The Trail Making Test (TMT) is an extensively used neuropsychological instrument for the assessment of set-switching ability across a wide range of neurological conditions. However, the exact nature of the cognitive processes and associated brain regions contributing to the performance on the TMT remains unclear. In this review, we first introduce the TMT by discussing its administration and scoring approaches. We then examine converging evidence and divergent findings concerning the brain regions related to TMT performance, as identified by lesion-symptom mapping studies conducted in brain-injured patients and functional magnetic resonance imaging studies conducted in healthy participants. After addressing factors that may account for the heterogeneity in the brain regions reported by these studies, we identify future research endeavours that may permit disentangling the different processes contributing to TMT performance and relating them to specific brain circuits.

Impairments in executive functions are common in stroke survivors, both in the acute and in the chronic phase. However, little is known about the underlying lesion neuroanatomy of these deficits. This study aimed to elucidate the pattern of brain damage underlying executive dysfunction in a large and acute stroke cohort. Executive set-switching deficits were evaluated by a shape-based analogue of the Trail Making Test (from the Oxford Cognitive Screen) in a consecutive sample of 144 stroke patients (age: 70 ± 15 years, examination: 5 ± 4 days post-stroke; brain imaging: 1.7 ± 2.9 days post-stroke). A voxelwise lesion-symptom mapping analysis was performed by combining executive set-switching accuracy scores with manually delineated lesions on computerized tomography or magnetic resonance imaging scans. The analysis showed that lesions within the left insular cortex and adjacent white matter predicted poorer executive set-switching. Further analyses confirmed that the lesion effect in the left insula survived correction for the low-level visuospatial and motor component processes of executive set-switching. In conclusion, the study provides lesion-based evidence for the role of the left insular cortex in flexible switching of attention. The findings are consistent with emergent models of insular function postulating the role of this region in regulatory aspects of goal-directed behaviour.