Techniques Development

Importance of the DARPA Grant for tech development

Audacious goal is to create a TMS protocol that within a day eliminates suicidality, reducing what now takes about 6 weeks and 36 treatments into one day

Pushing the limit on:

Where to target (within individual networks, advanced neuronav)
What the brain is doing during stimulation (cognitive tasks, EEG phase)
How to determine response (EEG entrainment, cortical excitability), EEG and fNIRS to check response over time and adjust
Closed loop adjustments in realtime

DARPA wants this to benefit and supercharge the field. We are thus working with vendors to create plug and play systems that other researchers and clinicians can purchase and use. Insights and knowledge will quickly cross fertilize to other areas like stroke

TMS Targeting vs Therapeutic Targeting

Hypothesis: the level of neural activation induced by TMS in areas distal to direct TMS stimulation is dependent on the instantaneous brain state (e.g. alpha phase) when the pulse(s) is applied

Simultaneous fMRI-EEG-TMS (fET)

Why is TMS/fMRI Important for Rehab?

To date TMS has not proven highly successful in stroke rehab clinical trials.
The field lacks critical information about TMS locations and dosing that might translate therapeutically.
Where do we position the coil (ipsilesional, contralesional, perilesional) with what intensity, to best engage circuits needed for recovery?
Doing TMS in the scanner allows for direct testing of locations and TMS parameters that are then important for effective clinical trials.
For example, TMS/fMRI was critical in developing TMS for treating depression, identifying prefrontal cortical locations that then interacted with subcortical nodes (Anterior Cingulate Gyrus) for effective treatment.
Doing this for stroke rehab is important, and more challenging as each individual stroke patient has varying anatomy and connections.

fNIRS-EEG-TMS (fNET)

E-Field Modeling

Target Engagement with e-field is now the standard!

Overarching Goal of E-Field Modeling Technology Development

Overarching Hypothesis: tDCS will not develop into a treatment until we understand how to individually adjust the dose.

Goal: To develop a personalized method of applying transcranial direct current stimulation (tDCS) and test whether it improves response

Electric field (E-field) modeling: Uses structural MRI scans and tissue conductivities to simulate tDCS (and TMS) stimulation

A reexamination of motor and prefrontal TMS in tobacco use disorder: Time for personalized dosing based on electric field modeling?

E-field modeling is helping with all forms of brain stimulation, not just tDCS

E.g TMS e-field mattered in the recent TMS Sync depression trial
All subjects were treated at 120% of MT, but post study analysis (Caulfield) found there were still large differences in distance, AND this Mattered
Argues for need for individualized personalized dose

Closed loop taVNS in CIMT

Sophisticated Vagus Nerve Stimulation

Organ- and function-specific anatomical organization of vagal fibers supports fascicular vagus nerve stimulation

Will many medications be replaced by end organ targeted VNS?

Targeted neuroplasticity with time locked VNS and rehab

Recent Invasive Microtransponder trial and FDA approval
Noninvasive stimulation through neck or ear (taVNS)
- Paired taVNS to enhance bottle feeding in newborns failing oral feeding (Jenkins, PI)
  - RCT underway
- What about infants and children with CP?
  - ?pair with CIMT?
  - Ongoing study by McGloon, Coker-Bolt and colleagues