Jaya L Padmanabhan1, Danielle Cooke2, Juho Joutsa3, Shan H Siddiqi4, Michael Ferguson2, R Ryan Darby5, Louis Soussand2, Andreas Horn6, Na Young Kim7, Joel L Voss8, Andrew M Naidech8, Amy Brodtmann9, Natalia Egorova9, Sophia Gozzi10, Thanh G Phan10, Maurizio Corbetta11, Jordan Grafman12, Michael D Fox13. 1. Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Berenson-Allen Center for Non-Invasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Division of Cognitive Neurology, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. Electronic address: jayapad@gmail.com. 2. Berenson-Allen Center for Non-Invasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. 3. Berenson-Allen Center for Non-Invasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Department of Neurology, University of Turku, Turku, Finland; Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland. 4. Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Berenson-Allen Center for Non-Invasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Division of Cognitive Neurology, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Division of Neurotherapeutics, McLean Hospital, Harvard Medical School, Boston, Massachusetts; Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland. 5. Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee. 6. Movement Disorders and Neuromodulation Unit, Department of Neurology, Charité-University Medicine Berlin, Berlin, Germany. 7. Berenson-Allen Center for Non-Invasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. 8. Ken and Ruth Davee Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Department of Medical Social Sciences, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. 9. Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia; Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Victoria, Australia. 10. School of Psychological Sciences, Department of Medicine, Monash University, Melbourne, Victoria, Australia; Stroke and Aging Research Group, School of Clinical Sciences, Department of Medicine, Monash University and Stroke Unit, Monash Medical Centre, Melbourne, Victoria, Australia. 11. Department of Neuroscience, University of Padova and Padova Neuroscience Center, Padova, Italy; Departments of Neurology, Radiology, Bioengineering, and Neuroscience, Washington University School of Medicine, Saint Louis, Missouri. 12. Psychiatry and Behavioral Sciences and Cognitive Neurology/Alzheimer's Disease Research Center, Feinberg School of Medicine and Department of Psychology, Northwestern University, Chicago, Illinois; Shirley Ryan AbilityLab, Chicago, Illinois. 13. Berenson-Allen Center for Non-Invasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Division of Cognitive Neurology, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. Electronic address: foxmdphd@gmail.com.
Abstract
BACKGROUND: Focal brain lesions can lend insight into the causal neuroanatomical substrate of depression in the human brain. However, studies of lesion location have led to inconsistent results. METHODS: Five independent datasets with different lesion etiologies and measures of postlesion depression were collated (N = 461). Each 3-dimensional lesion location was mapped to a common brain atlas. We used voxel lesion symptom mapping to test for associations between depression and lesion locations. Next, we computed the network of regions functionally connected to each lesion location using a large normative connectome dataset (N = 1000). We used these lesion network maps to test for associations between depression and connected brain circuits. Reproducibility was assessed using a rigorous leave-one-dataset-out validation. Finally, we tested whether lesion locations associated with depression fell within the same circuit as brain stimulation sites that were effective for improving poststroke depression. RESULTS: Lesion locations associated with depression were highly heterogeneous, and no single brain region was consistently implicated. However, these same lesion locations mapped to a connected brain circuit, centered on the left dorsolateral prefrontal cortex. Results were robust to leave-one-dataset-out cross-validation. Finally, our depression circuit derived from brain lesions aligned with brain stimulation sites that were effective for improving poststroke depression. CONCLUSIONS: Lesion locations associated with depression fail to map to a specific brain region but do map to a specific brain circuit. This circuit may have prognostic utility in identifying patients at risk for poststroke depression and therapeutic utility in refining brain stimulation targets.
BACKGROUND: Focal brain lesions can lend insight into the causal neuroanatomical substrate of depression in the human brain. However, studies of lesion location have led to inconsistent results. METHODS: Five independent datasets with different lesion etiologies and measures of postlesion depression were collated (N = 461). Each 3-dimensional lesion location was mapped to a common brain atlas. We used voxel lesion symptom mapping to test for associations between depression and lesion locations. Next, we computed the network of regions functionally connected to each lesion location using a large normative connectome dataset (N = 1000). We used these lesion network maps to test for associations between depression and connected brain circuits. Reproducibility was assessed using a rigorous leave-one-dataset-out validation. Finally, we tested whether lesion locations associated with depression fell within the same circuit as brain stimulation sites that were effective for improving poststroke depression. RESULTS: Lesion locations associated with depression were highly heterogeneous, and no single brain region was consistently implicated. However, these same lesion locations mapped to a connected brain circuit, centered on the left dorsolateral prefrontal cortex. Results were robust to leave-one-dataset-out cross-validation. Finally, our depression circuit derived from brain lesions aligned with brain stimulation sites that were effective for improving poststroke depression. CONCLUSIONS: Lesion locations associated with depression fail to map to a specific brain region but do map to a specific brain circuit. This circuit may have prognostic utility in identifying patients at risk for poststroke depression and therapeutic utility in refining brain stimulation targets.
Authors: Alexander L Cohen; Louis Soussand; Sherryse L Corrow; Olivier Martinaud; Jason J S Barton; Michael D Fox Journal: Brain Date: 2019-12-01 Impact factor: 13.501
Authors: Matthew J Burke; Juho Joutsa; Alexander L Cohen; Louis Soussand; Danielle Cooke; Rami Burstein; Michael D Fox Journal: Brain Date: 2020-02-01 Impact factor: 13.501
Authors: Nicholas E Souter; Xiuyi Wang; Hannah Thompson; Katya Krieger-Redwood; Ajay D Halai; Matthew A Lambon Ralph; Michel Thiebaut de Schotten; Elizabeth Jefferies Journal: Brain Struct Funct Date: 2022-07-04 Impact factor: 3.270
Authors: Gonçalo Cotovio; Daniel Talmasov; J Bernardo Barahona-Corrêa; Joey Hsu; Suhan Senova; Ricardo Ribeiro; Louis Soussand; Ana Velosa; Vera Cruz E Silva; Natalia Rost; Ona Wu; Alexander L Cohen; Albino J Oliveira-Maia; Michael D Fox Journal: J Clin Invest Date: 2020-10-01 Impact factor: 14.808
Authors: Shan H Siddiqi; Stephan F Taylor; Danielle Cooke; Alvaro Pascual-Leone; Mark S George; Michael D Fox Journal: Am J Psychiatry Date: 2020-03-12 Impact factor: 18.112
Authors: Stephan A Goerigk; Frank Padberg; Markus Bühner; Nina Sarubin; Tyler S Kaster; Zafiris J Daskalakis; Daniel M Blumberger; Lucas Borrione; Lais B Razza; Andre R Brunoni Journal: Neuropsychopharmacology Date: 2020-12-21 Impact factor: 7.853