A popular technique for studying brain disorders, known as lesion network mapping (LNM), appears to have a fundamental limitation. This is the conclusion of neuroscientists from Vrije Universiteit Amsterdam and the University of Queensland (Australia) after an extensive analysis of more than 200 studies.
The findings raise important questions about how reliable this method is for distinguishing specific brain networks in neurological and psychiatric disorders. The critical study has been published in Nature Neuroscience
LNM is used worldwide to link brain lesions and other local brain changes visible on MRI scans to underlying brain networks. In this way, researchers hope to better understand which networks are involved in conditions such as depression, addiction, psychosis, and epilepsy, enabling more targeted treatments. Remarkably, however, many of these studies show almost identical brain networks, regardless of the disorder being investigated.
Standard map of functional connections in the brain
The team led by University Research Chair (URC) Professor of Computational Neuroscience Martijn van den Heuvel at the CNCR investigated how this could be the case. They reanalyzed data from multiple LNM studies and critically examined the method. Their analysis shows that LNM essentially relies repeatedly on the same standard map of connections in the brain. Because of this repeated “sampling,” diverse brain changes - whether derived from patients, imaging data, or even randomly generated- are consistently linked to the same general network patterns, without providing disease-specific information.
“The method projects all kinds of brain changes onto the same non-specific properties of the data source being used,” Van den Heuvel explains. As a result, highly similar networks emerge, even though differences between disorders are precisely what matter for scientific insight and clinical applications.
‘Applying the brakes’
This limitation has important implications. Understanding specific brain networks forms the basis for more precise diagnoses and new treatments, such as brain stimulation or personalized therapies, dozens of clinical trials of which are currently underway worldwide. National and international colleagues emphasize the importance of this study in de Volkskrant and argue that we need to “apply the brakes.”
At the same time, the research also offers perspective. “By exposing the shortcomings of LNM, we hope to contribute to the development of a new generation of network-mapping methods. These should be better grounded in fundamental principles and thus capable of identifying the biological networks underlying different brain disorders,” Van den Heuvel says.
The figure shows some examples of how the same networks are found in widely varying conditions.