASD

• https://tools.wmflabs.org/scholia/author/Q61050146
• lack of biomarkers perpetuates the status quo in terms of inexact treatments, waste of time and resources
• Pelphrey et al. (2003; Journal of Neuroscience) on dedicated brain networks for tracking movements of fellow humans
• Bjornsdotter 2016, JAMA Psychiatry: social versus non-social motions; used machine learning
• NIH Autism Cener of Excellence, focusing on Girls, who are typically understudied in autism research
• Werling and Geschwind, 2013, Curr Opin Neurol

Michelle L. Olsen: Altered Astrocytes in Rett Syndrome

• https://tools.wmflabs.org/scholia/author/Q56582346
• breathing abnormalities
• central apnea
• ambulation
• MECP2
• inwardly rectifying potassium channel in astrocytes; Nwaobi et al., 2016
• hypercapnia
• gap junction

[Daniel-Mietchen]

Micah Mazurek: Autism Assessment: Challenges and New Directions

• definitions of autism has changed over time, as measured by criteria stated in DSM
• zooms in on changes from DSM-IV to DSM-5
• makes it hard to understand the scope/ inclusion/ exclusion criteria used in a particular study, unless the criteria are spelled out very explicitly
• thus, metastudies/ aggregations are harder, and so it is to deduce recommendations (clinical, behavioral, educational, legal etc.)

[Daniel-Mietchen]

Gerald D. Fischbach: Autism a Hopeful Time: What We Know and What is Next

• https://tools.wmflabs.org/scholia/author/Q5549123
• after learning disorders, muscular/ movement disorders are next in terms of frequency
• some animal studies instill hope in that they have demonstrated that symptoms can be reversed
  • example for Rett Syndrome-like symptoms in a mouse model: Guy et al. 2007 Science 315
• Purpura, Science 186,1974
• lists ethical conduct of research as an integral part of the scientific method
• refers to the paper "Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2" as an example, where first and last author are from Israel and Libanon and collaborated on research while their contries were at war

Huda's profile: https://tools.wmflabs.org/scholia/author/Q1633764

[Daniel-Mietchen]

Sonia Vallabh and Eric Minikel: A Path to Prevention of Genetic Prion Disease

• https://tools.wmflabs.org/scholia/author/Q64157038
• https://tools.wmflabs.org/scholia/author/Q64157069
• motivated by personal experience: mother of Sonia died of a prion disease (familial fatal insomnia) within months of symptom onset
• they did genetic testing; Sonia has inherited the corresponding mutation
• both gave up their original jobs and started a PhD program (at the Broad Institute), from which they are to graduate tomorrow
• now working on antisense oligonucleotides against the prion protein mRNA
• results promising, works fine in mice
• now onto clinical side
• found CSF-PrP as a biomarker
• they have something up on bioRxiv
• got FDA to support their request for Accelerated Approval of a clinical trial by claiming that they are as sure of the mechanism as there is certainty that AIDS is caused by HIV, for which Accelerated Approval was set up in the 1980s
• "genetically informed approach to drug development"
• some further resources
  • https://www.prionalliance.org
  • https://cjdfoundation.org/
  • http://www.cureffi.org/

[Daniel-Mietchen]

Christopher Barrett: Decentralized Cognition in Naturally Occurring and Engineered Intelligence

• decentralizing cognition by augmenting it with technical systems
• "extended minds"
• mentions Heider & Simmel paper from 1944, similar to the Braitenberg vehicles
  • "nothing of what you thought when you saw this is in there"
• described a dataset that they are analyzing that comprises activity patterns of most people on the planet (7 billion) at the scale of hours to minutes
• brought up another example: Chandana Paul XOR robot
• individual perceptrons cannot do XOR, bot combinations of them can
  • this means that logical relations like XOR can be created through networks, even if the individual components cannot produce that behavior by themselves

[Daniel-Mietchen]

William Petri: Neurodevelopment of Infants in the Urban Slums of Dhaka, Bangladesh

• https://tools.wmflabs.org/scholia/author/Q27663335
• looked at correlates of malnutrition, e.g. underweight, stunting
• correlated that with neuroimaging and metabolomics
• working in both slums of Bangladesh and in the US
• malnourrished children in Bangladesh seem to have higher brain connectivity than controls; differs from US
• significant technology transfer to Bangladesh, e.g. setting up a 3T MRI system in the hospital inside the slum

[Daniel-Mietchen]

W. Jeffrey Elias: Focusing on Neurologic Disease https://tools.wmflabs.org/scholia/author/Q50231739

• some early enthusiasm for ultrasound as a therapeutic technique in the late 50s and early 60s
• enthusiasm was severely damped by the fact that
• MRI-guided focused ultrasound
• ultrasound propagation is modeled based on the MRI, then actual ultrasound stimulation applied based on that simulation
• first application of transcranial MR-guided focused ultrasound was in 2009, for essential tremor
• later methodological advancements concentrated on increasing the number of ultrasound emitters inside the system; currently normal is 1024
• when in the scanner, intense testing through variation in location, frequency and intensity of the ultrasound, with MRI as a thermometer (ca. 1°C), then precise application of the actual therapeutic ultrasound
• early criticism "one step backward" because focused ultrasound is destroying tissue
• subsequent clinical trials focused a lot on quality control
• exploring further applications, beyond tremor: Parkinson is somewhat similar, but more complex; chronic pain?
• applications of the ultrasound beyond ablation, by using mechanical effects (e.g. opening a transient leak of the blood brain barrier for focal drug delivery; or sonothrombolysis; or neuromodulation)
• 2015 paper on "sonogentics" - neuromodulation of brain activity in C. elegans through genetic insertion of a mechanosensitive ion channel
• Q from audience: since you're doing ablation, has focused ultrasound been explored for cancer?
  • A: it's a focusing issue - focused ultrasound works best in the center of the brain, but most brain cancers are in or near the cortex

[Daniel-Mietchen]

I did not attend the symposium yesterday and am finalizing a report while listening to the talks today, so not taking notes much.

[Daniel-Mietchen]

Some observations from this morning:

• interesting work on sleep-wake patterns and the development of Alzheimers mentioned by David Holtzman
  • summary: https://twitter.com/EvoMRI/status/1134465152877654016
  • will work a bit on related Scholia profiles later (could not do that right now)
  • https://tools.wmflabs.org/scholia/author/Q56827171
  • https://tools.wmflabs.org/scholia/topics/Q35831,Q11081
• Interesting slide in John Lukens' presentation about mice in X mazes where one arm is open, the other close
  • wildtype mice explore both arms but prefer the closed one
  • aim2 mutants basically do not venture into the open arm
• Some student of John Lukens (Ashley Bolte?) is to leave in two weeks to start a graduate degree in data science, and he hopes for further interaction with her

[Daniel-Mietchen]

Jonathan Kipnis (Scholia) also mentions an X maze experiment ("Alves De Lima et al., in Preparation") in mice where a variant (IL-17?) makes them less anxious, overconfident

[Daniel-Mietchen]

in the Q & A, Kipnis mentioned that they have looked into imaging lymphatic vessels via MRI but the frame rate was not useful for their purposes.

[Daniel-Mietchen]

In closing, Jaideep Kapur of the Brain Institute that organized the event mentioned that each session was organized by a different person, from a different unit across Grounds. Perhaps DSI should do one at the next shinding.

[Daniel-Mietchen]

I briefly spoke to Jaideep afterwards, and he said he'd be interested in a data-centric at the next shinding (which he expects to take place in about two years), and that he expects to run a neuro-focused session at this year's Datapalooza.

Also had a brief chat with John Lukens about continuous engagement with that student.

[Daniel-Mietchen]

• Tweets on the event%20OR%20braininstitute%20OR%20uvabrain%20OR%20brainsymposium%20OR%20uva_brain)