Brain structures and networks responsible for stimulation-induced memory flashbacks during forniceal deep brain stimulation for Alzheimer's disease
Introduction: Fornix deep brain stimulation (fx-DBS) is under investigation for treatment of Alzheimer's disease (AD). We investigated the anatomic correlates of flashback phenomena that were reported previously during acute diencephalic stimulation. Methods: Thirty-nine patients with mild AD who took part in a prior fx-DBS trial (NCT01608061) were studied. After localizing patients’ implanted electrodes and modeling the volume of tissue activated (VTA) by DBS during systematic stimulation testing, we performed (1) voxel-wise VTA mapping to identify flashback-associated zones; (2) machine learning–based prediction of flashback occurrence given VTA overlap with specific structures; (3) normative functional connectomics to define flashback-associated brain-wide networks. Results: A distinct diencephalic region was associated with greater flashback likelihood. Fornix, bed nucleus of stria terminalis, and anterior commissure involvement predicted memory events with 72% accuracy. Flashback-inducing stimulation exhibited greater functional connectivity to a network of memory-evoking and autobiographical memory-related sites. Discussion: These results clarify the neuroanatomical substrates of stimulation-evoked flashbacks.
Alzheimer's and Dementia
Digital Object Identifier (DOI)
Germann, Jürgen; Elias, Gavin J.B.; Boutet, Alexandre; Narang, Keshav; Neudorfer, Clemens; Horn, Andreas; Loh, Aaron; Deeb, Wissam; Salvato, Bryan; Almeida, Leonardo; Foote, Kelly D.; Rosenberg, Paul B.; Tang-Wai, David F.; Wolk, David A.; Burke, Anna D.; Salloway, Stephen; Sabbagh, Marwan N.; Chakravarty, M. Mallar; Smith, Gwenn S.; Lyketsos, Constantine G.; Okun, Michael S.; and Lozano, Andres M., "Brain structures and networks responsible for stimulation-induced memory flashbacks during forniceal deep brain stimulation for Alzheimer's disease" (2021). Neurology. 658.