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In Alzheimer's & dementia : the journal of the Alzheimer's Association

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.

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, Lozano Andres M


“Alzheimers disease”, brain connectivity, deep brain stimulation, fornix, magnetic resonance imaging, memory