Jürgen Germann1, Gavin J B Elias1, Alexandre Boutet1,2, Keshav Narang1, Clemens Neudorfer1, Andreas Horn3, Aaron Loh1, Wissam Deeb4, Bryan Salvato5, Leonardo Almeida4, Kelly D Foote4, Paul B Rosenberg6, David F Tang-Wai7, David A Wolk8, Anna D Burke9, Stephen Salloway10, Marwan N Sabbagh11, M Mallar Chakravarty12, Gwenn S Smith6, Constantine G Lyketsos6, Michael S Okun4, Andres M Lozano1. 1. Division of Neurosurgery, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Canada. 2. Joint Department of Medical Imaging, University of Toronto, Toronto, Canada. 3. Movement Disorders & Neuromodulation Unit, Department for Neurology, Charité - University Medicine Berlin, Berlin, Germany. 4. Norman Fixel Institute for Neurological Diseases, Departments of Neurology and Neurosurgery, University of Florida Health, USA. 5. Florida State University, USA. 6. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, USA. 7. Department of Neurology, Toronto Western Hospital, University Health Network, University of Toronto, Canada. 8. University of Pennsylvania, USA. 9. Department of Neurology, Barrow Neurological Institute, Phoenix, USA. 10. Department of Psychiatry and Human Behavior and Neurology, Alpert Medical School of Brown University, USA. 11. Cleveland Clinic Lou Ruvo Center for Brain Health, USA. 12. Douglas Mental Health University Research Institute, Canada.
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.
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.
Authors: Artur Vetkas; Jürgen Germann; Gavin Elias; Aaron Loh; Alexandre Boutet; Kazuaki Yamamoto; Can Sarica; Nardin Samuel; Vanessa Milano; Anton Fomenko; Brendan Santyr; Jordy Tasserie; Dave Gwun; Hyun Ho Jung; Taufik Valiante; George M Ibrahim; Richard Wennberg; Suneil K Kalia; Andres M Lozano Journal: Brain Commun Date: 2022-04-06
Authors: Clemens Neudorfer; Gavin J B Elias; Martin Jakobs; Alexandre Boutet; Jürgen Germann; Keshav Narang; Aaron Loh; Michelle Paff; Andreas Horn; Walter Kucharczyk; Wissam Deeb; Bryan Salvato; Leonardo Almeida; Kelly D Foote; Paul B Rosenberg; David F Tang-Wai; William S Anderson; Zoltan Mari; Francisco A Ponce; David A Wolk; Anna D Burke; Stephen Salloway; Marwan N Sabbagh; M Mallar Chakravarty; Gwenn S Smith; Constantine G Lyketsos; Michael S Okun; Andres M Lozano Journal: Brain Date: 2021-10-22 Impact factor: 13.501
Authors: Nardin Samuel; Artur Vetkas; Aditya Pancholi; Can Sarica; Aaron Loh; Jurgen Germann; Irene E Harmsen; Jordy Tasserie; Vanessa Milano; Kazuaki Yamamoto; Suneil K Kalia; Paul N Kongkham; Andres M Lozano Journal: Cancers (Basel) Date: 2021-12-05 Impact factor: 6.639