chalk talk

NSEEC industry.

Bickle foundation. high risk high reward.

NSERC grant. Cross-modal measurement of in-vivo spiking activities from the known cell-types (Neural recoding + analysis)

Aim1. Develop cross-modal electrophysiology recording and stimulation capability combined with optical recording and stimulation at the brain-wide, cellular resolution.

polymer microelectrodes, microLED, transparent glass electrodes, multifunctional probes

Aim2. Generate electro-optical groundtruth recordings by tracking the spiking activities of known cell types over multiple days, and use them to validate existing spike sorting and Ca image analysis algorithms.

Aim3. Develop online analysis software to analyze the electrical and optical recordings in real-time.

Implement algorithms using real-time OS, FPGA, and


NSERC grant. Develop AI-based predicitve neuroinformatics platform for distributed computing environment

Aim 1. Develop web-based platform to benchmark existing neural decoding algorithms using publicly available neural recordings paired with behavioral or sensory recordings.

Based on SpikeForest pipeline in collaboration with Flatiron Institute. Combines calcium imaging analysis, spike sorting analysis, behavioral analysis. Uses IBL and Allen brainobservatory dataset

Aim 2. Develop algorithms to predict voluntary decisions animals make during spatial navigations using existing datasets.

T-maze. W-maze. accuracy and predictive time window evaluation. LFP and spiking information. phase

CIHR grant. Neurodynamics during social functions in normal and autistic brains

I am interested in studying synchronized neurodynamics in a pair of socially interacting animals under naturalistic conditions.
In particular, I want to understand how social behaviours are perceived and generated in distributed brain areas including the auditory and motor cortex, amygdala, and hippocampus.
Mice vocalize at ultrasonic frequencies and I want to investigate how various communication signals play a role in synchronizing neural states in healthy individuals as well as a mouse autism model [6].
The understanding gained from this research may reveal novel biological markers for autism spectrum disorder (ASD) based on key factors distinguishing autistic and healthy brains in perceiving and expressing vocal communication.
In addition, long-term neural recordings in multiple brain regions could reveal a circuit-level action of pharmacological agents such as R-Baclofen, which has been recently developed and clinically evaluated to treat the symptoms of ASD.
One of the hallmarks of ASD is an enhanced ability to recognize fine perceptual details while missing out on a larger context.
By using ultrasonic vocalization as a behavioural assay, I want to measure how various stages of sensory (auditory) information processing are affected by ASD and understand the action of R-Baclofen in inducing neuroplasticity over an extended period.
Recently, functional brain stimulation is beginning to replace pharmacological treatments for various neurological conditions including Parkinson’s disease, epilepsy, and depression to overcome drug resistance and unintended side effects.
Based on understanding the circuit-level mechanism of R-Baclofen, I want to explore targeted neurostimulation to achieve similar effects in the animal models of ASD.
My initial approach would be to apply a machine-learning driven bidirectional neural interface to detect and interfere with pathological neurodynamics as well as to induce neuroplasticity that affects the resting brain state.

Multimodal brain activity measurement papers

Multimodal Characterization of Neural Networks Using Highly Transparent Electrode Arrays

Euisik yoon group Mendrela thesis

Optogenetic-fMRI arousal networks

Ottawa small animal MRI: see Georg Northoff
Syringe-injectable mesh electrodes (Lieber group)

EEG and fMRI (thesis) sleep deprevation 2018
Simultaneous gcamp+fMRI (2017)

Diversity of sharp-wave–ripple LFP signatures reveals differentiated brain-wide dynamical events (2015)

# Theory
Variational inference (David Blei). Edwardlib.org

# Neuroscience research funding
https://can-acn.org/neuroscience-research-funding-opportunities

Funding applications

# Canadian funding
researchnet.ca
NSERC discovery grant: Aug1 notification of intent, Nov 1 application
NSERC CREATE Grant: Collaborative research and trainig experience training. $1.65M for 6 years
Compute Canada: Nov 8
NSERC discovery grant: Aug1 notification of intent, Nov 1 application
NSERC CREATE Grant: Collaborative research and trainig experience training. $1.65M for 6 years
Albertainnovates.ca:
DND/NSERC grant:
NSERC CREATE
NSERC research tools and instruments: 150K (OCT 25)
NSERC training video
CIHR grants (researchnet)
CFI grant
New frontiers in research fund (international, fall 2019). (Exploration Aug 7, Sep 4. $125K/year, 2 years)
New Frontiers Transformation (2019 competition)

# Private funding
Simons foundation: Winter 2020 pilot. $300K for two years. Sep 13. New to autism.
Simons Bridge to independence. $500K for 3 years. LOI due Aug 8 2020.

CZI: https://chanzuckerberg.com/rfa/essential-open-source-software-for-science/ (closed on Aug 1)
250K for 1 year
HHMI
KECK foundation:

# US Grants
Participation by Canadian Researchers in the NIH BRAIN Initiative
Team Grant : Next Generation Networks for Neuroscience (NeuroNex) from CIHR and NSF (2019 Dec 13)

# EU grants
https://www.neuron-eranet.eu/en/196.php
https://www.hfsp.org/funding/hfsp-funding/research-grants (Mar18)

# Neuropixels resources
Neuropixels from cortex lab
https://github.com/cortex-lab/neuropixels/wiki/Equipment_List
https://www.neuropixels.org/

International brain lab
https://github.com/int-brain-lab/iblrig

# Chronic implementation

Neuropixels chronic implantation
https://www.biorxiv.org/content/10.1101/406074v1.full

# Chronic surgery
MRI compatible CMOS
https://ieeexplore.ieee.org/abstract/document/8116684
Tim Hanson’s neural sewing machine
https://www.biorxiv.org/content/10.1101/578542v1
https://www.biorxiv.org/content/10.1101/578542v1
Power of small animal fMRI

https://www.frontiersin.org/articles/10.3389/fphar.2015.00231/full
#Reverse engineering visual intelligence (Jim DiCarlo)
https://www.youtube.com/watch?v=3djQSX1FJ9I
Using goal-driven deep learning models to understand sensory cortex

Figure 1

# Intel Telluride Neuromorphic cognition engineering workshop
3-week hand-on work
https://sites.google.com/view/telluride2019/about-workshop?authuser=0

# MRI compatibility of pacemaker

ok according to Harvard Men’s health watch
MRI safe metals: copper, cobalt-chromium, Titanium, stainless-steel
MRI-compatible flexible probe: SU-8 side protect, polyimide based, titanium as mask for SU-8

Don’t forget to check out http://m8ta.com/ (Tim Hanson’s article collections)

R-CHOP + and High-Dose Methotrexate (HM)

Article 1: CHOP-R and High-Dose Methotrexate In The Primary CNS Lymphoma Revisited. 10-Year Experience and 92 Patients From a Single Institution (2013)

Article 2: Patient Selection for High-Dose Methotrexate As Central Nervous System Prophylaxis in Diffuse Large B-Cell Lymphoma in Australia: Are We Getting It Right?

Conclusions: HDMTX was well-tolerated by patients, therefore can safely be administered as CNS prophylaxis under current hospital protocols. Application of the DSHNHL prognostic model identifies a different population of candidates for CNS prophylaxis compared to historical risk factors and may lead to better patient selection for this intervention

Article 3: Addition of high-dose methotrexate to standard treatment for patients with high-risk diffuse large B-cell lymphoma contributes to improved freedom from progression and survival but does not prevent central nervous system relapse

Combination of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) is regarded as standard care for diffuse large B-cell lymphoma (DLBCL) and upfront intensification of therapy is still controversial. The current study aimed to dertermine whether the addition of high-dose methotrexate (HDMTX) affects long-term outcomes and could also prevent central nervous system (CNS) relapse. Medical records of 480 patients with DLBCL treated between 1994 and 2013 at Rambam and Hadassah medical centers in Israel were reviewed; 130 (27%) had received HDMTX. Patients receiving HDMTX generally had higher International Prognostic Index (IPI) and CNS-IPI scores. HDMTX addition significantly improved progression free and overall survival (p = .001) and this advantage was maintained in multivariate analysis (HR for OS 0.3; 95% CI 0.19-0.47; p < .0001). Thirty-one (6.5%) patients had CNS relapse and in these cases high CNS-IPI, but not HDMTX treatment, was independently associated with CNS relapse (HR 1.2; 95% CI 1.2-11.5; p = .02). In conclusion, the addition of HDMTX to CHOP/RCHOP independently and significantly improved prognosis of patients with high-risk DLBCL, irrespective of their risk for CNS relapse.

Methotrexate

Side effects needing medical attention
Black, tarry stools; bloody vomit; diarrhea; sores in mouth or on lips; stomach pain; fever; chills; sore throat; unusual bleeding or bruising; blood in urine or dark urine; blurred vision; confusion; convulsions or seizures; cough; dizziness; drowsiness; headache; joint pain; shortness of breath; rash; swelling of feet or lower legs; unusual tiredness or weakness; yellowing of eyes and skin; loss of appetite; nausea or vomiting. The above side effects may be more likely to occur in very young and very old patients.

Side effects needing medical attention after stopping this medication
Blurred vision; convulsions or seizures; dizziness; drowsiness; headache; confusion; unusual tiredness or weakness.

Major side effects of low-dose methotrexate

Joel M Kremer, MDSection Editor:James R O’Dell, MDDeputy Editor:Paul L Romain, MD
INTRODUCTION

Methotrexate (MTX) use can be associated with a variety of adverse effects over a wide range of severity; the risk of most side effects is influenced by the MTX dose and treatment regimen. In rheumatoid arthritis (RA) and other disorders, MTX is administered as long-term, low-dose therapy, usually 7.5 to 25 mg weekly, unlike its use for treatment of malignant disease, where it is may be administered in a cyclic fashion in doses of 1 gram or more.
The most commonly observed side effects of MTX at doses typically used for the treatment of RA are rarely life-threatening, in contrast with the high doses used in the treatment of malignancies. Nevertheless, they may become clinically significant if they result in premature discontinuation or dose alteration of a drug that is the best therapeutic alternative for a given individual.

Potentially life-threatening hepatotoxicity, pulmonary damage, and myelosuppression may be seen with use of MTX as either high- or low-dose therapy, while nephrotoxicity is a manifestation of high-dose therapy that occurs rarely, if ever, with low-dose MTX treatment.

The major side effects of low-dose MTX are reviewed here. The use of low-dose MTX in patients with RA and other rheumatic diseases and the clinical use and adverse effects of high-dose MTX and related adverse effects are described separately. (See “Use of methotrexate in the treatment of rheumatoid arthritis” and “Therapeutic use and toxicity of high-dose methotrexate”.)