Invited Symposium 2 - Advances in lesion methods: Mapping, plasticity, disconnectomics, and more

Invited Symposium 2: Sunday, March 30, 2025, 10:00 am – 12:00 pm EDT, Constitution Ballroom

Chair: Lesley Fellows¹; ¹McGill University
Presenters: Pedro Nascimento Alves, Chris Rorden, Erin Meier, Michel Thiebaut de Schotten

Studies of the effects of focal brain lesions on behaviour are at the foundation of cognitive neuroscience. Clinical case reports were pivotal in launching the study of the brain basis of many cognitive functions, with the symptoms of patients such as Leborgne, H.M., and Phineas Gage still serving as touchstones and sources of inspiration in our field. With the proliferation of new methods to study the healthy human brain in recent years, lesion research took something of a back seat in cognitive neuroscience. However, it continues to be a crucial source of causal evidence for brain-behavior relationships, complementing the correlational findings from other methods. Lesion studies are also natural bridges for the clinical translation of cognitive neuroscience insights. Human lesion research has not been resting on its inferential and translational laurels: Methodological and analytic innovations have improved how we define the effects of lesions, including considering both local and distant effects, and how lesion-induced dysfunction is mapped to component processes of behavior. Larger sample sizes and sophisticated statistical approaches have enhanced reliability and generalizability. This symposium will provide an overview of recent advances in lesion research methodologies, give examples of how lesion findings have supported or questioned current models of the neural substrates of cognition, and discuss how these methods can be best applied to enhance our understanding of the human brain and to use that understanding to improve health.

Presentations

Using Human Brain Lesions to Infer Function: Entering a New Era

Chris Rorden¹, Hans-Otto Karnath², Leonardo Bonilha¹; ¹University of South Carolina, ²University of Tübingen, Germany

Lesion mapping provides unique insights into the causal relationships between brain regions and cognitive functions, leveraging routine clinical imaging data to address critical questions about brain function and injury. Unlike other neuroimaging methods, lesion studies capitalize on vast existing datasets from routine care, enhancing generalizability and patient impact. Recent advances in imaging, machine learning, and network modeling have revolutionized this field, allowing for accurate prognosis, personalized treatment, and deeper understanding of brain resilience and recovery. However, lesion-based methods face challenges, including spatial biases from vascular architecture and limited data on infrequently injured regions. Innovative approaches like disconnectome analyses and complementary injury types (e.g., traumatic brain injury, tumors) mitigate these issues, while machine learning identifies synergistic predictors from diverse datasets. Clinical applications extend beyond neuroscience, improving stroke care, trial design, and preventative strategies. Future progress requires standardized behavioral metrics, longitudinal studies, and robust data-sharing frameworks. Advances in anonymization, data alignment, and federated learning address privacy concerns and enhance collaborative research. This new era integrates lesion-based tools with complementary methods, advancing both basic neuroscience and clinical care.

Evolution of lesion-behavior relationships over time: Evidence from acute to chronic stroke

Erin Meier^1,2, Argye Hillis²; ¹Northeastern University, ²Johns Hopkins University School of Medicine

The emergence and subsequent widespread application of lesion-symptom mapping (LSM) techniques has revolutionized scientific understanding of the neural architecture of complex cognitive processes. Unlike cross-sectional studies, longitudinal LSM elucidates how causal brain-behavior relationships evolve over time, providing insight into potential redundancy within cognitive networks. In stroke research, LSM in acute and chronic samples differs in its theoretical implications and methodological requirements. Lesion correlates of acute stroke impairments likely reflect critical processing nodes of the undamaged, neurotypical network whereas lesion findings unique to the chronic stroke stage likely reflect neural reorganization and recovery. Work from our group has demonstrated the importance of incorporating other markers of tissue dysfunction (e.g., hypoperfusion, white matter hyperintensities) into LSM models in different stroke recovery stages. In this talk, we will consolidate and review findings from over 20 years of work from our group regarding lesion correlates of language deficits in acute to chronic stroke in order to demonstrate the power of LSM and its implications for the neurobiology of language.

Mapping the effects of brain lesions on neurotransmitter circuits

Pedro Nascimento Alves¹, Justine Y Hansen²; ¹Universidade de Lisboa, Portugal, ²McGill University

The discovery of neurotransmitters reshaped our understanding of brain function. Distinctive patterns of neurotransmission frame determinant circuits for cognition and behavior. Stroke, as a predominant cause of brain pathology, triggers a cascade of cognitive and behavioral sequelae. The relationship between the neurotransmitter systems and deficits arising from stroke presents a promising avenue for exploration. Yet, the challenges of neurotransmitter circuits mapping in vivo have hampered this investigation. Recently, we combined normative nuclear medicine imaging data with tractography to develop a novel MRI white matter atlas of neurotransmitter circuits. We created a tool - the NeuroT-map - that estimates how stroke damages neurotransmitter systems and innovatively charts if the disruption was predominantly pre or postsynaptic, taking into account neurochemical diaschisis. We will show the main patterns of neurotransmitter circuit damage in stroke and discuss the potential of tailored neurotransmitter modulation treatments for stroke-associated cognitive dysfunction.

The emergent symptoms of the disconnected brain

Michel Thiebaut de Schotten^1,2, Anna Masleuvits², Chris Foulon², Lia Talozzi²; ¹Sorbonne Universities, Paris, ²CEA University of Bordeaux

Significant strides have been made in delineating the white matter architecture in the living human brain in the last two decades. These pathways have been identified as pivotal in supporting cognitive functions, with their variability closely associated with differences in cognitive performance, psychiatric conditions, and neurological manifestations. This underscores a hypothesis that brain functionality is not isolated within regions but emerges from the interaction facilitated by white matter connections. In our presentation, we will unveil cutting-edge methodologies developed recently in our lab – namely, the disconnectome and emuse – to explore these emergent properties. We will discuss their implications for understanding complex neuroscientific phenomena, such as consciousness and neuropsychological recovery post-stroke.