Brain structures and networks responsible for stimulation-induced memory flashbacks during forniceal deep brain stimulation for Alzheimer's disease

Alzheimers Dement. 2021 May;17(5):777-787. doi: 10.1002/alz.12238. Epub 2021 Jan 21.


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.

Keywords: Alzheimer's disease; brain connectivity; deep brain stimulation; fornix; magnetic resonance imaging; memory.

MeSH terms

  • Aged
  • Alzheimer Disease / therapy*
  • Brain
  • Deep Brain Stimulation*
  • Female
  • Fornix, Brain*
  • Humans
  • Machine Learning
  • Magnetic Resonance Imaging
  • Male
  • Memory / physiology*