Year: 2026
Type: preprint
Abstract: Lesion network mapping (LNM) and related techniques have been used in over 200 studies, primarily to test whether anatomically distributed lesions that cause the same symptom fall within a common brain network. A recent article 1 challenges the specificity and validity of this technique, suggesting that lesion network maps primarily reflect intrinsic properties of the normative connectome rather than lesion–symptom relationships. However, the data and procedures in van den Heuvel et al. do not reflect those used in most LNM studies. Further, the main conclusions were based on similarity between maps, but similarity does not imply the absence of meaningful differences. In contrast, LNM provides evidence for meaningful differences using specificity testing. Exemplary analyses of 1090 lesion locations from 34 prior LNM studies do not support van den Heuvel’s concerns and confirm the lesion-deficit specificity of LNM. While we encourage further methodological investigation, the analyses of van den Heuvel et al. do not invalidate prior LNM findings or future applications.
Institutions: Northwestern University, Brigham and Women's Hospital, Harvard University, University Hospital Cologne, Boston Children's Hospital, University of Turku, Turku University Hospital, The University of Texas Rio Grande Valley, National Hospital for Neurology and Neurosurgery, UCL Queen Square Institute of Neurology, University College London, University of Oxford, University of Iowa
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Funders: Suomen Lääketieteen Säätiö, Once Upon A Time Foundation, BrainsWay, Deutsche Forschungsgemeinschaft, Päivikki ja Sakari Sohlbergin Säätiö, Signe ja Ane Gyllenbergin Säätiö, Turun Yliopisto, Turun Yliopistollinen Keskussairaala, Epilepsy Society, National Institutes of Health, Parkinsonfonden, National Institute of Mental Health, National Human Genome Research Institute, National Institute of Neurological Disorders and Stroke
Awards: Personalized circuit-based neuromodulation targets for depression, Targeted modulation of symptom-specific brain circuits with transcranial magnetic stimulation, VIPS: Vascular Effects of Infection in Pediatric Stroke, SFB 1270: ELektrisch Aktive ImplaNtatE – ELAINE, Identifying neuromodulation targets for pain in the human brain, SFB 1451: Schlüsselmechanismen normaler und krankheitsbedingt gestörter motorischer Kontrolle, Seizures and Children's Outcomes after Stroke (SCOUTS), A causal wiring diagram of transdiagnostic brain functions, Optimized methods for measuring brain excitability in depression, Investigating the neural mechanisms of repetitive brain stimulation with invasive and noninvasive electrophysiology in humans, UTRGV Center for Genome Research, Using Brain Lesions and Deep Brain Stimulation to Identify an Epilepsy Circuit, Understanding Heterogeneity Across PTSD, MDD and Anxiety By Leveraging Large-scale Multimodal Neuroimaging Datasets, Enhancing PALM with novel statistical methods, cloud integration, parallelization, and imaging standards, Toward Connectomic Deep Brain Stimulation in Obsessive Compulsive Disorder, Optimizing Neuromodulation Therapies for Epilepsy: Identifying the Right Patient, Right Place, and Right Time for Stimulation, BRAIN CONNECTS: The center for Large-scale Imaging of Neural Circuits (LINC), Using human brain connectivity to identify the causal neuroanatomical substrate of depression symptoms
OpenAlex ID: W7131679253