Figure e-1 Correlation between baseline CAMCOG and whole-brain synchronization likelihood values. CAMCOG: Cambridge cognition, CTRL: controls, PD: Parkinson’s disease patients.


Table e-1 Cognitive, UPDRS-III and CAMCOG (sub)scores

Baseline / Follow up / Longitudinal / Baseline / Follow up
Mean / SD / Mean / SD / p / p / p
Controls
Semantic fluency / 24.00 / 4.658 / 24.58 / 6.501 / 1.000
PRM correct responses / 22.36 / 1.69 / 22.83 / 1.03 / 0.613
SSP span length / 5.571 / 1.089 / 5.583 / 0.900 / 0.776
SWM between errors / 23.214 / 13.571 / 19.667 / 14.164 / 0.881
IED stages / 8.769 / 0.599 / 8.500 / 0.905 / 0.491
VPT redundancy / 19.577 / 4.470 / 17.928 / 2.446 / 0.958
CAMCOG subscales:
Orientation / 9.714 / 0.469 / 9.583 / 0.669 / 0.275
Language / 28.500 / 0.760 / 28.667 / 0.985 / 0.191
Memory / 24.500 / 1.225 / 24.583 / 1.676 / 0.862
Attention / 4.000 / 0.000 / 4.000 / 0.000 / 1.000
Praxis / 11.857 / 0.535 / 11.583 / 0.669 / 0.275
Calculation / 4.857 / 0.363 / 4.417 / 0.793 / 0.017
Abstract thinking / 6.929 / 1.072 / 7.417 / 0.793 / 0.039
Perception / 10.857 / 0.363 / 10.750 / 0.452 / 0.586
Patients
Semantic fluency / 19.982 / 6.704 / 19.472 / 7.327 / 0.096 / 0.090 / 0.058
PRM correct responses / 20.778 / 2.745 / 20.943 / 2.786 / 0.219 / 0.238 / 0.054
SSP span length / 4.852 / 1.035 / 4.514 / 1.095 / 0.021 / 0.029 / 0.006
SWM between errors / 38.655 / 22.303 / 41.543 / 22.621 / 0.198 / 0.003 / 0.003
IED stages / 7.436 / 2.616 / 6.853 / 2.851 / 0.070 / 0.234 / 0.096
VPT redundancy / 25.387 / 10.036 / 25.713 / 13.312 / 0.876 / 0.040 / 0.114
UPDRS-III subscales:
UPDRS: tremor / 1.818 / 2.010 / 3.300 / 8.890 / 0.275 / 0.042 / 0.377
UPDRS: bradykinesia / 11.600 / 5.779 / 18.240 / 9.950 / <0.001 / <0.001 / <0.001
UPDRS: PIGD / 3.091 / 1.590 / 4.280 / 5.111 / 0.107 / <0.001 / 0.045
CAMCOG subscales:
Orientation / 9.600 / 0.894 / 9.400 / 1.439 / 0.193 / 0.978 / 0.879
Language / 27.418 / 2.097 / 26.857 / 3.972 / 0.194 / 0.257 / 0.304
Memory / 22.618 / 2.430 / 22.314 / 3.332 / 0.113 / 0.050 / 0.082
Attention / 3.873 / 0.511 / 3.686 / 0.832 / 0.083 / 0.720 / 0.288
Praxis / 11.145 / 1.283 / 10.800 / 1.982 / 0.018 / 0.170 / 0.292
Calculation / 4.473 / 0.997 / 4.257 / 1.336 / 0.091 / 0.318 / 0.805
Abstract thinking / 6.600 / 1.606 / 6.400 / 1.631 / 0.433 / 0.575 / 0.118
Perception / 10.091 / 0.967 / 9.314 / 1.568 / 0.006 / 0.053 / 0.012

SD: standard deviation, PRM: Pattern recognition memory, SSP: Spatial span, SWM: Spatial working memory, IED: Intra-extra dimensional set shift, VPT: Vienna perserveration test, UPDRS: Unified Parkinson’s disease rating scale, PIGD: Postural instability and gait disorder, CAMCOG: Cambridge cognition. Bold indicates statistical significance.

Table e-2Brain regions having lower functional connectivity (synchronization likelihood, SL) values in PD patients compared to control subjects (cross-sectional analysis).

Brain region (bilateral) / SL value controls (n = 15) / SL value PD
(n = 55) / p-value#
Gyrus rectus / 0.127 (0.028) / 0.110 (0.016) / .003
Olfactory cortex / 0.124 (0.015) / 0.121 (0.018) / n/s
Superior frontal gyrus, orbital part / 0.148 (0.039) / 0.123 (0.021) / .002
Superior frontal gyrus, medial orbital part / 0.145 (0.035) / 0.123 (0.019) / .002
Middle frontal gyrus, orbital part / 0.150 (0.050) / 0.121 (0.018) / .0008
Inferior frontal gyrus, orbital part / 0.162 (0.047) / 0.138 (0.024) / .008
Superior frontal gyrus, dorsolateral part / 0.163 (0.054) / 0.142 (0.029) / .045
Middle frontal gyrus / 0.166 (0.060) / 0.141 (0.030) / .025
Inferior frontal gyrus, opercular part / 0.169 (0.058) / 0.141 (0.032) / .019
Inferior frontal gyrus, triangular part / 0.162 (0.056) / 0.140 (0.031) / .045
Superior frontal gyrus, medial part / 0.156 (0.054) / 0.138 (0.028) / n/s
Supplementary motor area / 0.165 (0.049) / 0.143 (0.030) / .032
Paracentral lobule / 0.160 (0.050) / 0.133 (0.025) / .004
Precentral gyrus / 0.179 (0.053) / 0.142 (0.030) / .0008
Rolandic operculum / 0.187 (0.053) / 0.153 (0.030) / .002
Postcentral gyrus / 0.176 (0.054) / 0.141 (0.028) / .0009
Superior parietal gyrus / 0.166 (0.057) / 0.133 (0.025) / .002
Inferior parietal gyrus / 0.154 (0.054) / 0.128 (0.027) / .010
Supramarginal gyrus / 0.165 (0.059) / 0.137 (0.032) / .016
Angular gyrus / 0.140 (0.054) / 0.121 (0.027) / n/s
Precuneus / 0.168 (0.056) / 0.146 (0.033) / n/s
Superior occipital gyrus / 0.172 (0.050) / 0.138 (0.028) / .001
Middle occipital gyrus / 0.180 (0.055) / 0.140 (0.029) / .0004
Inferior occipital gyrus / 0.170 (0.041) / 0.139 (0.025) / .0005
Calcarine cortex / 0.184 (0.045) / 0.149 (0.030) / .0008
Cuneus / 0.177 (0.055) / 0.140 (0.028) / .0006
Lingual gyrus / 0.187 (0.038) / 0.153 (0.029) / .0003
Fusiform gyrus / 0.183 (0.043) / 0.150 (0.028) / .0008
Heschl’s gyrus / 0.170 (0.038) / 0.148 (0.029) / .015
Superior temporal gyrus / 0.195 (0.058) / 0.154 (0.033) / .0007
Middle temporal gyrus / 0.182 (0.053) / 0.142 (0.030) / .0003
Inferior temporal gyrus / 0.166 (0.050) / 0.140 (0.024) / .006
Temporal pole: superior temporal gyrus / 0.155 (0.029) / 0.137 (0.021) / .009
Temporal pole: middle temporal gyrus / 0.133 (0.031) / 0.118 (0.020) / .028
Parahippocampal gyrus / 0.153 (0.026) / 0.136 (0.020) / .011
Anterior (para)cingulate gyrus / 0.159 (0.032) / 0.140 (0.026) / .022
Median (para)cingulate gyrus / 0.174 (0.056) / 0.149 (0.031) / .027
Posterior cingulate gyrus / 0.137 (0.035) / 0.128 (0.025) / n/s
Insula / 0.180 (0.044) / 0.153 (0.030) / .008
Thalamus / 0.175 (0.044) / 0.150 (0.030) / .012
Caudate nucleus / 0.166 (0.058) / 0.133 (0.027) / .002
Putamen / 0.156 (0.046) / 0.129 (0.028) / .006
Globus pallidus / 0.145 (0.040) / 0.122 (0.020) / .003
Hippocampus / 0.158 (0.038) / 0.138 (0.024) / .013
Amygdala / 0.136 (0.037) / 0.119 (0.018) / .011
Nucleus accumbens / 0.123 (0.028) / 0.111 (0.017) / n/s

SL values are expressed as mean (SD). # independent-samples t-testin which significant effects

are displayed in bold (FDR controlled) and remaining effects with p < .05 a trend; n/s, non-

significant

Table e-3Brain regions showing a decrease in functional connectivity (synchronization likelihood, SL) values in PD patients (n = 36) over time (longitudinal analysis).

Brain region (bilateral) / SL value
time point 1 / SL value
time point 2 / p-value#
Gyrus rectus / 0.108 (0.014) / 0.112 (0.023) / n/s
Olfactory cortex / 0.121 (0.019) / 0.120 (0.017) / n/s
Superior frontal gyrus, orbital part / 0.122 (0.018) / 0.116 (0.023) / n/s
Superior frontal gyrus, medial orbital part / 0.122 (0.018) / 0.121 (0.017) / n/s
Middle frontal gyrus, orbital part / 0.120 (0.016) / 0.118 (0.025) / n/s
Inferior frontal gyrus, orbital part / 0.136 (0.021) / 0.127 (0.021) / .035
Superior frontal gyrus, dorsolateral part / 0.142 (0.025) / 0.133 (0.029) / n/s
Middle frontal gyrus / 0.140 (0.027) / 0.133 (0.031) / n/s
Inferior frontal gyrus, opercular part / 0.139 (0.028) / 0.133 (0.032) / n/s
Inferior frontal gyrus, triangular part / 0.138 (0.025) / 0.131 (0.028) / n/s
Superior frontal gyrus, medial part / 0.138 (0.024) / 0.133 (0.028) / n/s
Supplementary motor area / 0.143 (0.026) / 0.130 (0.026) / .011
Paracentral lobule / 0.134 (0.023) / 0.119 (0.031) / .005
Precentral gyrus / 0.143 (0.025) / 0.132 (0.028) / .039
Rolandic operculum / 0.155 (0.026) / 0.146 (0.028) / n/s
Postcentral gyrus / 0.141 (0.023) / 0.131 (0.026) / .033
Superior parietal gyrus / 0.133 (0.020) / 0.122 (0.029) / .028
Inferior parietal gyrus / 0.126 (0.019) / 0.121 (0.026) / n/s
Supramarginal gyrus / 0.135 (0.024) / 0.126 (0.026) / n/s
Angular gyrus / 0.118 (0.022) / 0.115 (0.025) / n/s
Precuneus / 0.146 (0.029) / 0.136 (0.032) / n/s
Superior occipital gyrus / 0.137 (0.023) / 0.125 (0.029) / .013
Middle occipital gyrus / 0.139 (0.023) / 0.124 (0.031) / .005
Inferior occipital gyrus / 0.138 (0.022) / 0.127 (0.030) / .036
Calcarine cortex / 0.149 (0.027) / 0.137 (0.027) / .012
Cuneus / 0.140 (0.024) / 0.130 (0.029) / .044
Lingual gyrus / 0.152 (0.027) / 0.143 (0.031) / n/s
Fusiform gyrus / 0.150 (0.025) / 0.140 (0.031) / n/s
Heschl’s gyrus / 0.150 (0.025) / 0.141 (0.026) / n/s
Superior temporal gyrus / 0.155 (0.027) / 0.142 (0.031) / .019
Middle temporal gyrus / 0.140 (0.024) / 0.132 (0.032) / n/s
Inferior temporal gyrus / 0.139 (0.022) / 0.127 (0.028) / n/s
Temporal pole: superior temporal gyrus / 0.138 (0.020) / 0.131 (0.019) / n/s
Temporal pole: middle temporal gyrus / 0.117 (0.019) / 0.110 (0.017) / n/s
Parahippocampal gyrus / 0.137 (0.019) / 0.132 (0.023) / n/s
Anterior (para)cingulate gyrus / 0.141 (0.025) / 0.141 (0.021) / n/s
Median (para)cingulate gyrus / 0.150 (0.027) / 0.137 (0.032) / .043
Posterior cingulate gyrus / 0.126 (0.020) / 0.120 (0.028) / n/s
Insula / 0.155 (0.026) / 0.148 (0.028) / n/s
Thalamus / 0.149 (0.028) / 0.143 (0.032) / n/s
Caudate nucleus / 0.132 (0.025) / 0.129 (0.029) / n/s
Putamen / 0.128 (0.027) / 0.121 (0.025) / n/s
Globus pallidus / 0.120 (0.017) / 0.115 (0.021) / n/s
Hippocampus / 0.137 (0.022) / 0.130 (0.024) / n/s
Amygdala / 0.118 (0.017) / 0.116 (0.021) / n/s
Nucleus accumbens / 0.110 (0.017) / 0.109 (0.020) / n/s

SL values are expressed as mean (SD). # paired-samples t-test, in which significant effects are

displayed in bold (FDR controlled) and remaining effects with p < .05 a trend; n/s, non-

significant

Table e-4 Brain regions showing the most significant (p < 0.01) longitudinal decreases in

functional connectivity (SL) with paracentral, superior parietal, middle occipital and superior

temporal ROIs in PD patients (n = 36).

ROI (seed) / Connected brain regions / p-value
Paracentral lobe / Superior frontal gyrus, orbital part
Middle frontal gyrus
Postcentral gyrus
Superior parietal gyrus
Supramarginal gyrus
Superior occipital gyrus
Middle occipital gyrus
Inferior occipital gyrus
Calcarine cortex
Cuneus
Lingual gyrus
Fusiform gyrus
Inferior temporal gyrus / .001
.007
.004
<.001
.009
.006
<.001
<.001
<.001
.004
<.001
.006
.001
Superior parietal gyrus / Paracentral lobule
Calcarine cortex
Cuneus
Lingual gyrus / <.001
.001
.005
.009
Middle occipital gyrus / Superior frontal gyrus, medial orbital part
Paracentral lobule
Rolandic operculum
Postcentral gyrus
Precuneus
Cuneus
Lingual gyrus
Fusiform gyrus
Middle temporal gyrus
Inferior temporal gyrus
Temporal pole: superior temporal gyrus
Parahippocampal gyrus / .007
<.001
.009
.003
.006
.008
.003
.004
.002
.008
.007
.004
Superior temporal gyrus / Rolandic operculum
Heschl’s gyrus / <.001
.009