Prefrontal lobe structural integrity and trail making test, part B: converging findings from surface-based cortical thickness and voxel-based lesion symptom analyses

Abstract

Surface-based cortical thickness (CT) analyses are increasingly being used to investigate variations in brain morphology across the spectrum of brain health, from neurotypical to neuropathological. An outstanding question is whether individual differences in cortical morphology, such as regionally increased or decreased CT, are associated with domain-specific performance deficits in healthy adults. Since CT studies are correlational, they cannot establish causality between brain morphology and cognitive performance. A direct comparison with classic lesion methods is needed to determine whether the regional specificity of CT-cognition correlations is similar to that observed in patients with brain lesions. We address this question by comparing the neuroanatomical overlap of effects when 1) whole brain vertex-wise CT is tested as a correlate of performance variability on a commonly used neuropsychological test of executive function, Trailmaking Test Part B (TMT-B), in healthy adults and 2) voxel-based lesion-symptom mapping (VBLSM) is used to map lesion location to performance decrements on the same task in patients with frontal lobe lesions. We found that reduced performance on the TMT-B was associated with increased CT in bilateral prefrontal regions in healthy adults and that results spatially overlapped in the left dorsomedial prefrontal cortex with findings from the VBLSM analysis in patients with frontal brain lesions. Findings indicate that variations in the structural integrity of the left dorsomedial prefrontal lobe, ranging from individual CT differences in healthy adults to structural lesions in patients with neurological disorders, are associated with poor performance on the TMT-B. These converging results suggest that the left dorsomedial prefrontal region houses a critical region for the complex processing demands of TMT-B, which include visuomotor tracking, sequencing, and cognitive flexibility.

Cognitive performance in juvenile myoclonic epilepsy patients with specific endophenotypes

“…This result was maintained even after control for total and sedating drug daily doses, age at epilepsy onset, and seizure control. Trail Making Test B demands a complex processing that includes visuomotor coordination, sequencing, cognitive flexibility, and processing speed, and is sensitive to frontal lobe damage [50]. This particular JME group, in which more than one epileptic network seems to be involved in seizure generation as testified through specific reflex traits, also had the higher impairment in Trail Making Test B.…”

“…Trail Making Test B has been frequently used in neuropsychological research due to its reliability and sensitivity to executive dysfunction for patients with neurological disorders [50]. In a fMRI study, patients with frontal lesions showed the most consistent performance decrements in this neuropsychological test and had a more localized activation in left dorsomedial prefrontal cortex [50].…”

“…Trail Making Test B has been frequently used in neuropsychological research due to its reliability and sensitivity to executive dysfunction for patients with neurological disorders [50]. In a fMRI study, patients with frontal lesions showed the most consistent performance decrements in this neuropsychological test and had a more localized activation in left dorsomedial prefrontal cortex [50]. As a measure of functional deficit area of the epileptogenic zone, the present series confirms frontal dysfunction in JME [40,55,56] and associates this impairment with the presence of a more widespread epileptogenic network, as attested by the presence of praxis and photosensitivity in the same patients (group 4).…”

Mentalization deficit in bipolar patients during an acute depressive and manic episode: association with cognitive functions

“…A meta-analysis of structural neuroimaging studies showed that the performance on these tests is related to the volume of the prefrontal cortex, mainly the lateral and medial parts of it (Yuan and Raz 2014 ). Recent studies have also shown an association between the dorsomedial prefrontal cortex and TMT B performance (Miskin et al 2016 ) and between DLPFC and WCST (Boschin et al 2016 ). This may indicate that a DLPFC abnormality in bipolar patients plays a role for both mentalization deficits and cognitive disorders.…”

The role of left insula in executive set-switching: Lesion evidence from an acute stroke cohort

“…Another large-sample study of individuals with penetrating head injuries (N = 182) reported an association between regionally non-specific lesions within the left prefrontal cortex, anterior cingulate, insula, parietal and temporal areas and lower executive functioning, as evaluated by the Delis-Kaplan Executive Function System (D-KEFS) tests that included the TMT ( Barbey et al., 2012 ). Furthermore, damage to the left dorsomedial prefrontal cortex was associated with slower set-switching in a study of 27 frontal chronic brain-injured patients with heterogeneous aetiologies ( Miskin et al., 2016 ). Finally, lesions within the right dorsolateral prefrontal cortex predicted higher incidence of set-switching errors in a sample of 30 acute, right-hemispheric and predominantly frontal stroke patients ( Kopp et al., 2015 ).…”