Supplementum
Content
1. Patients and Methods
2. Descriptive statistics of cerebral blood flow velocity
3. Correlation analyses
4. References
1. Patients and Methods
1.1. Study population
1.1.1. Inclusion and exclusion criteria:
Inclusion criterion: Diagnosis of schizophrenia (DSM-IV)
Exclusion criteria: 1) affective or organic brain disorders, 2) substance abuse for the last 3 months prior
to the examination or a lifetime diagnosis of substance dependence, including a positive urine test for
psychotropic substances, 3) mental retardation, 4) migraine and other headaches.
1.1.2. Medication - name (mean dosage):
Typicals: Flupentixol (5.00 mg), haloperidol (3.50 mg), promazine (25.00 mg), zuclopenthixole (25.00
mg)
Atypicals: Amisulpride (400.00 mg), clozapine (281.25 mg), olanzapine (17.50 mg), quetiapine (650.00
mg), risperidone (4.40 mg)
1.2. Technical procedures
A second monitor was positioned beside the test screen. Before and after the Stockings of Cambridge
(SOC), subjects were told to watch that monitor which was running a conventional screen saver
(starfield, Microsoft Corp., USA) (Schuepbach et al., 2002a).
1.3. Cognitive paradigm
The Stockings of Cambridge (SOC) was presented on a touch-screen monitor with an upper part (goal
state) and a lower part (start state) each containing three pockets (stockings) of different sizes
(Schuepbach et al., 2007), on the left there was space for three balls, in the middle for two and on the
right for one ball. Each pocket contained a dedicated number of differently colored balls (blue, green and
red), and the total number of balls was always three. The goal of this task was to achieve an identical
configuration of balls as in the upper part of the screen by moving one ball at a time. Easy tasks were
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solved with a minimum number of moves of two or three, and difficult tasks with four or five moves
(Frauenfelder et al., 2004). After each trial, there was a pause of 20 s. A SOC task consisted of a two,
three, four, and five move problem with two different trials per problem, respectively. Each SOC task
started with a two move problem while the following three, four and five move problems were presented
in random order (Schuepbach et al., 2007). To avoid learning effects, trials were different for a distinct
difficulty level. Subjects were instructed a two-step sequence: First, to plan the moves necessary to solve
the tasks (mental planning) and, second, then carry out the moves (movement execution). There was a
control task to match the number of moves as presented by the planning task. It contained the same
number of trials and was inserted as follows: at the end of the SOC task and only once in between if an
easier problem followed a more difficult one. Hence, the SOC control task was designed to assess the
visuomotor component of the SOC task (visuomotor control).
All subjects received ample instructions on how to solve the task and also a practice session of several
one and two move problems. Subjects were asked to solve the task efficiently after having created a
plan.
1.4. Data collection
1.4.1. Performance
We collected the following parameters (Schuepbach et al., 2007): a) adjusted planning time, i.e. the time
needed to develop a movement sequence to solve the task minus the respective initiation time during
visuomotor control. b) The subsequent time, a means of time to carry out the mental plan, i.e. the time
spent from touching the first ball until completion of the task. c) Average moves above minimum
number of moves: This constitutes a means of task accuracy. Results from a study in healthy subjects
suggested that two and three move problems were mostly solved in the minimum number of moves
(Frauenfelder et al., 2004); whereas four and five move problems needed more moves. Therefore, we
introduced two categories of planning problems: easy problems (two and three move problems), and
difficult problems (four and five move problems).
1.4.2. Mean blood flow velocity (MFV)
Offline analysis of MFV comprised the following steps (Schuepbach et al., 2007): (a) integration of
absolute MFV to one value per heartbeat, (b) offline export of the digitized MFV data to a commercially
available spreadsheet program (MS-Excel, Microsoft Corp., USA), (c) normalization of digitized data
with reference to pre- and post-task rest phases and recalculation to percent values, i.e. relative MFV
values, (d) conversion from heartbeat to second-wise frequency. All MFV values in this paper are
relative MFV.
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2. Descriptive statistics of MFV (%) time course during the Stockings of Cambridge
a) Easy conditions
time(s)
I. Left hemisphere
Planning
Patients–no EPS
(n=8)
Patients-EPS healthy subjects
(n=8)
(n=16)
0
1
2
-0.68  3.73
-0.54  4.50
1.71  5.20
0.01  5.02
0.53  5.51
1.48 4.65
2.88  7.23
5.10  6.63
7.29  6.53
Movement execution
0
1
2
6.32  6.04
7.28  5.51
7.96  4.61
7.32  6.27
9.04  8.08
9.00  7.56
8.53  6.15
9.69  6.39
9.28  6.66
Control
0
1
2
-1.08  6.73
-0.98  7.68
0.65  7.93
0.78  6.98
1.30 6.94
2.61  6.44
0.61  5.51
2.34  6.40
3.79  5.82
time(s)
II. Right hemisphere
Planning
Patients-no EPS
(n=8)
Patients-EPS healthy subjects
(n=8)
(n=16)
0
1
2
1.01  3.93
1.25  5.16
3.93  5.59
-0.49  6.00
0.07  6.28
0.87  5.42
3.62  6.29
6.04  6.66
8.22  7.06
Movement execution
0
1
2
8.65  5.57
9.45  5.27
9.74  4.64
6.72  5.97
7.76  7.80
7.88  6.97
9.49  6.74
10.03  7.12
9.68  7.25
Control
0
1
2
0.65  5.60
0.75  6.32
2.82  6.91
-0.18  7.03
0.70  7.76
1.62  7.23
0.65  5.68
2.20  6.03
4.49  6.15
b) Difficult conditions
time(s)
I. Left hemisphere
Planning
Patients–no EPS
(n=8)
Patients-EPS healthy subjects
(n=8)
(n=16)
0
1
2
-2.27  3.56
-3.47  4.16
-2.44  3.85
1.33  3.67
2.48  4.60
3.17 6.05
1.59  6.18
2.98  6.29
4.99  7.46
Movement execution
0
1
2
5.21  5.47
6.17  5.28
6.45  5.40
4.78  5.31
4.49  5.92
4.20  6.40
8.45  7.83
9.29  8.45
9.46  8.61
Control
0
1
2
0.50  5.44
-0.37  5.65
-0.91  5.33
-0.10  5.92
0.17  4.84
1.20  4.02
0.84  6.95
1.04  6.80
2.60  5.96
time(s)
II. Right hemisphere
Planning
Patients-no EPS
(n=8)
Patients-EPS healthy subjects
(n=8)
(n=16)
0
1
2
-1.12  4.42
-2.45  4.36
-0.61  3.92
0.69  5.92
1.90  5.88
2.68  5.20
1.34  7.09
2.96  6.61
5.42  7.78
Movement execution
0
1
2
7.36  5.64
8.68  5.63
8.47  5.90
3.16  5.79
2.74  7.16
2.86  7.36
8.42  6.23
8.45  6.59
8.44  6.62
Control
0
1
2
0.79  5.48
0.46  6.36
0.44  6.87
-0.93  4.99
-1.31  4.03
-0.11  4.39
1.51  7.67
2.00  7.42
3.40  6.03
Values are mean values (%)  SD. Abbreviations: EPS, extrapyramidal symptoms; MFV, mean cerebral blood flow velocity
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3. Correlation analyses
a. Correlation between EPS-Score and MFV difference between movement execution and mental
planning.
Figure legend. Higher EPS-Score is significantly associated with decreased MFV difference between
movement execution and mental planning. Scatter plot between the score of extrapyramidal symptoms
and bilateral MFV difference (movement execution - mental planning). Solid line: regression model,
dashed lines: 95% confidence intervals. *P=0.027. Abbreviations: EPS, extrapyramidal symptoms;
MFV, mean cerebral blood flow velocity; R, Pearson’s product moment correlation coefficient.
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b. Correlation between EPS-Score and MFV difference between movement execution and mental
planning - Patients on atypical antipsychotics.
Figure legend. Higher EPS-Score is significantly associated with decreased MFV difference between
movement execution and mental planning – in patients on atypical antipsychotics. Scatter plot between
the score of extrapyramidal symptoms and bilateral MFV difference (movement execution - mental
planning). Solid line: regression model, dashed lines: 95% confidence intervals. *P=0.029.
Abbreviations: EPS, extrapyramidal symptoms; MFV, mean cerebral blood flow velocity; R, Pearson’s
product moment correlation coefficient.
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4. References
Frauenfelder BA, Schuepbach D, Baumgartner RW, Hell D (2004). Specific alterations of cerebral
hemodynamics during a planning task: A transcranial Doppler sonography study. Neuroimage 22:1223–
1230.
Schuepbach D, Weber S, Kawohl W, Hell D (2007). Impaired rapid modulation of cerebral
hemodynamics during a planning task in schizophrenia. Clin Neurophysiol 118:1449–1459.
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