Long-Term Test–Retest Reliability of Striatal and Extrastriatal Dopamine D<sub>2/3</sub> Receptor Binding: Study with [<sup>11</sup>C]Raclopride and High-Resolution PET

Alakurtti, Kati; Johansson, Jarkko; Joutsa, Juho; Laine, Matti; Bäckman, Lars; Nyberg, Lars; Rinne, Juha O.

doi:10.1038/jcbfm.2015.53

Cited by 88 publications

(87 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This finding is consistent with observations in previous PETimaging studies with a high-affinity D2 ligand (22,23). Although extrastriatal D2DR availability has been detected previously with [ 11 C]raclopride (36,37) and with relatively high reliability (38), this low-affinity ligand is not optimal for imaging of extrastriatal BP ND . However, the reported D2DR BP ND values for the hippocampus were in the expected range [5-10% of caudate levels (13)], and the signal was positive and significantly higher compared with the receptor-free cerebellar region.…”

Section: Discussionsupporting

confidence: 91%

Dopamine D2 receptor availability is linked to hippocampal–caudate functional connectivity and episodic memory

Nyberg

Karalija

Salami

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

144

131

View full text Add to dashboard Cite

D1 and D2 dopamine receptors (D1DRs and D2DRs) may contribute differently to various aspects of memory and cognition. The D1DR system has been linked to functions supported by the prefrontal cortex. By contrast, the role of the D2DR system is less clear, although it has been hypothesized that D2DRs make a specific contribution to hippocampus-based cognitive functions. Here we present results from 181 healthy adults between 64 and 68 y of age who underwent comprehensive assessment of episodic memory, working memory, and processing speed, along with MRI and D2DR assessment with [ 11 C]raclopride and PET. Caudate D2DR availability was positively associated with episodic memory but not with working memory or speed. Whole-brain analyses further revealed a relation between hippocampal D2DR availability and episodic memory. Hippocampal and caudate D2DR availability were interrelated, and functional MRIbased resting-state functional connectivity between the ventral caudate and medial temporal cortex increased as a function of caudate D2DR availability. Collectively, these findings indicate that D2DRs make a specific contribution to hippocampus-based cognition by influencing striatal and hippocampal regions, and their interactions.dopamine | memory | hippocampus D opamine (DA) plays a key role in several cognitive processes (1-4). Reductions of D1 and D2 DA receptors (D1DRs and D2DRs) in aging (5-7) have been linked to agerelated cognitive deficits (8, 9). The D1DR system has been related to functions supported by the prefrontal cortex (PFC), such as working memory and executive functions (10-12), which may reflect the relatively high density of D1DRs in the PFC (13). However, the role of D2DRs is far less clear. D2DRs are present in the PFC at very low densities (13), and evidence supporting a role for the D2DR system in working memory and executive functions is elusive (10). Pharmacological (14, 15) and PET studies assessing striatal D2DR availability (or binding potential to nondisplacable tissue uptake; BP ND ) with [ 11 C]raclopride (16, 17) have yielded mixed findings in relation to cognition. It has been hypothesized that D2DRs make a specific contribution to hippocampus-based cognitive functions (10,18,19). Supporting these claims, positive links between D2DR BP ND and episodic memory are commonly observed (20-23). PET imaging of hippocampal D2DR BP ND also provides support for this hypothesis, although some studies indicate that hippocampal D2DRs may be related to both episodic memory and PFC-based executive functions (22, 23), including verbal working memory (24). Medial temporal lobe regions have been implicated in working memory (25,26), and D2DR-mediated modulation may be exerted via hippocampal-cortical pathways (27). In addition, a [ 11 C]raclopride task-activation PET study demonstrated contributions of striatal D2DRs to a verbal working-memory task (11).Taken together, the specific role of the D2DR system in cognition remains unclear, likely due to the fact that past studies included small and age-hetero...

show abstract

Section: Discussionsupporting

confidence: 91%

Dopamine D2 receptor availability is linked to hippocampal–caudate functional connectivity and episodic memory

Nyberg

Karalija

Salami

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

144

131

View full text Add to dashboard Cite

show abstract

“…The reliability of our data was lower in extrastriatal regions compared to 292 striatum ( Table 2). We were not able to replicate the VAR values of 3.7-13.1% or ICC of 293 0.64-0.92 in the extrastriatal regions reported by Alakurtti et al (2015). Further, it should 294 be noted that before validity is proven it is difficult to interpret ICC and VAR, or rather: 295 poor values still indicate a problem even if the validity is good, but before accepting a 296 high ICC or low VAR as indicative of reliable specific binding, validity need to be 297 established.…”

contrasting

confidence: 69%

Validity and reliability of extrastriatal [¹¹C]raclopride binding quantification in the living human brain

Svensson

Schain

Plavén-Sigray

et al. 2019

Preprint

View full text Add to dashboard Cite

35[ 11 C]raclopride is a well established PET tracer for the quantification of dopamine 2/3 36 receptors (D2/3R) in the striatum. Outside of the striatum the receptor density is up to two 37 orders of magnitude lower. In contrast to striatal binding, the characteristics of 38 extrastriatal [ 11 C]raclopride binding quantification has not been thoroughly described. 39Still, binding data for e.g., neocortex is frequently reported in the scientific literature. 40Here we evaluate the validity and reliability of extrastriatal [ 11 C]raclopride binding 41 quantification. Two sets of healthy control subjects were examined with HRRT and 42[ 11 C]raclopride: i) To assess the validity of extrastriatal [ 11 C]raclopride binding estimates, 43 eleven subjects were examined at baseline and after dosing with quetiapine, a D2/3R 44 antagonist. ii) To assess test-retest repeatability, nine subjects were examined twice. Non 45 displaceable binding potential (BPND) was quantified using the simplified reference tissue 46 model. Quetiapine dosing was associated with decrease in [ 11 C]raclopride BPND in 47 temporal cortex (18±17% occupancy) and thalamus (20±17%), but not in frontal cortex. 48Extrastriatal occupancy was lower than in putamen (51±4%). The mean absolute 49 variation was 4-7% in the striatal regions, 17% in thalamus, and 13-59% in cortical 50 regions. Our data indicate that [ 11 C]raclopride PET is not a suitable tool for D2/3R binding 51 quantification in extrastriatal regions. 52 Keywords: dopamine, extrastriatal, positron emission tomography, 53 raclopride, reference region 54 55 56

show abstract

“…In humans, D2 receptor density is low in PFC, moderate in amygdala, and highest in striatum (Kessler et al, 1993). However, despite diffuse PFC receptors, [ 11 C]raclo-pride test-retest in ACC demonstrates high reliability (intraclass correlation ϭ 0.84) following 5 weeks, comparable to reliability in striatum (0.82-0.83; Alakurtti et al, 2015). Using [ 11 C]raclopride, this study takes initial steps to describe relationships between individual differences in neurochemistry, correlated fMRI activity, and normal variation in trait anxiety.…”

Section: Introductionmentioning

confidence: 99%

Dopaminergic Mechanisms Underlying Normal Variation in Trait Anxiety

et al. 2019

View full text Add to dashboard Cite

Trait anxiety has been associated with altered activity within corticolimbic pathways connecting the amygdala and rostral anterior cingulate cortex (rACC), which receive rich dopaminergic input. Though the popular culture uses the term "chemical imbalance" to describe the pathophysiology of psychiatric conditions such as anxiety disorders, we know little about how individual differences in human dopamine neurochemistry are related to variation in anxiety and activity within corticolimbic circuits. We addressed this issue by examining interindividual variability in dopamine release at rest using [ 11 C]raclopride positron emission tomography (PET), functional connectivity between amygdala and rACC using resting-state functional magnetic resonance imaging (fMRI), and trait anxiety measures in healthy adult male and female humans. To measure endogenous dopamine release, we collected two [ 11 C]raclopride PET scans per participant. We contrasted baseline [ 11 C]raclopride D2/3 receptor binding and D2/3 receptor binding following oral methylphenidate administration. Methylphenidate blocks the dopamine transporter, which increases extracellular dopamine and leads to reduced [ 11 C]raclopride D2/3 receptor binding via competitive displacement. We found that individuals with higher dopamine release in the amygdala and rACC self-reported lower trait anxiety. Lower trait anxiety was also associated with reduced rACC-amygdala functional connectivity at baseline. Further, functional connectivity showed a modest negative relationship with dopamine release such that reduced rACC-amygdala functional connectivity was accompanied by higher levels of dopamine release in these regions. Together, these findings contribute to hypodopaminergic models of anxiety and support the utility of combining fMRI and PET measures of neurochemical function to advance our understanding of basic affective processes in humans.It is common wisdom that individuals vary in their baseline levels of anxiety. We all have a friend or colleague we know to be more "tightly wound" than others, or, perhaps, we are the ones marveling at others' ability to "just go with the flow." Although such observations about individual differences within nonclinical populations are commonplace, the neural mechanisms underlying normal variation in trait anxiety have not been established. Using multimodal brain imaging in humans, this study takes initial steps in linking intrinsic measures of neuromodulator release and functional connectivity within regions implicated in anxiety disorders. Our findings suggest that in healthy adults, higher levels of trait anxiety may arise, at least in part, from reduced dopamine neurotransmission.

show abstract

Long-Term Test–Retest Reliability of Striatal and Extrastriatal Dopamine D_2/3 Receptor Binding: Study with [¹¹C]Raclopride and High-Resolution PET

Cited by 88 publications

References 38 publications

Dopamine D2 receptor availability is linked to hippocampal–caudate functional connectivity and episodic memory

Dopamine D2 receptor availability is linked to hippocampal–caudate functional connectivity and episodic memory

Validity and reliability of extrastriatal [¹¹C]raclopride binding quantification in the living human brain

Dopaminergic Mechanisms Underlying Normal Variation in Trait Anxiety

Contact Info

Product

Resources

About

Long-Term Test–Retest Reliability of Striatal and Extrastriatal Dopamine D2/3 Receptor Binding: Study with [11C]Raclopride and High-Resolution PET

Cited by 88 publications

References 38 publications

Dopamine D2 receptor availability is linked to hippocampal–caudate functional connectivity and episodic memory

Dopamine D2 receptor availability is linked to hippocampal–caudate functional connectivity and episodic memory

Validity and reliability of extrastriatal [11C]raclopride binding quantification in the living human brain

Dopaminergic Mechanisms Underlying Normal Variation in Trait Anxiety

Contact Info

Product

Resources

About

Long-Term Test–Retest Reliability of Striatal and Extrastriatal Dopamine D_2/3 Receptor Binding: Study with [¹¹C]Raclopride and High-Resolution PET

Validity and reliability of extrastriatal [¹¹C]raclopride binding quantification in the living human brain