Authors :
Presenting Author: Behnam Ghabel Damirchi, PhD Candidate – University of Texas at Arlington
Saeed Jahromi, Ph.D. Student – University of Texas at Arlington
Glykeria Sdoukopoulou, Ph.D. Student – University of Texas at Arlington
Sadra Shahdadian, Ph.D. – University of Texas at Arlington
Christos Papadelis, PhD – Cook Children's Health Care System
Rationale:
Transcranial temporal interference stimulation (tTIS) is a non-invasive neuromodulation technique capable of reaching deep brain structures by generating amplitude-modulated electric fields through interfering high-frequency currents. Unlike transcranial magnetic stimulation (TMS) or direct current stimulation (tDCS), which offer limited depth and spatial precision, tTIS leverages the brain’s low-pass filtering characteristics to enable more targeted and deeper stimulation. This study examines the potential of tTIS to non-invasively modulate ripple oscillations (100–170 Hz), which are increasingly recognized as biomarkers of epileptogenic zones, especially in pediatric drug-resistant epilepsy. Ripple activity plays a key role in pathological brain networks and seizure onset, making it a compelling target for therapeutic intervention. We assessed the focality, and efficacy of ripple-frequency tTIS using a pediatric head phantom modeled after a 3-year-old boy, with the goal of informing non-invasive treatment strategies for childhood epilepsy that could reduce reliance on invasive approaches like deep brain stimulation (DBS).
Methods:
A 3D-printed pediatric head phantom based on T1 MRI data replicated scalp, skull, and brain layers with conductivities of 0.33 S/m (scalp/brain) and 0.004 S/m (skull). Four dipolar electrodes were implanted in deep structures: right posterior orbital gyrus (R01, target), right dorsal cingulate cortex (R02), right cerebral white matter (R03), and left precuneus (L01). Stimulation was delivered via two electrode pairs (F7–PO7, F8–PO8) producing dual high-frequency sine wave offset to amplitude-modulate at 100 Hz (2,000/2,100 Hz), 120 Hz (2,000/2,120 Hz), and 170 Hz (2,000/2,170 Hz). Each trial lasted 25 s, divided into ten 2.5-second segments. Signals were recorded with a digital oscilloscope and analyzed offline in Brainstorm. After noise removal and filtering, Morlet wavelet time-frequency analysis extracted spectral power. One-tailed permutation t-tests with FDR correction (α = 0.05) compared target and control structures.
Results:
tTIS reliably induced ripple oscillations at the target (R01) across frequencies. At 100 Hz, R01 power significantly exceeded controls (R02: p=0.004; R03: p=0.002; L01: p=0.003). At 120 Hz, effects were similarly robust and localized (R02: p=0.004; R03: p=0.003; L01: p=0.003). At 170 Hz, power was slightly lower but still significant and specific (R02: p=0.005; R03: p=0.003; L01: p=0.003).Conclusions:
This study provides initial evidence that tTIS can safely and selectively induce ripple oscillations in the pediatric brain. The results highlight the method’s potential for achieving deep, frequency-specific modulation with high spatial precision. These findings lay the groundwork for future translational research aimed at developing non-invasive interventions for pediatric epilepsy.Funding:
This work was supported by the National Institute of Neurological Disorders and Stroke (R01NS104116; R01NS134944; Principal Investigator: Christos Papadelis).