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Brain structures and networks responsible for stimulation‐induced memory flashbacks during forniceal deep brain stimulation for Alzheimer's disease
Author(s) -
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.,
TangWai 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.,
Lozano Andres M.
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.12238
Subject(s) - fornix , flashback , neuroscience , deep brain stimulation , psychology , stimulation , stria terminalis , anterior commissure , prefrontal cortex , neuropsychology , hippocampus , amygdala , medicine , disease , cognition , parkinson's disease , chemistry , combustor , organic chemistry , combustion
Abstract 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.