D2-Like Receptor Expression in the Hippocampus and Amygdala Informs Performance on the Stop-Signal Task in Parkinson's Disease

Leah G. Mann; Kaitlyn R. Hay; Alexander K. Song; Steven P. Errington; Paula Trujillo; David H. Zald; Yan Yan; Hakmook Kang; Gordon D. Logan; Daniel O. Claassen

doi:10.1523/JNEUROSCI.0968-21.2021

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Figure 1.
Group results for the stop-signal task variables. A, Placebo SSRT did not significantly differ between patients with ICBs and patients without ICBs. B, Placebo GoRT did not significantly differ between patients with ICBs and patients without ICBs.
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Figure 2.
Voxel-wise regression of baseline [¹⁸F]fallypride BP_ND on placebo SSRT. A, Map of significant clusters where SSRT was negatively correlated with [¹⁸F]fallypride BP_ND in PD patients, overlaid on coronal and axial slices of an MNI template brain. All survived cluster-level FDR correction at p < 0.05. Areas include the amygdala, hippocampus, and left orbitofrontal cortex. Brains are displayed according to radiologic convention, with the left side of the brain shown on the right side of the image. B, Regions showing significance for a negative correlation between [¹⁸F]fallypride BP_ND and SSRT.
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Figure 3.
Scatterplots with lines of best fit displaying the relationship between placebo SSRT and baseline [¹⁸F]fallypride BP_ND. A GLM was applied with SSRT as the dependent variable and mean ROI BP_ND as the independent variable. Age and sex served as covariates. A significant negative correlation between BP_ND and SSRT was observed for the (A) amygdala (p = 0.005) and (B) hippocampus (p = 0.007), indicating a negative relationship between D_2/3 expression and stopping control in these limbic areas.
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Figure 4.
Scatterplot with line of best fit displaying the relationship between SSRT change (SSRT placebo – SSRT dAMPH) and baseline [¹⁸F]fallypride BP_ND. A GLM was applied with SSRT change as the dependent variable and mean ROI BP_ND as the independent variable. Age and sex served as covariates. A negative correlation between BP_ND and SSRT change was observed for the hippocampus (p = 0.045), but it did not survive FDR correction for multiple comparisons at 0.05.

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Table 1.

Demographic and clinical evaluation of the PD participants

Variables	All PD patients	ICB patients	Non-ICB patients	p value
N	17	8	9	--
Sex (M/F)	11/6	4/4	7/2	0.231^{^a}
Age (years)	64.2 ± 6	62.4 ± 4.5	65.8 ± 7	0.330^{^b}
Disease duration (years)	5.8 ± 3.5	5.7 ± 3.3	5.9 ± 3.8	0.689^{^b}
CES-D	15.3 ± 10.7	16.9 ± 6.9	14.1 ± 13.2	0.182^{^b}
MDS-UPDRS-II	13.6 ± 9.2	17.3 ± 9.6	10.4 ± 8.1	0.197^{^b}
MDS-UPDRS-III (off)	28.8 ± 12.5	28.4 ± 13.7	29.1 ± 12.1	0.833^{^b}
Total LEDD (mg/d)	680.6 ± 310	688.1 ± 315.4	673.9 ± 324.1	0.986^{^b}
Agonist single dose equivalent (mg/d)	75.3 ± 31.5	79.3 ± 32.5	72.2 ± 32.3	0.620^{^b}
QUIP-RS	23.6 ± 13.3	29.8 ± 13.2	18.1 ± 11.3	0.108^{^b}

Data are shown as mean ± SD.
CES-D: Center for Epidemiologic Studies Depression Scale.
MDS-UPDRS: Movement Disorders Society-United Parkinson's Disease Rating Scale.
LEDD: levodopa equivalent daily dose.
QUIP-RS: Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale.
↵^ap value from χ² test between ICB and non-ICB patients.
↵^bp value from Wilcoxon rank-sum test between ICB and non-ICB patients.

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Table 2.

Stop-signal task performance following placebo administration

	All PD patients (n = 17)	ICB patients	Non-ICB patients	p value
SSRT (ms)	273.84 ± 35.10	260.84 ± 34.05	285.39 ± 33.62	0.167
GoRT (ms)	599.59 ± 106.04	604.86 ± 134.90	594.91 ± 80.72	0.888
Trigger failures (percentage)	5.67 ± 8.73	5.44 ± 10.09	5.86 ± 7.95	0.384

Data are shown as mean ± SD.
p values from Wilcoxon rank-sum test between ICB and non-ICB patients.

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Table 3.

[¹⁸F]Fallypride BP_ND (baseline) effects on SSRT

ROI	[¹⁸F]fallypride BP_ND Mean ± SD	SSRT ∼ BP_ND + age + sex
ROI	[¹⁸F]fallypride BP_ND Mean ± SD	95% CI	Coefficient	p value^{^a}
Ventral striatum	15.15 ± 2.68	[−15.131, 2.478]	−6.33	0.145
Caudate	16.69 ± 2.35	[−16.140, 5.264]	−5.44	0.292
Putamen	22.37 ± 3.55	[−9.766, 6.030]	−1.87	0.618
Substantia nigra	1.23 ± 0.26	[−132.333, 5.466]	−63.43	0.068
Globus pallidus	10.14 ± 1.84	[−16.358, 7.822]	−4.27	0.459
Amygdala	2.18 ± 0.54	[−78.796, −17.734]	−48.26	0.005^{^b}
Hypothalamus	2.64 ± 0.43	[−96.176, 18.600]	−38.79	0.168
Thalamus	1.75 ± 0.37	[−103.651, 20.669]	−41.49	0.173
Hippocampus	0.98 ± 0.27	[−175.101, −34.775]	−104.94	0.007^{^b}
Insula	2.13 ± 0.79	[−38.278, 22.924]	−7.68	0.597
Ventromedial orbitofrontal Cortex	4.16 ± 1.73	[−21.157, 2.239]	−9.46	0.104
Anterior cingulate cortex	0.20 ± 0.12	[−266.992, 45.958]	−110.52	0.151