Executive deficits are related to the inferior frontal junction in early dementia

Abstract

Executive functions describe a wide variety of higher order cognitive processes that allow the flexible modification of thought and behaviour in response to changing cognitive or environmental contexts. Their impairment is common in neurodegenerative disorders. Executive deficits negatively affect everyday activities and hamper the ability to cope with other deficits, such as memory impairment in Alzheimer's disease or behavioural disorders in frontotemporal lobar degeneration. Our study aimed to characterize the neural correlates of executive functions by relating respective deficits to regional hypometabolism in early dementia. Executive functions were assessed with two classical tests, the Stroop and semantic fluency test and various subtests of the behavioural assessment of the dysexecutive syndrome test battery capturing essential aspects of executive abilities relevant to daily living. Impairments in executive functions were correlated with reductions in brain glucose utilization as measured by [(18)F]fluorodeoxyglucose positron emission tomography and analysed voxelwise using statistical parametric mapping in 54 subjects with early dementia, mainly Alzheimer's disease and frontotemporal lobar degeneration, and its prodromal stages: subjective and mild cognitive impairment. Although the analysis revealed task-specific frontoparietal networks, it consistently showed that hypometabolism in one region in the left lateral prefrontal cortex-the inferior frontal junction area-was related to performance in the various neuropsychological tests. This brain region has recently been related to the three component processes of cognitive control-working memory, task switching and inhibitory control. Group comparisons additionally showed hypometabolism in this area in Alzheimer's disease and frontotemporal lobar degeneration. Our study underlines the importance of the inferior frontal junction area for cognitive control in general and for executive deficits in early dementia.

Figure 1

Correlation between reductions in brain glucose utilization and executive dysfunctions—Stroop Test (Stroop), Category Fluency (Fluency) and subtest Action Program (Act. Pr.) of the BADS. Brain sections (location illustrated by crosshairs) visualize relevant neural clusters. Age as covariate. P < 0.001 uncorrected. Left is left. Colour scales represent t-values.

Figure 2

Correlation between reductions in brain glucose utilization and executive dysfunctions—Subtests Zoo Map (Zoo; Part 1 and 2) and Key Search (Key S.) of the BADS. Brain sections (location illustrated by crosshairs) visualize relevant neural clusters. Age as covariate. P < 0.001 uncorrected. Left is left. Colour scales represent t-values.

Figure 3

Conjunction analyses. Brain regions that showed consistently reduced glucose metabolism in association with executive deficits. (A) Overlap of t-maps of all five tests. Maximum is located in the vicinity of the inferior frontal junction area (i.e. in this region, t-values of all statistical tests are significant with voxelwise P < 0.001). Scale represents number of overlapping tests. (B) Minimum z-score for all five executive function tests which corresponds to a conjunction analysis in the sense of a logical ‘AND’. Maximum of the resulting map of z-values is again located in the vicinity of the inferior frontal junction. (C) Results of the meta-analysis of studies investigating Stroop (Str) and Switch (Sw) tasks with functional MRI transformed into the MNI space using the unified segmentation approach (Ov = overlap; Derrfuss et al., 2005). (D) Results of our previous study with exactly the same cohort investigating the neural correlates of behavioural disorders in dementia—correlation between reduced glucose metabolism and apathy (Ap), disinhibition (Dis) and eating disorders (Ea) (Schroeter et al., 2011).

Figure 4

Group comparison—brain regions that showed reduced glucose metabolism in Alzheimer's disease (AD, red) and frontotemporal lobar degeneration (FTLD, blue) in comparison with subjects with subjective cognitive impairment (SCI). Overlap (purple) includes the left inferior frontal junction area. Age as covariate, P < 0.001 uncorrected, extent threshold of 30 voxels. Left is left. Note that coordinates in MNI space are identical to Fig. 3.