ArticleNature communications2022
Optimal deep brain stimulation sites and networks for stimulation of the fornix in Alzheimer's disease.
2 registry-linked trialsOpen access · goldAbstract read
In one paragraph
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 59 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed, 1 pooled it
10.7field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Modulation of Cognitive Function Using Electrical Brain Stimulation in Patients With Early Alzheimer Disease
A Twelve Month Double-blind Randomized Controlled Feasibility Study to Evaluate the Safety, Efficacy and Tolerability of Deep Brain Stimulation of the Fornix (DBS-f) in Patients With Mild Probable Alzheimer's Disease
Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Deep brain stimulation of the fornix for Alzheimer's disease: A systematic review and meta-analysis of cognitive outcomes.Neurosurgical review · 2026Pooled it
- Bed nucleus of the stria terminalis-nucleus accumbens stimulation for depression: A randomized, double-blind, crossover trial.Cell reports. Medicine · 2026Trial
- Linking Invasive and Noninvasive Brain Stimulation in Parkinson's Disease: A Randomized Trial.Movement disorders : official journal of the Movement Disorder Society · 2024Trial
- Different functional connectivity gradients reflect aging and Alzheimer's disease.Nature neuroscience · 2026Article
- Integrating neural decoding, memristive materials, and adaptive control frameworks for next-generation hippocampal memory prosthetics.iScience · 2026Review
- Mechanism and progress of deep brain stimulation in the treatment of neurological and psychiatric disorders.MedScience · 2026Review
- High-frequency visual stimulation can increase medial temporal lobe ripple oscillation density.Communications medicine · 2026Article
- Subthalamic nucleus deep brain stimulation connectivity related to apathy outcomes in Parkinson's disease.Journal of Parkinson's disease · 2026Article
- Next-Generation Neuromodulation for Anxiety: Circuit-Based and Personalized Approaches.Current psychiatry reports · 2026Review
- Multimodal Image Guidance in Subthalamic Deep Brain Stimulation for Parkinson's Disease.Annals of neurology · 2026Article
- Circuit response to neuromodulation characterized with simultaneous deep brain stimulation and precision neuroimaging in humans.Nature neuroscience · 2026Article
- Direct electrical stimulation of the human amygdala enhances recognition memory for objects but not scenes.Communications biology · 2026Article
- Causal relationships between alzheimer's disease genetics and brain connectivity alterations: a multi-modal mendelian randomization study with transcriptomic validation of 191 rs-fMRI and 635 DTI neuroimaging traits.Brain imaging and behavior · 2026Article
- Optimal Deep Brain Stimulation Locations for Gilles de la Tourette Syndrome.medRxiv : the preprint server for health sciences · 2026Article
- Mapping the Cross-species Brain Connectivity Atlas and Hemispheric Asymmetry of the Temporal Pole in Humans and Macaques.Neuroscience bulletin · 2026Article
- Cognition, Diagnosis, and Treatment of Alzheimer's Disease: A Review.Recent patents on biotechnology · 2026Review
- Translational prospectives for deep brain stimulation and low-intensity focused ultrasound neuromodulation: IFCN Handbook chapter.Clinical neurophysiology practice · 2026Review
- Hyperdirect projections from the supplementary motor area mediate subthalamic stimulation effects on movement initiation and inhibition in Parkinson's disease.Brain communications · 2026Article
- White matter resection and verbal memory deficits after temporal lobe epilepsy surgery.Brain communications · 2026Article
- A Multi-Symptom Circuit Architecture of Obsessive-Compulsive Disorder.medRxiv : the preprint server for health sciences · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
32 authors at 13 institutions in 3 countries.
Ana Sofía RíosMovement Disorder and Neuromodulation Unit, Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Simón OxenfordMovement Disorder and Neuromodulation Unit, Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.ORCID 0000-0003-2989-3861
Clemens NeudorferMovement Disorder and Neuromodulation Unit, Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Konstantin ButenkoMovement Disorder and Neuromodulation Unit, Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Ningfei LiMovement Disorder and Neuromodulation Unit, Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.ORCID 0000-0003-3315-3591
Nanditha RajamaniMovement Disorder and Neuromodulation Unit, Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Alexandre BoutetDivision of Neurosurgery, Department of Surgery, University Health Network and University of Toronto, Toronto, ON, M5T2S8, Canada.ORCID 0000-0001-6942-5195
Gavin J B EliasDivision of Neurosurgery, Department of Surgery, University Health Network and University of Toronto, Toronto, ON, M5T2S8, Canada.ORCID 0000-0002-7495-550X
Jurgen GermannDivision of Neurosurgery, Department of Surgery, University Health Network and University of Toronto, Toronto, ON, M5T2S8, Canada.ORCID 0000-0003-0995-8226
Aaron LohDivision of Neurosurgery, Department of Surgery, University Health Network and University of Toronto, Toronto, ON, M5T2S8, Canada.
Wissam DeebUMass Chan Medical School, Department of Neurology, Worcester, MA, 01655, USA.
Fuyixue WangAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Harvard Medical School, Massachusetts General Hospital, Charlestown, MA, USA.ORCID 0000-0001-8975-2775
Kawin SetsompopAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Harvard Medical School, Massachusetts General Hospital, Charlestown, MA, USA.
Bryan SalvatoUniversity of Florida Health Jacksonville, Jacksonville, FL, USA.
Leonardo Brito de AlmeidaNorman Fixel Institute for Neurological Diseases, Departments of Neurology and Neurosurgery, University of Florida, Gainesville, FL, USA.
Kelly D FooteNorman Fixel Institute for Neurological Diseases, Departments of Neurology and Neurosurgery, University of Florida, Gainesville, FL, USA.ORCID 0000-0002-2436-4138
Robert AmaralCerebral Imaging Centre, Douglas Research Centre, Montreal, QC, Canada.
Paul B RosenbergDepartment of Psychiatry and Behavioral Sciences and Richman Family Precision Medicine Center of Excellence, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
David F Tang-WaiKrembil Research Institute, University of Toronto, Toronto, ON, M5T2S8, Canada.
David A WolkDepartment of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
Anna D BurkeBarrow Neurological Institute, Phoenix, AZ, USA.
Stephen SallowayDepartment of Psychiatry and Human Behavior and Neurology, Alpert Medical School of Brown University, Providence, RI, USA.ORCID 0000-0002-2631-0942
Marwan N SabbaghBarrow Neurological Institute, Phoenix, AZ, USA.
M Mallar ChakravartyCerebral Imaging Centre, Douglas Research Centre, Montreal, QC, Canada.
Gwenn S SmithDepartment of Psychiatry and Behavioral Sciences and Richman Family Precision Medicine Center of Excellence, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0003-0706-5440
Constantine G LyketsosDepartment of Psychiatry and Behavioral Sciences and Richman Family Precision Medicine Center of Excellence, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Michael S OkunNorman Fixel Institute for Neurological Diseases, Departments of Neurology and Neurosurgery, University of Florida, Gainesville, FL, USA.ORCID 0000-0002-6247-9358
William S AndersonJohns Hopkins School of Medicine, Baltimore, MD, USA.ORCID 0000-0003-0958-050X
Zoltan MariJohns Hopkins School of Medicine, Baltimore, MD, USA.ORCID 0000-0003-0356-9879
Francisco A PonceBarrow Neurological Institute, Phoenix, AZ, USA.
Andres M LozanoDivision of Neurosurgery, Department of Surgery, University Health Network and University of Toronto, Toronto, ON, M5T2S8, Canada.ORCID 0000-0001-8257-3694
Andreas HornMovement Disorder and Neuromodulation Unit, Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany. ahorn1@bwh.harvard.edu.ORCID 0000-0002-0695-6025
Humboldt-Universität zu Berlin · DEUniversity Health Network · CAJohns Hopkins University · USBarrow Neurological Institute · USUniversity of Florida · USHarvard University · USBrigham and Women's Hospital · USCleveland Clinic · USMcGill University · CAProvidence College · USUMass Memorial Health Care · USUniversity of Florida Health · USUniversity of Pennsylvania · US
Funding
Research Education ComponentP30AG066507 · NIA · JOHNS HOPKINS UNIVERSITY · PI MARILYN S. ALBERT · 2020 to 2026
$29.3MResearch Education ComponentP30AG072979 · NIA · UNIVERSITY OF PENNSYLVANIA · PI DAVID A WOLK · 2021 to 2026
$24.8MUsing human brain connectivity to identify the causal neuroanatomical substrate of depression symptomsR01MH113929 · NIMH · BRIGHAM AND WOMEN'S HOSPITAL · PI MICHAEL D FOX · 2017 to 2026
$6.9MToward Connectomic Deep Brain Stimulation in Obsessive Compulsive DisorderR01MH130666 · NIMH · BRIGHAM AND WOMEN'S HOSPITAL · PI MICHAEL D FOX · 2022 to 2026
$3.9MUsing Brain Lesions and Deep Brain Stimulation to Identify an Epilepsy CircuitR01NS127892 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI MICHAEL D FOX · 2022 to 2026
$3.4MNIA NIH HHS P30 AG066507NIA NIH HHS P30 AG072979NIMH NIH HHS R01 MH113929NIMH NIH HHS R01 MH130666NINDS NIH HHS R01 NS127892
Abstract
Deep brain stimulation (DBS) to the fornix is an investigational treatment for patients with mild Alzheimer's Disease. Outcomes from randomized clinical trials have shown that cognitive function improved in some patients but deteriorated in others. This could be explained by variance in electrode placement leading to differential engagement of neural circuits. To investigate this, we performed a post-hoc analysis on a multi-center cohort of 46 patients with DBS to the fornix (NCT00658125, NCT01608061). Using normative structural and functional connectivity data, we found that stimulation of the circuit of Papez and stria terminalis robustly associated with cognitive improvement (R = 0.53, p < 0.001). On a local level, the optimal stimulation site resided at the direct interface between these structures (R = 0.48, p < 0.001). Finally, modulating specific distributed brain networks related to memory accounted for optimal outcomes (R = 0.48, p < 0.001). Findings were robust to multiple cross-validation designs and may define an optimal network target that could refine DBS surgery and programming.
Indexed as
Alzheimer DiseaseDeep Brain StimulationBrainFornix, BrainHumansRandomized Controlled Trials as TopicThalamus
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY
Read underepoch 390
Registered trials
NCT00658125ClinicalTrials.gov
NCT01608061ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.