Authors :
First Author: Emma ACERBO, PhD – Emory University
Presenting Author: Adam Williamson, PhD – International Clinical Research Center
Emma ACERBO, PhD – Emory University; Boris Botzanowski, PhD – Emory University; Damian Dellavale, PhD – Aix Marseille Université; Matthew Stern, MS – Emory University; Eric Cole, MS – Emory University; Daniel Drane, PhD – Emory University; Robert Gross, MD, PhD – Emory University; Adam Williamson, PhD – Aix Marseille Université
Rationale:
Electrical stimulation mapping plays a crucial role in epilepsy research by delivering stimulation pulses to evoke responses in brain tissue. It can be performed using electrodes implanted through stereoelectroencephalography or by placing grids on the cortex (electrocorticography, ECoG). These stimulations help determine if the region that the neurosurgeon potentially needs to remove (in the context of epileptic focus resection) is surrounded by eloquent cortex, meaning tissue critical for high-level functions such as language and memory. However, deviations in electrode placement may prevent the intended stimulation or reveal involvement of an unplanned region without an implanted electrode. To address these challenges, we utilized temporal interference (TI), a completely non-invasive deep brain stimulation method. Traditional TI applies high-frequency sine waves ( >1 kHz, f1 & f2) through external electrodes, generating a low-frequency amplitude modulation (Δf) to target deep brain regions. However, classic TI lacks the ability to deliver bursts of pulses. In this work, we modified the classic TI method by replacing the sine waveform with phase-shift keying modulated signals, enabling the creation of pulsed stimulations (spTI) in a non-invasive manner.
Methods:
We conducted surgical procedures on awake and anesthetized mice (n=12), implanting minimally invasive screws and depth probes for stimulation and recording purposes. Two-photon imaging was used to visualized neuronal responses to TI amplitude modulation (Δf). Stimulation depth profiles were compared between classic TI and spTI in anesthetized mice using a 32-channel electrode in the hippocampus. Furthermore, stimulation was performed on freely behaving animals to determine the current required to evoke afterdischarges (f1=1200Hz & f2=1250Hz,Δf=50Hz) .
Results:
Our results demonstrate that neuronal activation follows the frequency of TI amplitude modulation (Δf). It is the first evidence that the network is actually activated at the Δf frequency. We observed comparable depth profiles of stimulation between classic TI and spTI in anesthetized mice. Additionally, using a kindling mouse model, we found that spTI can evoke afterdischarges similar to classic TI, with potential increased efficacy (p-value**=0.005).
Conclusions:
In conclusion, our experiments have shown the feasibility of creating non-invasive pulsed stimulation based on TI. We have demonstrated that spTI not only replicates the effects of classic TI but may even be more effective. This novel stimulation paradigm holds promise for exploring brain structures that are not directly implanted but require exploration prior to resection or ablation procedures.
Funding:
This research was supported by funds from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement starting grant No. 716867 and POC No 963976).