Leon A Steiner, David Crompton, Srdjan Sumarac, Artur Vetkas, Jürgen Germann, Maximilian Scherer, Maria Justich, Alexandre Boutet, Milos R Popovic, Mojgan Hodaie, Suneil K Kalia, Alfonso Fasano, William D Hutchison Wd, Andres M Lozano, Milad Lankarany, Andrea A Kühn, Luka Milosevic
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) produces an electrophysiological signature called evoked resonant neural activity (ERNA); a high-frequency oscillation that has been linked to treatment efficacy. However, the single-neuron and synaptic bases of ERNA are unsubstantiated. This study proposes that ERNA is a subcortical neuronal circuit signature of DBS-mediated engagement of the basal ganglia indirect pathway network. In people with Parkinson's disease, we: (i) showed that each peak of the ERNA waveform is associated with temporally-locked neuronal inhibition in the STN; (ii) characterized the temporal dynamics of ERNA; (iii) identified a putative mesocircuit architecture, embedded with empirically-derived synaptic dynamics, that is necessary for the emergence of ERNA in silico; (iv) localized ERNA to the dorsal STN in electrophysiological and normative anatomical space; (v) used patient-wise hotspot locations to assess spatial relevance of ERNA with respect to DBS outcome; and (vi) characterized the local fiber activation profile associated with the derived group-level ERNA hotspot...
April 11, 2024: Nature Communications