Publicación en la Revista Internacional de Neuropsychological de la sociedad

Journal of the International Neuropsychological Society (2013), 19, 1–12.

Copyright E INS. Published by Cambridge University Press, 2013.

doi:10.1017/S135561771300060X

1 Neuroanatomical Correlates of Executive Functions:

2 A Neuropsychological Approach Using the EXAMINER

3 Battery

4 Heather Robinson,1 Matthew Calamia,1 Jan Gla¨scher,2 Joel Bruss,3

AND Daniel Tranel1,3

5 1Department of Psychology, University of Iowa, Iowa City, Iowa

6 2Department for Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

7 3Department of Neurology, Division of Behavioral Neurology and Cognitive Neuroscience, University of Iowa College of Medicine,

8 Iowa City, Iowa

9 (RECEIVED January 15, 2013; FINAL REVISION May 4, 2013; ACCEPTED May 6, 2013)

10 Abstract

11 Executive functions (EF) encompass a variety of higher-order capacities such as judgment, planning, decision-making,

12 response monitoring, insight, and self-regulation. Measuring such abilities quantitatively and establishing their neural

13 correlates has proven to be challenging. Here, using a lesion-deficit approach, we report the neural correlates of a variety

14 of EF tests that were developed under the auspices of the NINDS-supported EXAMINER project (Kramer, 2011;

15 www.examiner.ucsf.edu). We administered a diverse set of EF tasks that tap three general domains—cognitive, social/

16 emotional, and insight—to 37 patients with focal lesions to the frontal lobes, and 25 patients with lesions outside the

17 frontal lobes. Using voxel-based lesion-symptom mapping (VLSM), we found that damage to the ventromedial prefrontal

18 cortex (vmPFC) was predominately associated with deficits in social/emotional aspects of EF, while damage to

19 dorsolateral prefrontal cortex (dlPFC) and anterior cingulate was predominately associated with deficits in cognitive

20 aspects of EF. Evidence for an important role of some non-frontal regions (e.g., the temporal poles) in some aspects of

21 EF was also found. The results provide further evidence for the neural basis of EF, and extend previous findings of the

22 dissociation between the roles of the ventromedial and dorsolateral prefrontal sectors in organizing, implementing, and

23 monitoring goal-directed behavior. (JINS, 2013, 19, 1–12) 24

25 Keywords: Insight, Self-monitoring, FrSBe, Lesion, Cognitive control, Empathy

26 INTRODUCTION

27 Executive functioning (EF) is a broad term encompassing

28 domains such as volition, planning and decision-making,

29 purposive action, self-regulation, and effective performance

30 (Lezak, Howieson, Bigler, & Tranel, 2012). Although a diverse

31 set of brain regions are involved in executive functioning, the

32 frontal lobes are considered to provide the principal neural

33 substrate (e.g., Stuss, 2011; Stuss & Knight, 2002). Within the

34 frontal lobes, the division between the dorsolateral prefrontal

35 cortex (dlPFC) and the ventromedial prefrontal cortex (vmPFC)

36 is critical in understanding two distinct types of abilities sub-

37 sumed under the term executive functioning: ‘‘metacognitive

38 executive functions’’ and ‘‘emotional/motivational executive

39 functions,’’ respectively (Ardila, 2008; Stuss, 2011).

Metacognitive executive functions are those which organize 40

and monitor goal-directed behavior. These functions include 41

abilities assessed by traditional clinical and laboratory measures 42

of executive functioning (e.g., planning, response inhibition, 43

working memory) (Ardila, 2008). Various structural models 44

of these metacognitive functions have been proposed in 45

the literature. For example, Latzman and Markon (2010) 46

identified a three factor structure (‘‘conceptual flexibility,’’ 47

‘‘monitoring,’’ ‘‘inhibition’’) for scores on the Delis-Kaplan 48

Executive Function System (D-KEFS). This structure is 49

similar to a three-factor model (‘‘shifting,’’ ‘‘updating,’’ 50

‘‘inhibition’’) found using a different set of executive 51

functioning measures (Miyake et al., 2000). 52

In a lesion study of popular neuropsychological measures 53

of these ‘‘metacognitive’’ types of executive functions 54

(e.g., Wisconsin Card Sorting Test, Controlled Oral Word 55

Association Test), a relationship between deficits in these 56

functions and damage to the dlPFC and anterior cingulate 57

was found (Gla¨scher et al., 2012). This is consistent with a 58

Correspondence and reprint requests to: Daniel Tranel, Department of

Neurology, University of Iowa Hospitals and Clinics, 200 Hawkins Drive,

Iowa City, Iowa 52242. E-mail: daniel-tranel@uiowa.edu

1

59 large body of literature that has suggested a relationship

60 between cognitive components of executive functioning and

61 the dlPFC and anterior cingulate (for reviews, see Lezak

62 et al., 2012; Stuss & Levine, 2002). Moreover, in a meta-

63 analysis of functional neuroimaging studies of cognitive

64 measures of executive functioning, the dlPFC and anterior

65 cingulate were found to be the ‘‘critical nodes’’ activated

66 in both healthy adults and patients with schizophrenia

67 (Minzenberg, Laird, Thelen, Carter, & Glahn, 2009).

68 Emotional and motivational executive functions involve

69 ‘‘coordinating cognition and emotion’’ (Ardila, 2008). These

70 functions are related to the vmPFC (Lezak et al., 2012; Stuss

71 et al., 2002). Although patients with vmPFC damage main-

72 tain their formal knowledge of social norms—that is, they can

73 ‘‘talk a good game’’ and give appropriate verbal responses to

74 social hypotheticals (e.g., Beer, John, Scabini, & Knight,

75 2006; Saver & Damasio 1991), they fail to process emotional

76 information normally, and as a consequence have impair-

77 ments in affective and social decision-making, that is,

78 implementing social knowledge in the real world, in real

79 time, and ‘‘on line’’ (Bechara, 2004; Beer et al., 2006). As a

80 result of vmPFC damage, patients experience significant

81 changes in emotional (e.g., blunted affect) and social (e.g.,

82 increases in inappropriate social behavior) aspects of per-

83

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