From correlational approaches to meta-analytical symptom reading in individual patients: Bilateral lesions in the inferior frontal junction specifically cause dysexecutive syndrome

Abstract

Background: Executive functions describe a wide variety of higher order cognitive processes allowing the modification of thought and behavior in response to changing contexts. Recent comprehensive quantitative and systematic meta-analyses on functional imaging studies in healthy subjects identified the inferior frontal junction (IFJ), located at the junction of the inferior frontal sulcus and the inferior precentral sulcus, as essential for executive functions. Lesion studies in patients are necessary for confirmation of this finding.

Case presentation: We present, as a proof of concept, a 56 year old woman with bilateral ischemic lesions in the IFJ caused by multiple stroke-related brain infarcts in the bilateral territory of the middle cerebral artery. Comprehensive neuropsychological testing revealed specific deficits in executive functions, namely working memory, task switching, inhibitory control, interference resolution, fluency, and complex executive function tests focusing on action planning and problem solving abilities. Memory functions were within the normal range. Furthermore, we applied comprehensive meta-analyses to validate the importance of the IFJ for executive functions. (i) Lesions in the patient's brain in the IFJ coincide with regional activation in functional imaging studies for working memory, task switching, and the Stroop task. (ii) Lesions in the patient's IFJ should affect a frontoparietal network as shown with connectivity analyses. (iii) We introduce a new analysis tool - Meta-Analytical Reading of Symptoms (MARS) - that enables prediction of clinical symptoms from imaging data in individual patients.

Conclusions: Our study confirms the importance of the IFJ as the causal agent, in a frontoparietal network, for dysexecutive syndrome. As a lesion study, it goes beyond correlational imaging approaches. The new meta-analytical symptom reading approach can be applied in other patients and diseases. It has a high potential to foster individualized diagnosis and therapy in clinical settings in the framework of personalized medicine.

Keywords: BrainMap; Executive functions; Inferior frontal junction; Lesion study; Meta-analysis; Neurosynth; meta-Analytical symptom reading.