Rationale: Thalamic DBS is increasingly used for epilepsy, but stimulation paradigms remain largely empirical, with numerous adjustable parameters - amplitude, pulse width, frequency, and electrode configuration
1. Since treatment response is typically assessed using video-scalp EEG, understanding thalamo-cortical interactions is crucial for optimizing therapy and identifying biomarkers of efficacy.
Methods: Two patients, one (60/M) with ANT DBS for bitemporal epilepsy (L >R) and one (35/M) with CM DBS for LGS, were evaluated in the epilepsy monitoring unit. Simultaneous scalp EEG and DBS recordings were obtained during eyes open (EO), eyes closed (EC), hyperventilation (HV), and photic stimulation (Ph). Data analyzed for spectral power and band-wise functional connectivity (coherence and wPLI) between thalami and between each thalamus and scalp electrodes.
Results:
ANT patient (94.5 min): Normalized power was significantly higher in the left thalamus across all bands (δ: 0.65 vs 0.46, θ: 0.26 vs 0.30, α: 0.16 vs 0.27, β: 0.12 vs 0.20; p < 0.0001). Alpha power was higher during EO than EC (p < 0.0001). Inter-thalamic coherence peaked in the alpha band (0.63), followed by β > θ > δ (p < 0.0001), with coherence highest during HV (HV > EO > EC ≈ Ph). wPLI peaked in the delta band (0.60), followed by θ > α > β, also highest during HV (p < 0.0001). Thalamus-to-scalp coupling was strongest in the delta band: C4 > C3 > Cz (coherence) and C4 > Cz > Fz (wPLI) for both hemispheres.
CM patient (57 min): Right thalamus showed higher power in δ, θ, α bands; left had higher β (δ: 0.23 vs 0.25, θ: 0.32 vs 0.33, α: 0.34 vs 0.35, β: 0.35 vs 0.34; p < 0.001). Alpha power was higher during EO than EC (p < 0.0001). Inter-thalamic coherence was highest in the delta band (0.33) across EO, EC, HV; theta (0.34) during Ph (p < 0.001). wPLI followed δ > θ > α > β, with delta (0.30) highest during EO, EC, Ph and theta (0.36) during HV (p < 0.001). Thalamus-to-scalp coupling was strongest posteriorly and centrally: P8 > F4 > C3 (coherence) and P3 > P8 > Pz (wPLI) for left; C3 > P8 > O1 (coherence) and P4 > F4 > C4 (wPLI) for right.
Conclusions:
Spectral and connectivity analyses of ANT showed dominant delta power bilaterally (L > R), with strongest inter-thalamic coherence and wPLI in alpha and delta bands respectively. Thalamus-to-scalp coupling peaked in the delta band over central, and frontal regions, especially during HV.
CM exhibited symmetric power distribution across bands, with enhanced inter-thalamic connectivity in delta and theta bands. Thalamus-to-scalp coupling was strongest in the delta range over posterior, central, and frontal areas, notably during HV and Ph.
Alpha power was significantly higher during EO versus EC in both nuclei, in contrast with cortical alpha suppression with EO. These results highlight distinct spectral and connectivity profiles for ANT and CM, reflecting their differential roles in subcortical–cortical interaction in epilepsy.
1.Fasano A, Eliashiv D, Herman ST, Lundstrom BN, Polnerow D, Henderson JM, Fisher RS. Experience and consensus on stimulation of the anterior nucleus of thalamus for epilepsy. Epilepsia. 2021 Dec;62(12):2883-98.
Funding: Internally funded