Article Figures & Data
Figures
- Figure 1.
Validation of the AAV-α-synuclein model. A) Cylinder test of the animals showing the ratio of touches by the contralateral paw to the total number of touches. The control animals (in black) have a ratio of 0.51 indicating equal use of both paws. The α-synuclein animals (in grey), have a ratio of 0.35 indicating that they use the paw contralateral of the injection less than the ipsilateral paw. (B-G) Representative coronal sections stained for α-synuclein. B) 40x magnification of striatal neurons showing α-synuclein-positive inclusions. C) 2,5x magnification of striatum showing α-synuclein immunoreactivity. D) 2,5x magnification of striatum contralateral to the injection of AAV-α-synuclein. E) 40x magnification showing α-synuclein in cell somas in the substantia nigra. F) 2,5x magnification of section showing the substantia nigra and the superior colliculus. G) 40x magnification showing α-synuclein immunoreactivity in the SC. The slices were stained with 4B12 (human WT alpha-synuclein).
- Figure 2.
Statistical group maps of BOLD fMRI responses to visual stimulation. The colour bar shows the thresholds for the z-scores, as anything between -2 and 2 is considered insignificant. The figure shows the group averages of activation as computed in the level 3 FEAT analysis and registered to a high-resolution anatomical scan. A) control group B) α-synuclein group. Visual stimulation with flickering light robustly activated the superior colliculus (SC) and in the visual cortex (VC). Additionally, the paraflocculus/flocculus complex (Pfl/Fl) was activated.
- Figure 3.
Estimation statistics of percent change in BOLD during 1 Hz stimulation. The top panel shows the data points from each ROI. OB of control group (blue), OB of α-synuclein group (yellow), VC of control group (green and red), VC of α-synuclein group (purple and brown), SC of control group (pink and grey), SC of α-synuclein group (chartreuse and turquois). The ROI as designated as contra- (contralateral) or ipsi- (ipsilateral) relative to the injection and expression of α-synuclein. The lower panel shows the difference of response when the response of the olfactory bulb in the control group is subtracted from each ROI. BOLD responses from both the VC and SC differs significantly from the olfactory bulb. Asterisks refer to difference from control of p>0.05=not significant (ns), *p<0.05, **p<0.01, and ***p<0.001.
- Figure 4.
Estimation statistics of percent change in BOLD during 14 Hz. The top panel shows the data points from each ROI. OB of control group (blue), OB of α-synuclein group (yellow), VC of control group (green and red), VC of α-synuclein group (purple and brown), SC of control group (pink and grey), SC of α-synuclein group (chartreuse and turquois). The lower panel shows the difference of response when the response of the olfactory bulb in the control group is subtracted from each ROI. Responses from the SC differ significantly from OB. As does the contralateral VC from control group along with the response from the ipsilateral to the injection in the α-synuclein group. Asterisks refer to difference from control of p>0.05=not significant (ns), *p<0.05, **p<0.01, and ***p<0.001.
- Figure 5.
Comparison of differences within animals as paired. Right and left hemisphere from the control group, are shown on the left, and for the α-synuclein group on the right. The lower panel shows the estimated mean difference between hemispheres within the groups. The statistics does not reveal any asymmetry induced by expression of human α-synuclein.
Tables
Figure Stimulus Control ROI ROI Effect size CI (width 95.0%) p value Lower bound Upper bound 3 1 Hz OB control OB α-synuclein −0.000905 −0.00444 0.0502 0.981 VC control contra- 0.493 0.344 0.651 0.00022 VC control ipsi- 0.415 0.255 0.568 0.00099 VC α-synuclein contra- 0.336 −0.0667 0.609 0.0452 VC α-synuclein ipsi- 0.429 0.127 0.68 0.0044 SC control contra- 1.2 0.885 1.52 0.000123 SC control ipsi- 1.15 0.816 1.57 0.000498 SC α-synuclein contra- 1.28 0.917 1.5 0.000133 SC α-synuclein ipsi- 1.22 0.958 1.4 0.000036 4 14 Hz OB control OB α-synuclein −0.038 −0.243 0.14 0.722 VC control contra- −0.424 −0.785 −0.0208 0.0496 VC control ipsi- −0.257 −0.528 0.0135 0.0926 VC α-synuclein contra- −0.258 −0.638 0.0227 0.139 VC α-synuclein ipsi- −0.414 −0.714 −0.182 0.0012 SC control contra- 1.29 0.744 1.8 0.0006 SC control ipsi- 1.22 0.66 1.9 0.0006 SC α-synuclein contra- 1.38 0.585 2.01 0.001 SC α-synuclein ipsi- 1.21 0.273 1.72 0.0026 The 95 % CI are based on a two-sided permutation t-test with 5000 bootstraps. ROI; region of interest, Contra-; contralateral to the injection, Ipsi-; ipsilateral to the injection, OB; olfactory bulb, VC; visual cortex, SC; superior colliculus.
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