selective impairment of the conflict network in patients
TRANSCRIPT
Selective impairment of the conflict network in patients with frontal lesions
Von der Medizinischen Fakultät
der Rheinisch-Westfälischen Technischen Hochschule Aachen zur Erlangung des akademischen Grades
einer Doktorin der Medizin genehmigte Dissertation
vorgelegt von
Eva-Maria Meier
aus
Paderborn
Berichter: Herr Universitätsprofessor Dr.phil. Dipl.-Psych. Siegfried Gauggel Herr Universitätsprofessor Dr.rer.nat. Klaus Willmes-von Hinckeldey Tag der mündlichen Prüfung: 12. Juli 2011 Diese Dissertation ist auf den Internetseiten der Hochschulbibliothek online verfügbar.
brought to you by COREView metadata, citation and similar papers at core.ac.uk
provided by Publikationsserver der RWTH Aachen University
Table of contents
ABBREVIATIONS ..................................................................................... 1
1. INTRODUCTION ................................................................................... 2
2. METHODS............................................................................................. 6
2.1 Participants.................................................................................................................. 6
2.2 Background neuropsychological assessment ........................................................ 7
2.3. Attention Network Test (ANT)................................................................................... 8
2.4. Procedure ................................................................................................................. 10
2.5. Lesion analysis ........................................................................................................ 11
2.6 Statistical analysis.................................................................................................... 11
3. RESULTS............................................................................................ 13
3.1 Background neuropsychological assessment ...................................................... 13
3.2 Performance in the ANT ........................................................................................... 13
4. DISCUSSION ...................................................................................... 18
5. SUMMARIES....................................................................................... 22
5.1. English summary ..................................................................................................... 22
5.2. Deutsche Zusammenfassung ................................................................................. 23
6. REFERENCES .................................................................................... 24
7. APPENDIX .......................................................................................... 31
7.1. List of tables ............................................................................................................. 31
7.2. List of figures ........................................................................................................... 32
7.3. Supplementary material .......................................................................................... 33
8. ERKLÄRUNG § 5 ABS. 1 ZUR DATENAUFBEWAHRUNG .............. 43
9. CURRICULUM VITAE......................................................................... 45
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
1
Abbreviations
ACC anterior cingulate cortex
ADHD attention-deficit/hyperactivity disorder
ANOVA analysis of variance
ANT Attention Network Test
bi bilateral
CG control group
CT computer tomography
DLPFC dorsolateral prefrontal cortex
ES effect size
ESC elementary school
FG frontal group
fMRI functional magnetic resonance imaging
GS grammar school
l left
LPS Leistungs-Prüf-System
MRI magnetic resonance imaging
m mean
n number
NFG non-frontal group
r right
RAE relative alerting effect
RCE relative conflict effect
ROE relative orienting effect
RT reaction time
SD standard deviation
SGS secondary general school
SMS secondary modern school
TMS transcranial magnetic stimulation
TMT Trail Making Test
VLMT Verbaler Lern- und Merkfähigkeitstes
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
2
1. Introduction
Executive functions play an important role in daily living, due to the fact
that they enable us to handle situations in which routine or automatic
processes are incommensurate. That is why patients with lesions in
responsible brain areas are impaired in performing several actions as
planning, decision making or attentional control. Because of the enormous
importance of executive functions, there exist many theories about this
issue (for example Posner & Rothbart, 1998; Norman & Shallice, 1986;
Berger & Posner, 2000).
One important aspect of executive control is monitoring and resolving
conflict. Miller & Cohen (2001) illustrate the occurrence of conflict as a
situation in which two trains want to cross tracks at the same time. In daily
life conflict occurs when competing responses or information are present
(Durston et al., 2003), for example the doorbell rings while someone is
talking on the phone. Ullsperger & von Cramon (2004) defined the term
“pre-response conflict” which arises when more than one response
tendencies induced by the same goal are activated simultaneously and
when these response tendencies are in conflict. Especially during
perceptual representation, stimulus categorization, response selection and
task representation a high degree of response conflict can be triggered
(Botvinick et al., 2004). Response conflict manifests itself in uncertainness
in handling such situations and an increased incidence of errors. Only
task-appropriate stimuli and responses have to be allocated and
distracting stimuli and thoughts have to be ignored. For this reason there is
a need for “cognitive control” which is described as the ability to generate,
maintain and adjust sets of goal-directed processing strategies (Egner,
2008).
Botvinick et al. (1999) established the conflict monitoring hypothesis with
the following considerations:
1) Specific subsystems in the human brain monitor the occurrence of
conflict in information processing.
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
3
2) The occurrence of conflict triggers strategic adjustments in cognitive
control, which serve to prevent conflict in subsequent performance.
3) Conflict monitoring might represent one aspect of a more general
monitoring function, which detects internal states signalling a need
to intensify or redirect attention or control.
These cognitive control processes have top-down influences on other
brain areas involved in motor and sensory converting, whereas simple and
automatic behaviour rely on stereotyped reactions and bottom-up
processing (guided activation theory by Miller & Cohen, 2001).
The investigation of responsible brain areas for accomplishing these
cognitive processes has grown in popularity over the last years. Studies
using different methods which will be subsequently explained in greater
detail indicate that especially frontal brain areas are important for resolving
response conflict. Several functional magnetic resonance imaging (fMRI)
studies in healthy subjects have implicated a network of brain areas which
are activated during flanker task performance: the anterior cingulate cortex
(ACC; Botvinick et al., 1999; Bunge et al., 2002; Casey et al., 2000;
Durston et al., 2003; Fan et al., 2003, 2005, 2007, 2008; Hazeltine et al.,
2003; Lau et al., 2006; Luks et al., 2007; McNab et al., 2008; Ochsner et
al., 2009; van Veen et al., 2001; Wager et al., 2005), the dorsolateral
prefrontal cortex (DLPFC; Casey et al., 2000; Durston et al. 2003; Fan et
al., 2007; Luks et al., 2007; van Veen et al., 2001) and parietal regions
(Bunge et al., 2002; Casey et al., 2000; Durston et al., 2003; Fan et al.,
2007; Hazeltine et al., 2000; Luks et al., 2007; van Veen et al. 2001;
Wager et al., 2005; Wang et al., 2010). Table 4 in the appendix gives a
detailed review over all of these studies.
Similar regions were also activated in studies using the Stroop task, which
is a further tool for measuring conflict (Barch et al., 2001; Carter et al.,
2000; Haupt et al., 2009; Kerns et al., 2004; MacDonald et al., 2000;
Roberts et al., 2008; Zysset et al., 2001). Studies of Stroop task using
fMRI in healthy controls are listed in table 5 in the appendix.
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
4
Figure 1. Frontal brain areas play an important role in handling with the
occurrence of conflict: frontal lobe and anterior cingulate cortex
(BrainVoyager Brain Tutor, Version 2.0).
Another way to localize relevant brain areas is transcranial magnetic
stimulation (TMS). Using TMS, Taylor et al. (2007) simulated a lesion in
the dorsal medial frontal cortex in 16 subjects during performance of the
flanker task. Their results indicate that dorsal medial frontal cortex
resolves conflict by exerting top-down control.
Given that many neuroimaging studies already addressed the allocation of
these processes, lesion studies complement their results by indicating if
different brain regions are essential for resolving response conflict. Only
few studies have so far investigated the performance of brain-damaged
patients in the flanker task (Beck et al., 2008; Rafal et al., 1996; Snow &
Mattingley, 2006), the Stroop task (Baird et al., 2006; Cohen et al., 1999;
Fellows & Farah, 2005; Stuss et al., 2001; Swick & Turken, 2002; Swick &
Jovanovic, 2002; Vendrell et al., 1995) and the Simon task (di Pelligrino et
al., 2007), most of them demonstrating that lesions in the ACC are
associated with impaired performance. In comparison to this study neither
used the ANT to measure response conflict, nor did they compare the
results of the patients with those of a healthy control group. Further studies
with neurological and psychiatric patients revealed that Chorea Huntington
(Beste et al., 2008), Morbus Parkinson (Wylie et al., 2005), attention-
deficit/hyperactivity disorder (ADHD; Bush et al., 1999), schizophrenia
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
5
(Carter et al., 1997) and depression (Holmes et al., 2008) are associated
with an impairment in monitoring and resolving response conflict.
As mentioned above, in many neuropsychological studies response
conflict was triggered within different paradigms: flanker task (Bunge et al.,
2002), Stroop task (Carter et al., 2000), Simon task (Wühr et al., 2008)
and go/no-go paradigm (Casey et al., 1997). In the present study the
Attention Network Test (ANT) developed by Fan and colleagues was used,
to operationalize a conflict situation. The ANT is a combination of the
flanker task (Eriksen & Eriksen, 1974) and the cued reaction time
paradigm(Posner, 1980) and determines the three attentional networks:
alerting, orienting and executive attention. The ANT was used amongst
others to investigate the independence and heritability of the three
different attentional networks (Fan et al., 2001; 2002), in functional
magnetic resonance imaging (fMRI) studies with children and adults
(Konrad et al., 2005; Fan et al., 2003, 2005, 2007, 2008) and in patients
with schizophrenia (Gooding et al., 2006) or borderline personality disorder
(Posner et al., 2002). Up to now only Beck et al. (2008) applied the ANT in
neurological patients with stroke or traumatic brain injury indicating the
clinical usefulness of this test. Most notably mean reaction time was the
best predictor for attention deficits. However, they neither compared the
results of the patients with a group of healthy controls, nor did they
separate the patients on the basis of their lesion localization into different
groups.
On account of this, the present study deals with performance on the ANT
in neurological patients with frontal and non-frontal brain lesions, turning
attention to the conflict effect. The hypothesis of this study is that patients
with frontal brain areas show a selective impairment in the conflict effect of
the ANT and normal performance in orienting, alerting and the background
neuropsychological assessment as compared to patients with non-frontal
brain lesions.
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
6
2. Methods
2.1 Participants
The 22 neurological patients were a consecutive sample and were
selected during their inpatient stay in the neurological department of the
university hospital of the RWTH Aachen according to the location and
etiology of their brain lesion. Only patients with ischaemic stroke or tumor
were asked to participate in the study and were tested in the subacute
state. Exclusion criteria were aphasia with comprehension difficulties,
massive intellectual deficits, degenerative neurological disorders, visual
disorders, neglect and German not as first language. On the basis of
neuroradiological findings in computer tomography (CT) or magnetic
resonance imaging (MRI) the patients were divided into two groups: the
frontal group (FG) containing 11 patients with lesion located predominantly
in the frontal lobe and the non-frontal group (NFG) containing 11 patients
with lesion outside the frontal lobe. The two groups did not differ as to age.
Details of patient characteristics are summarized in table 2. For a review of
the lesion localizations of the patients see table 6 in the appendix.
Additionally, 11 age and education matched healthy controls were tested
to compare their performance with those of the patients. All participants
reported normal or corrected to normal vision. Written informed consent
was obtained from all participants after complete description of the study
before the session. Participants participated voluntarily and received no
payment for study participation. The project was approved by the local
Ethics Committee of the Medical Faculty of the RWTH Aachen.
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
7
Table 1. Demographic and clinical data of patients with frontal lesions
(FG), patients with non-frontal lesions (NFG) and healthy controls (CG).
FG NFG CG
(n=9) (n=11) (n=11)
Sex: (male/female) 4/5 8/3 5/6
Age (M, SD) 56 (16) 57 (17) 58 (14)
Graduation (ESC/SGS/SMS/GS)1 3/1/3/2 1/4/2/4 2/2/3/4
Handedness premorbid (r/l/bi)2** 9/0/0 9/2/0
Handedness at testing date (r/l/bi) 8/1/0 9/2/0 11/0/0
Etiology (stroke/tumor) 7/2 11/0
Days since onset (M, SD) 11.7 (5.3) 7.2 (2.9)
1 ESC = elementary school, SGS = secondary general school, SMS = secondary modern school, GS = grammar school; 2 r = right, l = left, bi = bilateral
2.2 Background neuropsychological assessment
To examine whether the participants showed comparable performance in
other cognitive functions, three different neuropsychological tests were
used:
VLMT (Verbaler Lern- und Merkfähigkeitstest, Auditory Verbal Learning
Test) by Helmstaedter, Lendt & Lux, 2001
The VLMT is a German version of the Auditory Verbal Learning Test and
measures verbal learning and memory. A learning list of 15 words is read
out to the patient in five successive trials, each one of them is followed by
a free recall, and after the fifth trial an interference list is read which also
has to be recalled. Finally a free recall of the learning list is accomplished.
The following specific values were engaged: sum of reproduced correct
words in trial 1 to trial 5 (learning efficiency), difference of named correct
words between trial 6 and trial 5 (performance of demand), false positive
words, number of perseverations and named words that belong to the
other list of words. Results are reported in scores of counted words.
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
8
TMT (Trail Making Test) by Reitan, 1955
The TMT consists of 2 different parts: part A analyses speed of information
processing whereas part B investigates cognitive flexibility. While in part A
the participant’s task is to connect numbers from 1 to 25 on a paper in
ascending order (TMT-A), in part B the 25 numbers and letters he has to
connect are in alternating order (TMT-B). Both tasks were timed by the
tester. Results are reported in ms.
LPS (Leistungs-Prüf-System, Achievement Measure System) by Horn,
1983: Subtest 4
The LPS (Achievement Measure System) tests abstract logical thinking
and reasoning respectively. Subtest 4 implies 40 items containing eight
digits and letters. The elements of each line are sorted according to
different rules. Within eight minutes the participant has to identify one
element in each line, which does not fit the rule. Results are reported in T-
values.
2.3. Attention Network Test (ANT)
The Attention Network Test (ANT), a choice reaction time task, was
originally developed by Jin Fan and colleagues (Sackler Institute, Cornell
University New York) and represents a combination of the cued reaction
time (Posner et al., 1980) and the flanker task (Eriksen & Eriksen, 1974).
We used Version 1.3.0 modified by Siegfried Gauggel and Maren Böcker
(Institute of Medical Psychology and Medical Sociology, RWTH Aachen) in
which four cue conditions (no cue, center cue, double cue, spatial cue, see
Figure 3) and three target conditions (congruent, incongruent, neutral, see
Figure 2) are integrated to investigate the efficacy of the following three
attentional networks: orienting, alertness and executive control. This study
concentrates on the executive control system which is operationalized
within the flanker paradigm. The stimuli consist of a row of 5 horizontal
black arrows. However, the participants are instructed to respond only to
the central one (target). Depending on the arrows direction they have to
press the left or the right button with the instruction to respond as fast and
as accurate as possible. The subjects are guided to look steadily at a
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
9
fixation cross in the middle of the computer screen, which is presented
before the arrows appear. In order to integrate a conflict condition, the
target is flanked by two arrows on each side, pointing to the same direction
(congruent condition) or the opposite direction (incongruent condition) of
the target. In a neutral condition the flankers consist of four lines without
information of direction (Figure 2). The difference between mean reaction
time (RT) of the incongruent and the congruent condition represents the
conflict effect.
Figure 2. Target conditions of the ANT.
The alertness component is introduced by the double cue condition, where
two stars, positioned above and below the fixation cross, precede the
stimuli. These cues do not give the subjects any information of direction,
but they tell the subject that the stimuli will immediately be presented. The
difference between no cue and double cue condition represents the
alerting effect (see Figure 3).
In the orienting condition a spatial cue gives the information where the
target will appear. Therefore a star is presented above or below the
fixation cross according to the location of the target. In order to introduce a
control condition, a center cue is released at the position of the fixation
cross. The orienting effect is estimated by the difference between the RT
of the center cue and the spatial cue condition.
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
10
Figure 3. Cue conditions of the ANT.
In Figure 3 the course of the ANT is presented. In each trial a fixation
cross appears until a cue condition is presented a variable time later (F1 =
400 - 1600 ms). After 100 ms the cue disappears and 400 ms (F2) later
the target stimuli appear as long as the participant responds with a button
press, but for no longer than 1700 ms. Having responded, the fixation
cross reappears for a variable duration (F3 = 3500 ms - RT – F1 ms).
Figure 4. Schema of the ANT.
2.4. Procedure
Participants were tested in a separate test room or their sickroom,
depending on their condition. First they performed the ANT, approximately
50 cm in front of a laptop. The test consisted of an instruction, a practice
block with 24 trials and three test blocks, each containing 96 trials. All trials
were randomized and each test block lasted 5 minutes, so that the entire
test took approximately 20 minutes. Afterwards the subjects received
feedback on their performance, which included the conflict, orienting and
alerting effect (in ms), mean RT (in ms) and accuracy (in percent).
Subsequently they accomplished the VLMT, LPS and TMT and also
obtained the results of these tests. Finally, in order to get more information
about the subject’s background, they filled out a demographic
questionnaire.
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
11
2.5. Lesion analysis
Available brain images of the patients were collected, preferably magnetic
resonance imaging (MRI). Computer tomography images were only used
in case of no MRI picture. Identifiable lesions were marked for each patient
in MRIcron (Rorden et al. 2007; for download see
http://www.sph.sc.edu/comd/rorden/mricron/). On the basis of these
pictures lesion localizations were determined (see Appendix table 6). The
method is demonstrated exemplary in figure 5.
Figure 5. In MRIcron marked lesion.
2.6 Statistical analysis
Behavioural data
For the statistical analysis the SPSS-Program Version 15 was used. First
all data were screened for deviation from normality, outliers and
homogeneity of variance. In a next step all dependent variables underwent
analyses of variance (ANOVA). In doing so, the three different groups
(frontal group, non-frontal group, healthy controls) were first compared
with respond to their performance in the background neuropsychological
assessment in order to reveal potential performance differences. For the
ANT, the standard parameters were compared between the three groups:
mean RT, mean accuracy, conflict effect, alerting effect and orienting
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
12
effect. Beside the absolute effects of the latter three dependent variables,
the relative effects were also compared, due to the fact that they account
for general differences of speed. The relative effects were computed by
means of the following formulas:
1) Conflict effect: Conflict effect * 100 / Median RTincongruent
2) Alerting effect: Alerting effect * 100 / Median RTno cue
3) Orienting effect: Orienting effect * 100 / Median RTcentral cue
They state the percental variance oriented on the baseline. Additionally,
effect sizes were calculated for the ANT parameters as effect sizes are
sample size independent and allow an estimation of the magnitude of the
difference between the investigated groups.
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
13
3. Results
3.1 Background neuropsychological assessment
One patient of the frontal group was not considered for the statistical
analysis of the TMT part A because his mean reaction time differed over
three standard deviations from the others so that he produced great
intergroup-differences.
Results of the background neuropsychological assessment are presented
in table 2.
Table 2. Neuropsychological data of patients with frontal lesions (FG),
patients with non-frontal lesions (NFG) and controls (CG).
FG NFG CG p F (k-1, n-k)
(M, SD, n) (M, SD, n) (M, SD, n)
VLMT Dg 1-5 42 (17) 8 42 (10) 10 45 (12) 11 0.76 0.3 (2, 26)
VLMT Dg 5 – 6 1 (2) 8 2 (2) 10 2 (2) 11 0.41 0.9 (2, 26)
VLMT FP 2 (5) 8 2 (2) 10 1 (3) 11 0.73 0.5 (2, 26)
VLMT P 4 (2) 8 3 (4) 10 4 (4) 11 0.90 0.1 (2, 26)
VLMT In 0.5 (0.6) 8 0.2 (0.4) 10 0.1 (0.3) 11 0.22 1.6 (2, 26)
TMT Part A (ms) 46 (28) 6 35 (11) 9 28 (8) 11 0.09 2.7 (2, 23)
TMT Part B (ms) 92 (61) 7 98 (46) 9 64 (30) 11 0.22 1.6 (2, 24)
LPS (T-score) 53 (11) 7 45 (11) 10 56 (9) 5 0.14 2.2 (2, 19)
VLMT = Verbal Learning and Memory Test, TMT = Trail Making Test, LPS = Achievement Measure System
No significant differences were found in the Verbal Learning and Memory
Test (VLMT), the Trail Making Test (TMT) and the Achievement Measure
System (LPS).
3.2 Performance in the ANT
Two patients of the frontal group were not considered for further analysis
in order to not distort the results. One of them was an outlier in the
accuracy, he differed over ten standard deviations from the others. The
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
14
test-results of the other one could not be utilized by the ANT for calculating
the variables, due to the fact that his reaction times were longer than
1700ms. Results of the ANT are presented in table 3 and in figures 6 to
10.
Table 3. Results of the ANT of patients with frontal lesions (FG), patients
with non-frontal lesions (NFG) and controls (CG).
FG (n=9) NFG (n=11) CG (n=11) p F (k-1, n-k)
(M, SD) (M, SD) (M, SD)
Mean RT (ms) 660 (152) 673 (99) 560 (73) 0.05 3.47 (2, 28)
Accuracy (%) 96.7 (4.4) 96.9 (3.4) 98.6 (0.8) 0.31 1.22 (2, 28)
Conflict e. (ms) 113 (50) 91 (39) 57 (26) 0.01 5.47 (2, 28)
RCE (%) 14.9 (3.7) 12.5 (4.9) 9.4 (4.1) 0.03 4.17 (2, 28)
Alerting e. (ms) 31 (32) 39 (20) 25 (13) 0.35 1.09 (2, 28)
RAE (%) 4.6 (4.1) 5.4 (2.3) 4.4 (2.4) 0.71 0.34 (2, 28)
Orienting e. (ms) 28 (32) 22 (28) 32 (18) 0.68 0.40 (2, 28)
ROE (%) 4.7 (4.6) 3.3 (4.0) 5.6 (3.0) 0.42 0.90 (2, 28)
RT = reaction time, e. = effect, RCE = relative conflict effect, RAE = relative
alerting effect, ROE = relative orienting effect
The oneway ANOVA showed significant differences between the three
groups in mean reaction time (F (2, 28) = 3.47, p = 0.05), the conflict effect
(F (2, 28) = 5.47, p = 0.01) and the relative conflict effect (F (2, 28) = 4.17,
p = 0.03). In accuracy (F (2, 28) = 1.22, p = 0.31), alerting effect (F (2, 28)
= 1.09, p = 0.35), relative alerting effect (F (2, 28) = 0.34, p = 0.71),
orienting effect (F (2, 28) = 0.40, p = 0.68) and relative orienting effect (F
(2, 28) = 0.90, p = 0.42) there were no significant differences between the
three groups.
Effect sizes (ES) for conflict effect (FG - NFG = 0.50, FG – CG = 1.46,
NFG – CG = 1.04) and relative conflict effect (FG – NFG = 0.54, FG – CG
= 1.40, NFG – CG = 0.68) showed a difference between frontal group and
non-frontal group of medium size and a great difference between patients
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
15
and controls indicating the greatest problems in resolving conflict in the
patients with frontal brain lesions. The large effect size for conflict effect
between the non-frontal group and the control group should be seen in
context with the general slowing of patients in mean reaction time. This is
reflected in the medium effect size for relative conflict effect between the
non-frontal group and the control group (NFG – CG = 0.69) and the great
difference between frontal group and control group (FG – CG = 1.59).
There were only small effects for mean reaction time and accuracy
between the patient groups, but as mentioned above obvious differences
between patients and control group indicating slower reaction times for the
patient groups (FG – CG = 0.88, NFG – CG = 1.30). Concerning the
accuracy, effect sizes of medium size were found for the differences
between the patients groups and the control group with the healthy
controls reacting more accurately than the patients (FG – CG = -0.61,
NFG – CG = -0.70). Alerting effect, relative alerting effect, orienting effect
and relative alerting effect showed only small effect sizes between the
patient groups and between patients and controls (see figures 6 to 10).
0
100
200
300
400
500
600
700
800
900
FG NFG CG
Indication
Mea
nre
acti
on
tim
e (m
s)
0
100
200
300
400
500
600
700
800
900
FG NFG CG
Indication
Mea
nre
acti
on
tim
e (m
s)
Figure 6. Mean reaction time of patients with frontal lesions (FG), patients
with non-frontal lesions (NFG) and controls (CG).
ES = 1.30
ES = 0.88
ES = -0.10
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
16
86
88
90
92
94
96
98
100
102
FG NFG CG
Indication
Ac
cu
racy
(%)
86
88
90
92
94
96
98
100
102
FG NFG CG
Indication
Ac
cu
racy
(%)
Figure 7. Accuracy of patients with frontal lesions (FG), patients with non-
frontal lesions (NFG) and controls (CG).
0
20
40
60
80
100
120
140
160
180
FG NFG CG
Indication
Co
nfl
ict
eff
ec
t(m
s)
0
20
40
60
80
100
120
140
160
180
FG NFG CG
Indication
Co
nfl
ict
eff
ec
t(m
s)
Figure 8. Conflict effect of patients with frontal lesions (FG), patients with
non-frontal lesions (NFG) and controls (CG).
ES = -0.70
ES = -0.65
ES = -0.05
ES = 1.04
ES = 1.46
ES = 0.50
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
17
-20
0
20
40
60
80
100
120
140
160
180
FG NFG CG
Indication
Ale
rtin
gef
fect
(ms)
-20
0
20
40
60
80
100
120
140
160
180
FG NFG CG
Indication
Ale
rtin
gef
fect
(ms)
Figure 9. Alerting effect of patients with frontal lesions (FG), patients with
non-frontal lesions (NFG) and controls (CG).
-20
0
20
40
60
80
100
120
140
160
180
FG NFG CG
Indication
Ori
en
tin
ge
ffec
t(m
s)
-20
0
20
40
60
80
100
120
140
160
180
FG NFG CG
Indication
Ori
en
tin
ge
ffec
t(m
s)
Figure 10. Orienting effect of patients with frontal lesions (FG), patients
with non-frontal lesions (NFG) and controls (CG).
ES = 0.83
ES = -0.31
ES = 0.26
ES = -0.42
ES = -0.14
ES = 0.21
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
18
4. Discussion
The aim of the present study was to investigate whether neurological patients
with lesions in frontal brain areas show impairment in detecting and resolving
conflict in comparison to patients with lesions in other brain areas and
healthy controls. The three groups performed the ANT and further
neuropsychological tests to distinguish if other cognitive control functions are
also affected. Given that many neuroimaging studies already identified
certain frontal brain areas that are involved in the detection and resolution of
conflict, this study also gives an answer to the question if these brain regions
are actually essential for this executive function.
Summarizing the most important results there are no significant differences in
the background neuropsychological assessment between the frontal group,
the non-frontal group and the control group. Relating to the ANT, there were
no appreciable differences comparing the frontal group with the non-frontal
group except for the conflict effect which argues for a strong dissociation.
The fact that patients were generally slower and less accurate in contrast to
healthy controls indicates a deficit in speed of information processing of brain
injured patients. This effect of general slowing in neurological patients was
found in other neuropsychological studies as well (Hochstenbach et al., 1998;
Ponsford et al., 1992; Zahn et al., 1999, Beck et al., 2008). Only Beck et al.
(2008) investigated the ANT performance of neurological patients with stroke
or traumatic brain injury, but they did not compare the results with those of a
healthy control group. Their patients showed longer mean reaction times than
our patient groups and our control group (M = 703 ms, SD = 169 ms). The
results of accuracy are similar with those of both patient groups, the patients
were less accurate than our control group (M = 97%, SD = 3%).
Investigating the responsible brain areas for resolving conflict, several
neuroimaging studies using the ANT (Fan et al., 2003, 2005, 2007, 2008),
other flanker tasks (Botvinick et al., 1999; Bunge et al., 2002; Casey et al.,
2000; Durston et al., 2003; Hazeltine et al., 2000, 2003; Lau et al., 2005;
Luks et al., 2007; McNab et al., 2008; Ochsner et al., 2009; van Veen et al.,
2001; Wager et al., 2005; Wang et al., 2009) and the Stroop task (Barch et
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
19
al., 2001; Carter et al., 2000; Haupt et al., 2009; Kerns et al., 2004;
MacDonald et al., 2000; Roberts et al., 2008; Zysset et al., 2001)
demonstrated that frontal brain areas like DLPFC and ACC were activated
during response conflict. However, imaging studies can not answer the
question whether these brain areas are essential.
Therefore lesion studies are very important in further research simply
because they have the possibility to complement the results of neuroimaging
studies by indicating that certain brain areas are necessary for performing a
task. Until now only few studies engage in the performance of flanker task in
brain damaged patients, and some of the results are consistent with our
findings (Rafal et al., 1996; Snow & Mattingley, 2006). Rafal et al. (1996)
compared the performance of a flanker task of patients with lesions involving
inferior lateral prefrontal cortex with those of neurological control patients.
Their lesion patients also showed longer reaction times for incompatible trials
indicating a deficit in response channel activation. Snow and Mattingley
(2006) tested patients with lesions in the right hemisphere not differentiating
between frontal and non-frontal regions. In comparison to a healthy control
group, the patients showed longer mean reaction times and longer reaction
times for incompatible flankers. This is consistent with our conclusion of
generally slowing in neurological patients. In addition to lesion studies TMS
was used during flanker tasks to verify the necessity of frontal brain regions
in response conflict. Taylor et al. (2007) applied TMS to left dorsal medial
frontal cortex demonstrating that this area modulates primary motor cortical
activity during conflict. In summary, neuroimaging and lesions studies
underline the hypothesis that frontal brain areas play an important role in
monitoring and resolving conflict.
Due to the fact that the present study was a clinical study, several
methodological limitations were given. Only a small number of patients could
participate in the study because most of the neurological patients did not
conform to the selection criteria. Due to this circumstance, the patient group
was very heterogeneous with respect to age and affected hemisphere, they
also showed different lesion localizations. Furthermore, some of the patients
with frontal lesions showed additional lesions in other brain areas, with the
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
20
most affected part allocated in the frontal lobe. With regard to the
neuroradiological data some patients got an MRI scan during their stay in the
neurological clinic, while others only got a CT. On account of these limitations
further lesion studies should emply a larger and more homogeneous group of
patients with identical neuroradiological image technique and lesions
allocated in those brain areas which are associated with the determined
function. Bates et al. (2003) developed a new method called ´Voxel-based
lesion-symptom mapping´ (VLSM). As in functional neuroimaging studies, the
relationship between tissue damage and behaviour is investigated on a
voxel-by-voxel basis. The outcome of this is continuous behavioural and
lesion information without any loss of information. For this method a greater
sample size of patients is very important.
Neuroimaging studies using time-resolved fMRI (Richter et al., 1999) or TMS
could help to decide between two prominent theories. According to the
conflict monitoring hypothesis (Botvinick et al., 1999), the ACC monitors the
occurrence of conflict between two competing responses and triggers
strategic adjustments in cognitive control to the DLPFC. The DLPFC then
has the executive function to resolve the conflict situation by exerting top-
down influences to other brain regions involved in sensory and motor
processing (Miller & Cohen, 2001). One of these brain areas is located in the
parietal cortex which is thought to be involved in activating appropriate motor
responses (Bunge et al., 2002). In contrast, the selection for action
hypothesis of Posner & diGirolamo (1998) suggests that the ACC and other
midfrontal areas are responsible for top-down attentional influences and
therefore for resolving conflict. The results of this study cannot disprove any
of these hypotheses. They do, however, underline that frontal brain areas are
a necessary part of the conflict network.
In conclusion, patients with lesions in frontal brain areas showed in
comparison to patients with non-frontal brain lesions and healthy controls a
significantly larger conflict effect in the ANT and normal performance in other
functions of cognitive functions. This dissociation is consistent with previous
findings in other lesion studies and several neuroimaging studies. The
controversially disputed function of ACC in response conflict (conflict
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
21
monitoring hypothesis by Botvinick et al., 1999 versus the selection for action
hypothesis of Posner & diGirolamo, 1998) can neither be verified nor can it
be disproved. However, we can deduce from the results that a frontal brain
network is necessary for the executive function of monitoring and resolving
conflict. Further studies with larger sample size and methods like VLSM or
time-resolved fMRI have to distinguish in particular which brain areas are
responsible for the specific process units during response competition.
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
22
5. Summaries
5.1. English summary
Many neuroimaging studies investigated the role of frontal brain areas in
monitoring and resolving conflict, but until now there exist only few lesion
studies. In order to reassess the necessity of frontal brain areas for
accomplishing this executive function, we used a lesion study design to
compare 11 neurological patients with frontal brain lesions with 11 patients
with non-frontal brain lesions and 11 healthy controls with regard to their
performance in the Attention Network Test (ANT), especially in the conflict
effect. Besides a general slowing effect in both patient groups indicated by a
slower overall mean reaction time as compared to the healthy controls, a
significant difference between the three groups was given for the conflict
effect and the relative conflict effect. In doing so medium effect sizes were
found for the conflict effect and relative conflict effect between the frontal
group and non-frontal group and great effect sizes between patients and
healthy controls indicating greater difficulties of resolving conflict in the
patients with frontal brain lesions. As no differences were found for other
cognitive functions, these results indicate that patients with frontal lesions are
selectively impaired in the conflict effect of the ANT. This dissociation
complements the results of functional magnetic resonance imaging (fMRI)
studies (Fan et al., 2002, 2005, 2007, 2008) proving the necessity of these
brain areas for this executive function.
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
23
5.2. Deutsche Zusammenfassung
Viele bildgebende Studien haben sich in den letzten Jahren mit dem
Zusammenhang zwischen frontalen Hirnarealen und dem Erkennen und
Lösen einer Konfliktsituation beschäftigt, jedoch gibt es bisher kaum
Läsionsstudien, die dieses Thema untersucht haben. Um die Notwendigkeit
frontaler Hirnareale im Hinblick auf die Verarbeitung von Konflikt zu
überprüfen, wurden in dieser Studie 11 Patienten mit frontalen
Hirnschädigungen mit 11 weiteren Patienten mit nicht-frontalen
Hirnschädigungen und 11 gesunden Kontrollpersonen hinsichtlich ihrer
Ergebnisse im Aufmerksamkeits-Netzwerk-Test (ANT), insbesondere im
Konflikteffekt, und in verschiedenen anderen neuropsychologischen Tests
verglichen. Signifikante Unterschiede zwischen den drei Gruppen fanden
sich im Konflikteffekt, im relativen Konflikteffekt sowie in der
durchschnittlichen Reaktionsgeschwindigkeit. Im Konflikteffekt und im
relativen Konflikteffekt ergaben sich mittlere Effektstärken im Vergleich der
frontalen Gruppe mit der nicht-frontalen Gruppe und große Effektstärken im
Vergleich der Patientengruppen mit der gesunden Kontrollgruppe. Diese
Ergebnisse deuten auf eine allgemeine Verlangsamung neurologischer
Patienten und Schwierigkeiten in Konfliktsituationen hin, welche allerdings
besonders bei Patienten mit frontalen Hirnschädigungen ausgeprägt sind.
Diese Dissoziation ergänzt die Ergebnisse von funktionellen
Magnetresonanztomographie (fMRT) -Studien (Fan et al., 2002, 2005, 2007,
2008) und beweist die Notwendigkeit dieser Hirnregionen für diese exekutive
Funktion.
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
24
6. References
Baird, A., Dewar, B. K., Critchley, H., Gilbert, S. J., Dolan, R. J. & Cipolotti, L.
(2006). Cognitive functioning after medial frontal lobe damage including
the anterior cingulate cortex: A preliminary investigation. Brain and
Cognition, 60, 166-175.
Barch, D. M., Braver, T. S., Akbudak, E., Conturo, T., Ollinger, J. & Synder,
A. (2001). Anterior cingulated cortex and response conflict: effects of
response modality and processing domain. Cerebral Cortex, 11(9), 837-
848.
Bates, E., Wilson, S. M., Saygin, A. P., Dick, F., Sereno, M. I., Knight, R. T. &
Dronkers, N. F. (2003). Voxel-based lesion-symptom mapping. Nature
Neuroscience, 6(5), 448-450.
Beck, L., Heusinger, A., Boecker, M., Niemann, H. & Gauggel, S. (2008).
Convergent and predictive validity oft two computerized attention tests
in brain-damged patients. Zeitschrift für Neuropsychologie, 19(4), 213-
222.
Berger, A. & Posner, M. I. (2000). Pathologies of brain attentional networks.
Neuroscience & Behavioral Reviews, 24(1), 3-5.
Beste, C., Saft C., Andrich, J., Gold,R. & Falkenstein, M. (2008). Stimulus-
response compatibility in Huntington´s disease: a cognitive-
neurophysiological analysis. Journal of Neurophysiology, 99(3), 1213-
1223.
Botvinick, M., Nystrom, L. E., Fissell, K., Carter C. S. & Cohen J. D. (1999).
Conflict monitoring versus selection-for-action in anterior cingulate
cortex. Nature, 402(6758), 179-181.
Botvinick, M., Cohen, J. D. & Carter, C. S. (2004). Conflict monitoring and
anterior cingulate cortex: an update. Trends in Cognitive Sciences,
8(12), 539-546.
Bunge, S. A., Hazeltine, E., Scanlon, M. D., Rosen, A. C. & Gabrieli, J. D.
(2002). Dissociable contributions of prefrontal and parietal cortices to
response selection. Neuroimage, 17(3), 1562-1571.
Bush, G., Frazier, J. A., Rauch S. L., Seidman L. J., Whalen, P. J., Jenike, M.
A., Rosen, B. R. & Biederman, J. (1999). Anterior cingulate cortex
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
25
dysfunction in attention-deficit/hyperactivity disorder revealed by fMRI
and the Counting Stroop. Biological Psychiatry, 45(12), 1542-1552.
Carter, C. S., Mintun, M., Nichols, T., Cohen & J. D. (1997). Anterior
cingulate gyrus dysfunction and selective attention deficits in
schizophrenia: [150]H2O PET study during single-trial Stroop task
performance. The American Journal of Psychiatry, 154(12), 1670-1675.
Carter, C. S., MacDonald, A. M., Botvinick, M., Ross, L. L., Stenger, V. A.,
Noll, D. & Cohen, J. D. (2000). Parsing executive processes: strategic
vs. evaluative functions of the anterior cingulate cortex. Proceedings of
the National Academy of Sciences of the United States of America,
97(4), 1944-1948.
Casey, B. J., Trainor, R. J., Orendi, J. L., Schubert A. B., Nystrom, L. E.,
Giedd, J. N., Castellanos, F. X., Haxby, J. V., Noll, D. C., Cohen, J. D.,
Forman, S. D., Dahl, R. E. & Rapoport, J. L. (1997) A Developmental
Functional MRI Study of Prefrontal Activation during Performance of a
Go-No-Go-Task. Journal of Cognitive Neuroscience, 9(6), 835-847.
Casey, B. J., Thomas, K. M., Welsh, T. F., Badgaiyan, R. D., Eccard, C. H.,
Jennings, J. R. & Crone, E. A. (2000). Dissociation of response conflict,
attentional selection, and expectancy with functional magnetic
resonance imaging. Proceedings of the National Academy of Sciences
of the United States of America, 97(15), 8728-8733.
Cohen, R. A., Kaplan, R. F., Zuffante, P., Moser, D. J., Jenkins, M. A.,
Salloway, S. & Wilkinson, H. (1999). Alteration of intention and self-
initiated action associated with bilateral anterior cingulotomy. The
Journal of Neuropsychiatry and Clinical Neurosciences, 11(4), 444-453.
Di Pellegrino, G., Ciaramelli, E. & Ládavas, E. (2007). The regulation of
cognitive control following rostral anterior cingulate cortex lesions in
humans. Journal of Cognitive Neuroscience, 19(2), 275-286.
Durston, S., Davidson, M. C., Thomas, K. M., Worden M. S., Tottenham N.,
Martinez A., Watts R., Ulug A.M. & Casey B. J. (2003). Parametric
manipulation of conflict and response competition using rapid mixed-
trial event-related fMRI. Neuroimage, 20(4), 2135-2141.
Egner, T. (2008). Multiple conflict-driven control mechanisms in the human
brain. Trends in Cognitive Sciences, 12(10), 374-380.
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
26
Eriksen, B. A. & Eriksen, C. W. (1974). Effects of noise letters upon the
identification of a target letter in a nonsearch task. Perception and
Psychophysics, 16, 143-149.
Fan, J., Wu, Y., Fossella, J. A. & Posner, M. I. (2001). Assessing the
heritability of attentional networks. BMC Neuroscience, 2:14.
Fan, J., McCandliss, B. D., Sommer, T., Raz, A. & Posner, M. I. (2002).
Testing the efficiency and independence of attentional networks.
Journal of Cognitive Neuroscience, 14(3), 340-347.
Fan, J., Fossella, J., Sommer, T., Wu, Y. & Posner, M. I. (2003). Mapping the
genetic variation of executive attention onto brain activity. Proceedings
of the National Academy of Sciences of the United States of America,
100(12), 7406-7411.
Fan, J., McCandliss, B. D., Fossella, J., Flombaum, J. I. & Posner, M. I.
(2005) The activation of attentional networks. Neuoimage, 26(2), 471-
479.
Fan, J., Kolster, R., Gahjar, J., Suh, M., Knight, R. T., Sarkar, R. &
McCandliss, B. D. (2007). Response anticipation and response conflict:
an event-related potential and functional magnetic resonance imaging
study. Journal of Neuroscience, 27(9), 2272-2282.
Fan, J., Hof, P. R., Guise, K. G., Fossella, J. A. & Posner, M. I. (2008). The
functional integration of the anterior cingulate cortex during conflict
processing. Cerebral Cortex, 18(4), 796-805.
Fellows, L. K. & Farah, M. J. (2005). Is anterior cingulate cortex necessary
for cognitive control? Brain, 128(Pt 4), 788-796.
Gooding, D. C., Braun, J. G. & Studer, J. A. (2006). Attentional network task
performance in patients with schizophrenia-spectrum disorders:
evidence of a specific deficit. Schizophrenia Research, 88(1-3), 169-
178.
Haupt, S., Axmacher, N., Cohen, M. X., Elger, C. E. & Fell, J. (2009).
Activation of the vaudal anterior cingulate cortex due to task-related
interference in an auditory Stroop paradigm. Human Brain Mapping,
30(9), 3043-3056.
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
27
Hazeltine, E., Poldrack, R. & Gabrieli, J. D. (2000). Neural activation during
response competition. Journal of Cognitive Neuroscience, 12 Suppl 2,
118-129.
Hazeltine, E., Bunge, S. A., Scanlon, M. D. & Gabrieli, J. D. (2003). Material-
dependent and material-independent selection processes in the frontal
and parietal lobes: an event-related fMRI investigation of response
competition. Neuropsychologia, 41(9), 1208-1217.
Helmstaedter, C., Lendt, M. & Lux, S. (2001). Verbaler Lern- und
Merkfähigkeitstest (VLMT). Hogrefe Verlag: Beltz Test GmbH.
Hochstenbach, J., Mulder, T., van Limbeek, J., Donders, R. &
Schoonderwaldt, H. (1998). Cognitive decline following stroke: A
comprehensive study of cognitive decline following stroke. Journal of
Clinical and Experimental Neuropsychology, 20, 503-517
Holmes, A. J. & Pizzagalli, D. A. (2008). Response conflict and
frontocingulate dysfunction in unmediated participants with major
depression. Neuropsychologia, 46(12), 2904-2913.
Horn, W. (1983). Leistungsprüfsystem (LPS). Handanweisung (2., erweiterte
und verbesserte Auflage). Hogrefe Verlag: Beltz Test GmbH.
Kerns, J. G., Cohen, J. D., MacDonald, A. W. 3rd, Cho, R. Y., Stenger, V. A.
& Carter, C. S. (2004). Anterior cingulate conflict monitoring and
adjustments in control. Science, 303(5660), 1023-1026.
Konrad, K., Neufang, S., Thiel, C. M., Specht, K., Hanisch, C., Fan, J.,
Herpertz-Dahlmann, B. & Fink, G. R. (2005) Neuroimage, 28(2), 429-
439.
Lau, H., Rogers, R. D. & Passingham, R. E. (2006). Dissociating response
selection and conflict in the medial frontal surface. Neuroimage, 29(2),
446-451.
Luks, T. L., Simpson, G. V., Dale, C. L. & Hough, M. G. (2007). Preparatory
allocation of attention and adjustments in conflict processing.
Neuroimage, 35(2), 949-958.
MacDonald, A. W. 3rd, Cohen, J. D., Stenger, V. A. & Carter, C. S. (2000).
Dissociating the role of the dorsolateral prefrontal and anterior cingulate
cortex in cognitive control. Science, 288(5472), 1835-1838.
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
28
McNab, F., Leroux, G., Strand, F., Thorell, L., Bergman, S. & Klingberg, T.
(2008). Common and unique components of inhibition and working
memory: an fMRI, within-subjects investigation. Neuropsychologia,
46(11), 2668-2682.
Miller, J. S. & Cohen, M. A. (2001). An integrative Theory of prefrontal cortex
function. Annual Review of Neuroscience, 24, 167-202.
Norman, D. A. & Shallice, T. (1986). Attention to action: willed and automatic
control of behavior. In Consciousness and self regulation (ed. R.J.
Davidson, G. E. Schwartz and D. Shapiro), pp. 1-18. New York: Plenum
Press.
Ochsner, K. N., Hughes, B., Robertson, E. R., Cooper, J. C. & Gabrieli, J. D.
(2009). Neural systems supporting the control of affective and cognitive
conflicts. Journal of Cognitive Neuroscience, 21(9), 1842-1855.
Ponsford, J. &Kinsella, G. (1992). Attentional deficits following closed-head
injury. Journal of Clinical and Experimental Neuropsychology, 14, 822-
838
Posner, M. I. (1980). Orienting of attention. Quarterly Journal of Experimental
Psychology, 41A, 19-45.
Posner, M. I. & DiGirolamo, G. J. (1998). Executive attention: conflict, target
detection and cognitive control. The Attentive Brain (Parasuraman, R.,
ed.), 401-423, MIT Press
Posner, M. I. & Rothbart, M. K. (1998). Attention, self-regulation and
consciousness. Philosophical Transactions of the Royal Society of
London B Biological Science, 353(1377), 1915-1927.
Posner, M. I., Rothbart, M. K., Vizueta, N., Levy, K. N., Evans, D. E.,
Thomas, K. M. & Clarkin, J. F. (2002). Attentional mechanisms of
borderline personality disorder. Proceedings of the National Academy of
Sciences of the United States of America, 99(25), 16366-16370.
Rafal, R., Gershberg, F., Egly, R., Ivry, R., Kingstone, A. & Ro, T. (1996).
Response channel activation and the lateral prefrontal cortex.
Neuropsychologia, 34(12), 1197-1202.
Reitan, R. M. (1955). The relationship of the Trail Making Test to organic
brain damage. Journal of Consulting Psychology, 19, 393-394.
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
29
Richter, W. (1999). High temporal resolution functional magnetic resonance
imaging at very-high-field. Topics in Magnetic resonance imaging,
10(1), 51-62.
Roberts, K. L. & Hall, D. A. (2008). Examining a supramodel network for
conflict processing: a systematic review and novel functional magnetic
resonance imaging data for related visual and auditory stroop tasks.
Journal of Cognitive Neuroscince, 20(6), 1063-1078.
Rorden, C., Karnath, H. O. & Bonilha, L. (2007). Improving lesion-symptom
mapping. Journal of Cognitive Neuroscience, 19(7), 1081-1088.
Shallice, T. & Burgess, P. W. (1991). Defecits in strategy application
following frontal lobe damage in man. Brain, 114(Pt 2), 727-741.
Snow, J. C. & Mattingley, J. B. (2006). Goal-driven selective attention in
patients with right hemisphere lesions: how intact is the ipsilesional
field? Brain, 129(Pt 1), 168-182.
Stuss, D. T., Bisschop, S. M., Alexander, M. P., Levine, B., Katz, D. &
Izukawa, D. (2001). The Trail Making Test: a study in focal lesion
patients. Psychological Assessment, 13(2), 230-239.
Stuss, D. T., Floden, D., Alexander, M. P., Levine, B. & Katz, D. (2001).
Stroop performance in focal lesion patients: dissociation of processes
and frontal lobe lesion location. Neuropsychologia, 39(8), 771-786.
Swick, D. & Jovanovic, J. (2002). Anterior cingulated cortex and the Stroop
task: neurophysiological evidence for topographic specifity.
Neuropsychologia, 40(8), 1240-1253.
Swick, D. & Turken, U. (2002). Dissociation between conflict detection and
error monitoring in the human anterior cingulate cortex. Proceedings of
the National Academy of Sciences of the United States of America,
99(25), 16354-16359.
Taylor, P.C., Nobre, A. C. & Rushworth, M. F. (2007). Subsecond changes in
top down control exerted by human medial frontal cortex during conflict
and action selection: a combined transcranial magnetic stimulation
electroencephalography study. Journal of Neuroscience, 27(42), 11343-
11353.
Ullsperger, M. & von Cramon, D. Y. (2004). Neuroimaging of performance
monitoring: error detection and beyond. Cortex, 49(4-5), 593-604.
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
30
Van Veen, V., Cohen, J. D., Botvinick, M. M., Stenger, V. A. & Carter, C. S.
(2001). Anterior cingulate cortex, conflict monitoring, and levels of
processing. Neuroimage, 14(6), 1302-1308.
Vendrell, P., Junqué, C., Pujol, J., Jurado, M.A., Molet, J. & Grafman, J.
(1995). The role of prefrontal regions in the Stroop task.
Neuropsychologia, 33(3), 341-352.
Wager, T. D., Sylvester, C. Y., Lacey, S. C., Nee, D. E., Franklin, M. &
Jonides, J. (2005). Common and unique components of response
inhibition revealed by fMRI. Neuroimage, 27(2), 323-340.
Wang, L., Liu, X., Guise, K. G., Knight, R. T., Ghajar, J. & Fan, J. (2010).
Effective connectivity of the fronto-parietal network during attentional
control. Journal of Cognitive Neuroscience, 22(3), 543-553.
Wühr, P. & Kunde, W. (2008). Precueing spatial S-R correspondence: is
there regulation of expected response conflict? Journal of Experimental
Psychology: Human Perception and Performance, 34(4), 872-883.
Wylie, S. A., Stout J. C. & Bashore T. R. (2005). Activation of conflicting
responses in Parkinson´s disease: evidence for degrading and
facilitating effects on response time. Neuropsychologia, 43(7), 1033-
1043.
Zahn, T. P. & Mirsky, A. F. (1999). Reaction time indicators of attention
deficits in closed head injury. Journal of Clinical and Experimental
Neuropsychology, 21, 352-367
Zysset, S., Müller, K., Lohmann, G. & von Cramon, D. Y. (2001). Color-word
matching stroop task: seperating interference and response conflict.
Neuroimage, 13(1), 29-36.
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
31
7. Appendix
7.1. List of tables
Table 1: Demographic and clinical data of patients with frontal lesions (FG),
patients with non-frontal lesions (NFG) and healthy controls (CG). ............... 7
Table 2: Neuropsychological data of patients with frontal lesions (FG),
patients with non-frontal lesions (NFG) and controls (CG). ………………....13
Table 3: Results of the ANT of patients with frontal lesions (FG), patients
with non-frontal lesions (NFG) and controls (CG). …………………………....14
Table 4: fMRI studies of the flanker task in healthy controls. …………….....33
Table 5: fMRI studies of the Stroop task in healthy controls. ……………….37
Table 6: Patients lesion localization. …………………………………………..39
Eva-Maria Meier
Selective impairment of the conflict network in patients with frontal lesions
32
7.2. List of figures
Figure 1: Brain areas that play an important role in handling with the
occurrence of conflict: frontal lobe (especially anterior cingulate gyrus and
dorsolateral prefrontal cortex) and parietal cortex (BrainVoyager Brain Tutor,
Version 2.0) ....................................................................................................4
Figure 2: Target conditions ............................................................................9
Figure 3: Cue conditions ................................................................................9
Figure 4: Schema of the ANT ......................................................................10
Figure 5: In MRIcron marked lesion. ............................................................11
Figure 6: Mean reaction time of patients with frontal lesions (FG), patients
with non-frontal lesions (NFG) and controls (CG). ........................................15
Figure 7: Accuracy of patients with frontal lesions (FG), patients with non-
frontal lesions (NFG) and controls (CG). ......................................................16
Figure 8: Conflict effect of patients with frontal lesions (FG), patients with
non-frontal lesions (NFG) and controls (CG). ...............................................16
Figure 9: Alerting effect of patients with frontal lesions (FG), patients with
non-frontal lesions (NFG) and controls (CG). ...............................................17
Figure 10: Orienting effect of patients with frontal lesions (FG), patients with
non-frontal lesions (NFG) and controls (CG). ...............................................17
Ev
a-M
aria
Me
ier
Se
lec
tive
im
pa
irm
en
ts o
f th
e c
on
flic
t n
etw
ork
in
pa
tie
nts
with
fro
nta
l le
sio
ns
33
7.3
. S
up
ple
me
nta
ry m
ate
ria
l
Tab
le 4
. fM
RI s
tudi
es o
f th
e fla
nker
task
in h
ealth
y co
ntro
ls.
Aut
hor
n D
esig
n R
esul
ts
Bot
vini
ck e
t al.
, 199
9 11
E
R
A
CC
Bun
ge e
t al.
, 200
2
10
ER
bi-lt
AC
C, b
i-lt P
CC
, bi-l
t MF
G, l
IFG
, bi-l
t SF
G, l
IPS
, bi-l
t PC
S, m
otor
, pre
mot
or a
nd
supp
lem
enta
ry m
otor
cor
tices
, bi-l
t tha
lam
us, r
pos
terio
r in
sula
Cas
ey e
t al.
, 200
0
8
B
r
AC
C, r
SF
G, l
MF
G, r
cau
date
nuc
leus
, ins
ular
cor
tex,
l su
perio
r pa
rieta
l lob
ule,
r
infe
rior
parie
tal l
obul
e, l
ST
G, r
cer
ebel
lum
Dur
ston
et a
l. , 2
003
9 E
R
bi
-lt A
CC
, l M
FG
, r S
FG
, bi-l
t sup
erio
r pa
rieta
l lob
e, r
intr
apar
ieta
l sul
cus,
l fu
sifo
rm
gyru
s
Ev
a-M
aria
Me
ier
Se
lec
tive
im
pa
irm
en
ts o
f th
e c
on
flic
t n
etw
ork
in
pa
tie
nts
with
fro
nta
l le
sio
ns
34
Aut
hor
n D
esig
n R
esul
ts
Fan
et a
l. , 2
003
12
E
R
bi
-lt c
ingu
late
gyr
us, r
pos
tcen
tral
gyr
us, l
MF
G, b
i-lt l
ingu
al g
yrus
, l p
rece
ntra
l gyr
us, r
infe
rior
parie
tal l
obul
e, l
post
cent
ral g
yrus
, bi-l
t SF
G, b
i-lt I
TG
, l S
TG
, r p
recu
neus
Fan
et a
l. , 2
005
12
E
R
r
AC
C, T
hala
mus
, l S
FG
, bi-l
t IF
G, b
i-lt f
usifo
rm g
yrus
, cer
ebel
lar
verm
is, r
MF
G
Fan
et a
l., 2
007
20
E
R
l A
CC
, bi-l
t MF
G, l
sup
erio
r pa
rieta
l lob
ule,
r p
recu
neus
, r M
FG
, r p
arac
entr
al lo
bule
Fan
et a
l. , 2
008
16
E
R
l A
CC
, r IF
G, r
sup
erio
r pa
rieta
l lob
ule,
l fu
sifo
rm g
yrus
, l in
sula
, l p
ostc
entr
al g
yrus
, r
thal
amus
(pu
lvin
ar)
Haz
eltin
e et
al.
, 200
0 8
B
r
infe
rior
pref
ront
al c
orte
x, l
supp
lem
enta
ry m
otor
cor
tex,
l su
perio
r pa
rieta
l cor
tex,
l
infe
rior
ante
rior
parie
tal c
orte
x
Haz
eltin
e et
al.
, 200
3 10
E
R
r
AC
C, r
IFG
, r M
FG
, r S
FG
, bi-l
t pre
mot
or c
orte
x, l
prec
entr
al
cort
ex, r
infe
rior
parie
tal c
orte
x
Ev
a-M
aria
Me
ier
Se
lec
tive
im
pa
irm
en
ts o
f th
e c
on
flic
t n
etw
ork
in
pa
tie
nts
with
fro
nta
l le
sio
ns
35
Aut
hor
n D
esig
n R
esul
ts
Lau
et a
l. , 2
005
16
B
AC
C
Luks
et a
l. , 2
007
11
E
R
bi
-lt A
CC
, bi-l
t pre
SM
A, b
i-lt I
PS
, r D
LPF
C, b
i-lt v
entr
olat
eral
PF
C, b
i-lt o
rbito
fron
tal
cort
ex
McN
ab e
t al.
, 200
8
14
B
l A
CC
, l c
orpu
s ca
llosu
m, r
infe
rior
parie
tal c
orte
x, r
sup
erio
r pa
rieta
l cor
tex
Och
sner
et a
l. , 2
009
16
B
bi
-lt M
FG
, r in
sula
, bi-l
t IF
G, b
i-lt p
rece
ntra
l gyr
us, l
cin
gula
te g
yrus
, l s
uper
ior
parie
tal l
obul
e, l
para
hipp
ocam
pal g
yrus
, bi-l
t pre
cune
us, l
SF
G, r
ST
G, r
cau
date
Van
Vee
n et
al.
, 200
1 12
E
R
A
CC
, l IF
C, b
i-lt D
LPF
C, r
par
ieta
l cor
tex,
l pr
ecun
eus,
pos
terio
r ci
ngul
ate
gyru
s, l
pola
r
fron
tal c
orte
x
Wag
er e
t al,
2005
14
ER
l par
ieta
l cor
tex,
bi-l
t ant
erio
r pr
efro
ntal
cor
tex,
l in
sula
, r A
CC
, bi-l
t cau
date
, bi-l
t
Put
amen
Ev
a-M
aria
Me
ier
Se
lec
tive
im
pa
irm
en
ts o
f th
e c
on
flic
t n
etw
ork
in
pa
tie
nts
with
fro
nta
l le
sio
ns
36
Aut
hor
n D
esig
n R
esul
ts
Wan
g et
al.
, 201
0
18
B
bi
-lt A
CC
, r m
iddl
e ci
ngul
ate
cort
ex, r
pos
tcen
tral
gyr
us, r
SF
G, r
MF
G, l
thal
amus
, l
IFG
, l p
rece
ntra
l gyr
us, l
infe
rior
parie
tal g
yrus
ER
= e
vent
-rel
ated
des
ign;
B =
blo
ck d
esig
n; l
= le
ft; r
= r
ight
; bi-l
t = b
ilate
ral
AC
C =
ant
erio
r ci
ngul
ate
cort
ex,
PC
C =
po
ster
ior
cing
ulat
e co
rtex
, M
FG
= m
edia
l fr
onta
l gy
rus;
IF
G =
inf
erio
r fr
onta
l gy
rus;
SF
G =
supe
rior
fron
tal
gyru
s; I
PS
= i
nfer
ior
parie
tal
sulc
us;
PC
S =
pos
tcen
tral
sul
cus;
ST
G =
sup
erio
r te
mpo
ral
gyru
s; I
TG
= i
nfer
ior
tem
pora
l
gyru
s; D
LPF
C =
dor
sola
tera
l pre
fron
tal c
orte
x; S
MA
= s
uppl
emen
tary
mot
or a
rea
Ev
a-M
aria
Me
ier
Se
lec
tive
im
pa
irm
en
ts o
f th
e c
on
flic
t n
etw
ork
in
pa
tie
nts
with
fro
nta
l le
sio
ns
37
Tab
le 5
. fM
RI s
tudi
es o
f th
e S
troo
p ta
sk in
hea
lthy
cont
rols
.
Aut
hor
n
Des
ign
R
esul
ts
Bar
ch e
t al.,
200
1
13
E
R
l AC
C, S
MA
, pre
-SM
A
Car
ter
et a
l., 2
000
12
ER
A
CC
, l IP
C, b
i-lt I
FC
, ext
rast
riate
vis
ual c
orte
x
H
aupt
et a
l., 2
009
29
B
bi-lt
DLP
FC
, l in
sula
, l c
ingu
late
gyr
us, l
lent
iform
nuc
leus
, l M
FG
, l
Tha
lam
us, l
AC
C, p
re-S
MA
, SF
G
Ker
ns e
t al.,
200
4
23
E
R
AC
C, l
fro
ntal
cor
tex,
r IP
C, b
i-lt M
FG
, r p
arie
tal c
orte
x, l
ST
G,
r
puta
men
, l M
TG
, l th
alam
us, b
i-lt I
FG
Mac
Don
ald
et a
l., 2
000
12
E
R
AC
C, l
DLP
FC
Ev
a-M
aria
Me
ier
Se
lec
tive
im
pa
irm
en
ts o
f th
e c
on
flic
t n
etw
ork
in
pa
tie
nts
with
fro
nta
l le
sio
ns
38
Aut
hor
n D
esig
n R
esul
ts
Rob
erts
et a
l., 2
008
16
B
bi-lt
late
ral P
FC
, AC
C, l
eft p
rem
otor
cor
tex,
l su
perio
r pa
rieta
l lob
ule,
l
infe
rior
parie
tal l
obul
e, p
recu
neus
, r IF
G, r
ant
erio
r in
sula
cor
tex
Zys
set e
t al.,
200
1
9
B
l pos
terio
r in
ferio
r fr
onta
l sul
cus,
bi-l
t occ
ipito
tem
pora
l gyr
us, l
cun
eus
ER
= e
vent
-rel
ated
des
ign;
B =
blo
ck d
esig
n; l
= le
ft; r
= r
ight
; bi-l
t = b
ilate
ral
AC
C =
ant
erio
r ci
ngul
ate
cort
ex, I
PC
= in
ferio
r pa
rieta
l cor
tex,
MF
G =
med
ial f
ront
al g
yrus
, ST
G =
sup
erio
r te
mpo
ral g
yrus
, MT
G =
med
ial t
empo
ral
gyru
s, D
LPF
C =
dor
sola
tera
l pre
fron
tal c
orte
x, S
MA
= s
uppl
emen
tary
mot
or a
rea,
PF
C =
pre
fron
tal c
orte
x, IF
G =
infe
rior
fron
tal g
yrus
Ev
a-M
aria
Me
ier
Se
lec
tive
im
pa
irm
en
ts o
f th
e c
on
flic
t n
etw
ork
in
pa
tie
nts
with
fro
nta
l le
sio
ns
39
Tab
le 6
. Pat
ient
s le
sion
loca
lizat
ion
in th
e pr
esen
t stu
dy.
Pat
ient
G
roup
E
tiolo
gy
Le
sion
loca
lizat
ion
Le
sion
siz
e
H
emis
pher
e
Reg
ion
(cc)
91
F
G
st
roke
left
Gyr
us p
raec
entr
alis
0.3
98
F
G
tu
mor
right
G
yrus
fro
ntal
is s
uper
ior
33
.74
le
ft
pa
ram
edia
n ce
ntra
l reg
ion
Gyr
us f
ront
alis
sup
erio
r
Gyr
i occ
ipita
les
155
F
G
tu
mor
left
Gyr
us f
ront
alis
infe
rior
78
.41
199
F
G
st
roke
right
fr
onta
l Ope
rcul
um, d
iffer
ent p
arts
of
90
.64
the
fron
tal c
orte
x
315
F
G
st
roke
left
Gyr
us p
ostc
entr
alis
up
to p
arie
tal
24
.88
and
fron
tal O
perc
ulum
Ev
a-M
aria
Me
ier
Se
lec
tive
im
pa
irm
en
ts o
f th
e c
on
flic
t n
etw
ork
in
pa
tie
nts
with
fro
nta
l le
sio
ns
40
Pat
ient
G
roup
E
tiolo
gy
Le
sion
loca
lizat
ion
Le
sion
siz
e
H
emis
pher
e
Reg
ion
(cc)
330
F
G
st
roke
left
fron
tal a
nd p
arie
tal O
perc
ulum
12
.55
346
F
G
st
roke
left
med
ulla
ry c
ente
r
3.
3
369
F
G
st
roke
left
ante
rior
terr
itoria
l str
oke
10.2
5
with
par
t of
the
Gyr
us fr
onta
lis s
uper
ior
423
F
G
st
roke
left
Cen
trum
sem
iova
le
1.
31
Str
iatu
m
117
N
FG
stro
ke
rig
ht
Cel
la m
edia
of
the
right
7.42
side
ven
tric
le u
p to
cor
tex
267
N
FG
stro
ke
le
ft
m
ultip
le d
isse
min
atin
g in
farc
ts in
the
2.15
terr
itory
of
the
mid
dle
cere
bral
art
ery
Ev
a-M
aria
Me
ier
Se
lec
tive
im
pa
irm
en
ts o
f th
e c
on
flic
t n
etw
ork
in
pa
tie
nts
with
fro
nta
l le
sio
ns
41
Pat
ient
G
roup
E
tiolo
gy
Le
sion
loca
lizat
ion
Le
sion
siz
e
H
emis
pher
e
Reg
ion
(cc)
313
N
FG
stro
ke
le
ft
pa
rieto
occi
pita
l
0.
62
336
N
FG
stro
ke
le
ft
m
edia
l occ
ipita
l lob
e
6.15
342
N
FG
stro
ke
le
ft
T
rigon
um
345
N
FG
stro
ke
rig
ht
Gyr
us p
ostc
entr
alis
2.3
347
N
FG
stro
ke
rig
ht
mar
row
bed
1.64
Tha
lam
us, P
utam
en
mes
ence
phal
348
N
FG
stro
ke
rig
ht
tem
poro
-par
ieta
l
31
.84
Ev
a-M
aria
Me
ier
Se
lec
tive
im
pa
irm
en
ts o
f th
e c
on
flic
t n
etw
ork
in
pa
tie
nts
with
fro
nta
l le
sio
ns
42
Pat
ient
G
roup
E
tiolo
gy
Le
sion
loca
lizat
ion
Le
sion
siz
e
H
emis
pher
e
Reg
ion
(cc)
349
N
FG
stro
ke
rig
ht
Put
amen
0.27
post
erio
r cr
us o
f th
e in
tern
al c
apsu
le
subi
nsul
e co
rtex
med
ial t
empo
ral l
obe
(with
Hip
poca
mpu
s)
350
N
FG
stro
ke
le
ft
C
entr
um s
emio
vale
368
N
FG
stro
ke
le
ft
m
arro
w b
ed
0.
68
FG
= f
ront
al g
roup
, NF
G =
non
-fro
ntal
gro
up, c
c =
cub
ic c
entim
etre
Eva-Maria Meier
Selective impairments of the conflict network in patients with frontal
lesions
43
9. Danksagung
Mein Dank gilt allen, die das Entstehen meiner Dissertation gefördert
haben, insbesondere meinem Betreuer Prof. Dr. Siegfried Gauggel. Ein
großer Dank geht auch an Frau Dr. Maren Böcker für ihre fachliche und
tatkräftige Unterstützung, insbesondere bei der Einarbeitung in das
Statistikprogramm SPSS. Außerdem danke ich Dr. Mario Städtgen für die
Einarbeitung in das Programm MRIcron, sowie der neurologischen Klinik
des Uniklinikums Aachen für die Bereitstellung der Patienten.
Eva-Maria Meier
Selective impairments of the conflict network in patients with frontal
lesions
44
8. Erklärung § 5 Abs. 1 zur Datenaufbewahrung
Hiermit erkläre ich, dass die dieser Dissertation zu Grunde liegenden
Originaldaten im
Institut für Medizinische Psychologie und Medizinische Soziologie,
Universitätsklinikum der RWTH Aachen,
Pauwelsstraße 30, 52074 Aachen
hinterlegt sind.
Eva-Maria Meier
Selective impairments of the conflict network in patients with frontal
lesions
45
9. Curriculum vitae Name: Eva-Maria Meier
Geburtsdatum: 14.02.1985
Geburtsort: Paderborn
Nationalität: deutsch
Familienstand: ledig
Email: [email protected]
Schulischer Werdegang:
1991 – 1995 Grundschule Delbrück-Ostenland
1995 – 2004 Gymnasium Schloß-Neuhaus
2004: Allgemeine Hochschulriefe (Note: 1,5)
06 – 08/2002 Auslandaufenthalt in Chile:
Gastschülerin an der Deutschen Schule in Santiago
de Chile
Hochschule:
WS 2004/2005 bis Studium der Humanmedizin an der RWTH Aachen
WS 2010/2011
09/2007 Ärztliche Basisprüfung (Note: Gut)
11/2010 Zweiter Abschnitt der Ärztlichen Prüfung (Note:
Sehr gut )