A.4 Discussion
B.2.2 Design, Procedure, Recordings
-Patient08 295.3 - Flupentixol 2% 0.75 ml /
14d
Patient09 295.4
305.2
-
-Patient10 295.3 - Flupentixol 2% 2ml/14d
Table B-4: DSM-IV diagnosis and medication of each patient.
The mean neuroleptic dosage in chlorpromazine equivalents (Jahn &Mussgay, 1989; Woods, 2003) was 493.9 mg/day (SD: 430.6 mg/day).
B.2.2 Design, Procedure, Recordings
Patients were recruited for the study by the staff of the research ward and were paid 25 DEM (about 13 Euros) for participation. It was emphasized that the participation in the study was independent from treatment. The design, procedure and recordings were identical to the ones described in Part A of this thesis. No additional instructions were given to the patient group.
B.2.3 Analysis
Data were processed as described in Part A of this thesis. The same methods were applied, includ-ing the spatio-temporal correlation, unsupervised hierarchical clusterinclud-ing and self-organizinclud-ing map-ping. Groups did not differ in the number of trials included in the analysis (F(1,18)=1.01, p>.32).
On average, for controls 49.7 (SD: 4.4) out of 60 trials entered the grand average for each objects vs. 47.7 (SD: 4.9) trials for the patient group.
Statistical comparisons by means of ANOVA additionally included the factor GROUP for compar-70
B.2.3 : Methods - Analysis
isons between controls and patients5.
B.3 Results
B.3.1 Behavioral data
Figure B-1 shows the median response times and the number of correct responses for each category separated by group.
There was a tendency for slower responses in schizophrenia (GROUP: F(1,18)=4.31; p<.06; con-trols: 557.0 ms (SD: 60.7 ms); patients: 605.4 ms (SD: 41.9 ms), which was independent of the cat-egory (GROUP x CATEGORY, F(3,54)<1). Response times differed between categories (CATE-GORY, F(3,54)=4.47; p<.03). Post-hoc t-tests revealed that subjects responded faster to ‘animals’
and ‘furniture’ compared to clothing (animal vs. clothing: t(19) =2.96, p<.01; furniture vs. clothing:
t(19)=4.66, p = .001) and faster to animals compared to flower (t(19)=2.30, p<.04).
All comparisons of error rate differences were non-significant (CATEGORY, GROUP,
CATEGO-5 For group comparison of event-related potentials amplitude normalization procedures have been suggested if
inferences about source configurations are made from surface recordings (McCarthy & Woods, 1985). However, in the present study, sources were evaluated on the basis of the MNE, and simulations by Urbach & Kutas (2002) have shown that vector scaling fails in the application to ERP data. Following the recommendations by Urbach & Kutas (2002) no Figure B-1: Median response times in milliseconds (ms) for each of the four categories (left panel) and number (out of 240) and percentage of correct responses (right panel). Error bars represent one standard error. Response data for the control subjects is shown in the upper half and for the schizophrenic patients in the lower half.
B.3.1 : Results - Behavioral data
RY x GROUP: all F <1). Table B-5 summarizes response times and the number of correct respons-es for each object:
RT (ms) % correct
Controls Patients Controls Patients
Bear 559.4 (55.1) 591.8 (37.9) 94.0 (3.6) 93.7 (3.3) Deer 558.9 (61.9) 596.4 (44.5) 92.8 (4.4) 94.2 (5.5) Fox 552.0 (52.7) 600.7 (57.8) 94.2 (4.5) 94.0 (3.9) Wolf 554.7 (64.6) 592.6 (46.6) 92.3 (8.3) 95.2 (3.9) Orchid 576.6 (59.8) 619.1 (44.0) 94.5 (5.8) 92.0 (6.2) Rose 549.6 (52.0) 613.0 (43.0) 92.5 (6.4) 92.7 (6.2) Sunflower 545.4 (47.1) 600.5 (40.8) 93.2 (6.9) 92.7 (4.5) Tulip 557.3 (52.7) 594.2 (38.8) 94.2 (4.7) 93.3 (6.5) Jacket 569.0 (81.7) 611.9 (39.3) 93.8 (3.7) 90.0 (6.0) Shirt 574.7 (77.9) 616.2 (42.6) 92.2 (5.4) 91.2 (4.9) Shoe 561.4 (60.1) 619.2 (49.3) 94.2 (4.9) 90.8 (5.3) Trousers 569.4 (80.4) 612.8 (46.7) 95.7 (4.2) 94.8 (4.0) Chair 541.9 (61.7) 598.9 (48.8) 94.3 (4.4) 92.8 (4.7) Sofa 542.8 (66.5) 600.4 (44.9) 95.0 (4.5) 93.8 (5.0) Table 544.4 (64.5) 604.6 (46.6) 95.5 (3.9) 94.5 (5.2) Wardrobe 560.6 (66.9) 607.1 (50.9) 93.7 (3.4) 93.8 (4.7)
Table B-5: Median response times in milliseconds (ms) for each base-level concept and percentage of correct responses. Standard deviations are given in parenthesis.
ANOVA revealed no difference or interaction in the number of correct responses between groups and objects. On average, controls showed a mean error rate of 6.1 % and patients of 6.9 %
(GROUP: F(1,18) < 1). Response times differed between objects (F(15, 270)=4.19), p>.01), inde-pendent of the factor GROUP (OBJECT x GROUP: F(15,270)=1.20, n.s.). Post-hoc contrasts be-tween objects revealed significant differences bebe-tween several objects. Subjects categorized shirts statistically significant slower than chairs, tables and wardrobes, and tables were categorized faster compared to shoes. Moreover, the response time to orchids was increased compared to wolves and sunflowers (all p<.05 after alpha-adjustment according to Sidak).
Response times and error rates for each object were not correlated, neither for control subjects (r=.00) or patients (r=-.01), nor for the overall sample (r=.03). This indicates that there was no speed-accuracy tradeoff.
72
B.3.1 : Results - Behavioral data
To summarize, schizophrenia patients showed slower response times than controls. Groups did not differ in the number of errors made.
B.3.2 Evoked magnetic fields
B.3.2.1 Signal space
Figure B-2 illustrates the waveforms of the neuromagnetic response for a subset of posterior sensors for both groups. Waveforms show more pronounced deflections for the control group (e.g. see Sen-sor 87 or 106).
For several time windows (width 40 ms), statistical comparisons revealed significant interactions of the factors group and category with topographical factors. These are summarized in Table B-6. A complete Table with exact F and p values can be found in Appendix D.
Figure B-2: Averaged evoked magnetic field by semantic category for a subset of posterior sensor. Left panel: controls (n=10), right panel: patients (n=10).
B.3.2 : Results - Evoked magnetic fields Time
window (ms)
Highest –order interaction Main effects and interactions of lower order 090-130 Hemisphere x Depth x Group Hemisphere , Depth, Group
Hemisphere x Depth x Gradient Hemisphere, Depth 130-170 Category x Hemisphere x Depth Depth
170-210 Hemisphere x Depth x Gradient x Group
Hemisphere x Depth x Gradient Depth x Gradient x Group Category x Depth x Gradient
Category x Hemisphere x Depth Category x Hemisphere 210-250 Hemisphere x Depth x Gradient x
Group
Hemisphere x Depth x Gradient, Hemisphere x Gradient,
Hemisphere x Depth, Depth 250-290 Hemisphere x Depth x Gradient x
Group Hemisphere x Depth x Gradient,
Hemisphere x Gradient, Depth Category x Hemisphere x Depth x
Group
Category x Hemisphere x Depth, Category x Hemisphere x Group, Category , Depth
Category x Depth x Gradient x Group Category x Depth x Gradient, Category, Depth
290-330 Hemisphere x Depth x Gradient x
Group Hemisphere x Depth x Gradient,
Hemisphere x Gradient, Depth Category x Depth x Gradient Depth
Category x Hemisphere x Depth Category x Hemisphere, Depth Category x Hemisphere x Group Category x Hemisphere
330-370 Hemisphere x Depth x Gradient x Group
Hemisphere x Depth x Grad Hemisphere x Depth
Hemisphere
Category x Depth x Gradient x Group Category x Depth x Gradient Category x Hemisphere x Depth Hemisphere x Depth
Category x Hemisphere Hemisphere
370-410 Hemisphere x Depth x Gradient x
Group Hemisphere x Depth x Gradient
Hemisphere x Gradient Hemisphere x Depth Hemisphere
Category x Depth x Grad Category
Category x Hemisphere x Depth Category x Hemisphere, Hemisphere, Category,
410-450 Hemisphere x Depth x Gradient x
Group Hemisphere x Depth x Gradient,
Hemisphere x Gradient, Hemisphere x Depth, Hemisphere, Depth,
Category x Depth x Gradient x Group Category x Depth x Gradient
Category x Hemisphere x Gradient Hemisphere x Gradient, Category x Hemisphere, Hemisphere, Category, Category x Hemisphere x Depth Hemisphere x Depth, Depth, Hemisphere,
Category
Table B-6: Significant interactions and main effects for the comparison of evoked magnetic fields.
74
B.3.2 : Results - Evoked magnetic fields
The overall distribution of the magnetic field differed between groups as indicated by a HEMI-SPHERE x DEPTH x GRADIENT x GROUP interaction, which reached significance for all time windows from 170 to 450 ms (all F(2,36)>4.68; all p<.05). Post-hoc tests revealed that the interac-tion HEMISPHERE x DEPTH x GRADIENT was significant for control subjects (for all time win-dows between 170 and 450 ms), but not for schizophrenic patients. This indicates that control sub-jects showed a more distinct distribution of the magnetic field (see also A.3.2.1).
Earlier, between 90 and 130 ms after stimulus onset, the interaction HEMISPHERE x DEPTH x GROUP reached significance (F(2,36)=3.93; p,.04). Separate statistical comparisons for each group indicate that the HEMISPHERE x DEPTH interaction was only significant for the schizophrenic group, which showed more outgoing magnetic flux for the ‘ventral’ sensors over the right hemi-sphere.
Moreover, topographical differences between categories differed between groups for several later time intervals (CATEGORY x DEPTH x GRAD x GROUP (330-370; 370-410; 410-450; all F(6,108)>2.95, all p<.03) ; CATEGORY x HEMISPHERE x DEPTH x GROUP, (250-290:
F(6,108)=3.55; p<.02); CATEGORY x HEMISPHERE x GROUP , 290-330: F(3,54)=2.73,p<.06).
Post-hoc testing revealed that these interactions of CATEGORY with topographical factors were significant only for control subjects. None of the effects reached significance when testing was per-formed for the schizophrenic subgroup. Additionally, for control subjects separate subtests by CAT-EGORY were performed for the aforementioned interactions. None of the categories interacted sig-nificantly with topographical effects, indicating that in the signal space there was no category-spe-cific distribution of the magnetic evoked response.
B.3.2.2 Source space
The average across all categories was subtracted from each category to remove non-category
specif-B.3.2 : Results - Evoked magnetic fields
ic activity. The Minimum Norm Estimate was computed from the resulting difference. The topo-graphical distribution for each category across time is shown in Figure B-3 (for controls) and Figure B-4 (for patients).
Statistical testing by means of ANOVA revealed an interaction DEPTH x GROUP for the time win-dows 90-130 ms (F(2,36)=5.37, p<.02) and 250-290 ms (F(2,36)=3.62, p,.05. For the later time window, post-hoc testing showed non-significant results for both groups. However, for the earlier time window the factor DEPTH showed significant effects for the control subjects – activity in the most ventral areas was higher than in the neighboring more dorsal areas. (patients: F(2,18)=1.56, n.s.; controls: DEPTH: F(2,18)=4.16, p<0.05). 130-170 ms after the onset of the stimuli, there was a significant HEMISPHERE x DEPTH x GROUP interaction F(2,36)=3.49, p<.05). However, sepa-rate post-hoc tests showed, that for both groups the interaction of HEMISPHERE x DEPTH was not significant (controls: F(2,18)=2.25, p>.14; patients: F(2,18)=2.82,p=.10). Furthermore, a main ef-fect GROUP (F(1,18)=5.45, p<.04) was found (only for the time window 330-370 ms). Control sub-jects showed significantly higher dipole moments than patients (0.0043 vs. 0.0013 nAm/m2)
Figure B-3: veraged evoked magnetic field by semantic category for a subset of posterior sensor. Left panel: controls 76
(n=10), right panel: patients (n=10). Darker areas indicate higher dipole moments.
B.3.2 : Results - Evoked magnetic fields
B.3.3 Spatio-temporal correlations
Spatio-temporal correlations were computed to quantify similarities in the neuromagnetic activity between pairs of base-level concepts within pre-defined areas. Figure B-5 illustrates the mean Fis-cher’s Z-transformed correlation coefficients between each pair of base-level concepts for the right-temporal area in the time window starting 170 ms after stimulus onset.
Coefficients were further reduced by computing contrast scores (see A.2.4.4), and then mapped to a 2-D head model. Figure B-6 shows the topographical distribution of contrast scores during succes-sive time windows for both groups.
Figure B-4: Topographical distribution of the MNE of category-specific activity after the mean across all objects was subtracted (schizophrenic patients). Each row represents one time window. Topographies are shown in left, back and right view. Darker areas indicate higher dipole moments.
B.3.3 : Results - Spatio-temporal correlations
Figure B-6 shows the topographical distribution of contrast scores during successive time windows for both groups.
78
Figure B-5: Within- and between-category contrast scores for the right temporal region (area 12). Left panel: healthy controls, right panel: schizophrenic patients; Furn: furniture, cloth: clothes, anim: animals, flow: flowers. Error bars represented one standard error.
Figure B-6: Topographical distribution (top view, nose up) of the contrast scores for controls (top) and patients (bottom)
B.3.3 : Results - Spatio-temporal correlations
ANOVA revealed an interaction DEPTH x GROUP for earlier time intervals (090-130 ms:
F(2,36)=3.68, p<.05); all time windows between 170 and 330 ms: DEPTH x GROUP: 170-210 ms:
F(2,36)=4.20, p<.04; 210-250 ms: F(2,36)=4.36 , p<.04; 250-290 ms: F(2,36)= 13.31, p<.001;
290-330 ms: F(2,36)=4.17, p<.04). Post-hoc tests compared groups separetely for each level of the factor DEPTH. For the initial time window (90-130 ms after picture onset), groups differed in the dorsal regions (F(1,18)=6.41, p<.03) – patients showed significantly higher contrast values than control subjects (controls: 0.23 (SD: 0.61) vs. patients: 0.56 (SD: 0.76) ). Starting from 170 to 330 ms after picture onset, groups differed for the ventral region, corresponding to the ventral visual pathway (170-210 ms: F(1,18)=6.94, p<0.02; 210-250 ms: F(1,18)=3.68, p<0.08; 250-290 ms:
F(1,18)=6.72, p<0.02; 290-330 ms: F(1,18)=5.68, p<0.03). Categorization was better for the con-trol group than for the schizophrenic patients as indicated by the higher contrast scores ((170-210 ms: 0.73 (SD: 0.44) vs. 0.28 (SD: 0.30), 210-250 ms: 0.59 (SD: 0.40) vs. 0.29 (SD:0.31), 250-290 ms: 0.70 (SD: 0.36) vs. 0.33 (SD: 0.26), 290-330 ms: 0.94 (SD: 0.63) vs. 0.37 (SD: 0.40)). More-over, additional differences between groups were found during early time windows. At 90-130 ms after onset of the stimuli, a significant interaction HEMISPHERE x GROUP was evident
(F(1,18)=7.04; p<.02). Schizophrenic patients showed more right-hemispheric activity in this time window (HEMISPHERE: controls: F(1,9)<1; patients: F(1,9)=15.58, p<.01).
In the following time window (130-170 ms), a main effect GROUP (F(1,18)=6.35; p<.02) was evi-dent. Controls showed higher contrast scores during this time window than patients did (Controls:
0.59 (SD: 0.92); Patients: 0.27 (SD: 0.74)).
B.3.4 : Results - Hierarchical clustering
B.3.4 Hierarchical clustering
Unsupervised hierarchical clustering was performed separately for the left and right hemisphere.
Results for the two hemispheres, separated by group, are illustrated in Figure B-7 for the time win-dow from the 210-450 ms after picture onset.
For controls, hierarchical clustering (based on the left hemispheric data) after 12 passes resulted in 80
Figure B-7: Dynamic process of unsupervised hierarchical clustering of the data averaged between 210-450 ms over the left (left panel) and right hemisphere (right panel) for controls (top) and patients (bottom). For illustration, each base-level concept was assigned a sequential number from 1 to 16. Each column matrix represents the ad-hoc clustering at each pass.
This process starts with 16 different vectors and ends with one collapsed cluster. Shaded cells highlight the online clustering of base-level concepts within one super-ordinate category.
B.3.4 : Results - Hierarchical clustering
the original, a priori categories. For the right hemisphere, some misclassifications appeared, but the initial 6 passes all yielded within category combinations. For patients, though over the right hemi-sphere one of the categories was clustered by the algorithm after 12 passes, overall clustering was less good and categories were less organized. Furthermore, it is noteworthy that over both hemi-spheres, already the first pass resulted in the combination of objects from two different categories.
To quantify the goodness of the hierarchical clustering and to follow it's time course, hemisphere-wise uncertainty coefficients were computed for each group and time windows of 40 ms length. The results are displayed in Figure B-8.
The better defined clustering in controls is reflected in higher coefficients for the control group starting at about 210 ms after the stimuli were presented. For both groups, there was a tendency for better clustering in the left hemisphere.
Figure B-8: Uncertainty coefficients for the hierarchical clustering process for both hemispheres and groups. Blue:
controls, red: patients, dashed lines: left hemisphere, solid lines: right hemisphere.
B.3.5 : Results - Self-organizing semantic mapping (SOM)