Levodopa-stimulated dopamine release in Tourette syndrome

RATIONALE: Several lines of evidence suggest that dopamine (DA)-influenced neuronal pathways may malfunction in Tourette Syndrome (TS). Some PET studies support the hypothesis of presynaptic abnormalities in levodopa uptake, dopamine synthesis, or dopamine release. OBJECTIVE: Directly test the presynaptic hypothesis using a new approach. METHODS: We used positron emission tomography (PET) and [11C]raclopride (RAC*) to measure synaptic dopamine release before and during levodopa and placebo infusions (with carbidopa) in 5neuroleptic-naïve adults with TS and 5 matched control subjects. The primary analysis examined RAC* binding potential (BPND) in predefined volumes of interest (VOIs). A secondary analysis compared BPND voxel by voxel over the entire brain. RESULTS: (1) Baseline RAC* BPND did not differ significantly between groups, though nucleus accumbens BPND was higher in TS (16%, p=0.051). (2) DA release declined from before to during infusions (p=0.014), including with placebo. (3) This decline was smaller in TS (p=0.080). (4) Levodopa’s effect on BPND differed significantly in right midbrain (p=0.002, corrected), where levodopa displaced RAC* by 59% in control subjects but increased BPND by 74% in TS subjects, and in parahippocampal gyrus (p=0.02, corrected). DISCUSSION: Our finding that a before/after RAC* design is confounded by time and/or expectation effects may have implications for other RAC* PET studies. The smaller decrease of BPND with time in TS may be attributable to impaired habituation to the scan environment. Levodopa’s opposite effect on RAC* binding in TS dopaminergic midbrain but may signify an abnormal response to dopaminergic stimulation in TS.

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Levodopa-stimulated dopamine release in Tourette syndrome

10.7287/peerj.preprints.30v1 ◽

2013 ◽

Author(s):

Kevin J Black ◽

Marilyn L. Piccirillo ◽

Jonathan M. Koller ◽

Tiffany Hseih ◽

Lei Wang ◽

...

Keyword(s):

Tourette Syndrome ◽

Dopamine Release ◽

Secondary Analysis ◽

Parahippocampal Gyrus ◽

Binding Potential ◽

Dopamine Synthesis ◽

Primary Analysis ◽

New Approach ◽

Control Subjects ◽

Positron Emission

BACKGROUND: Several lines of evidence suggest that dopamine (DA)-influenced neuronal pathways may malfunction in Tourette Syndrome (TS). A dopamine-responsive abnormality of brain function in TS could be either presynaptic or postsynaptic. Some PET studies support the hypothesis of presynaptic abnormalities in levodopa uptake, dopamine synthesis, or dopamine release. Alternatively, presynaptic dopaminergic function could be normal in TS but dopamine-sensitive abnormalities could exist in striatum, pallidum, thalamus, or cortex. METHODS: In this study we directly tested the presynaptic hypothesis using a new approach. We used positron emission tomography (PET) and [11C]raclopride (RAC*) to measure synaptic dopamine release in response to levodopa and placebo infusions (with carbidopa) in 5 neuroleptic-naïve adults with TS and 5 matched control subjects. The primary analysis examined RAC* binding potential (BPND) in predefined volumes of interest (VOIs). A secondary analysis compared BPND voxel by voxel over the entire brain. RESULTS: (1) Overall, baseline RAC* BPND did not differ significantly between groups, though nucleus accumbens BPND was higher in TS (16%, p=0.051). (2) Across regions, DA release declined from before to during infusion (p=0.014), including with placebo. (3) This decline was smaller in TS (p=0.080). (4) Levodopa’s effect on BPND differed significantly in right midbrain (p=0.002, corrected), where levodopa displaced RAC* by 59% in control subjects but increased BPND by 74% in TS subjects, and in parahippocampal gyrus (p=0.02, corrected). DISCUSSION: Our finding that a before/after RAC* design is confounded by time and/or expectation effects has implications for other RAC* PET studies. The smaller magnitude of the decrease with time in TS may be attributable to impaired habituation to the scan environment. Levodopa’s opposite effect on RAC* binding in TS dopaminergic midbrain was not predicted, but may signify an abnormal response to dopaminergic stimulation in TS. These findings invite confirmation in a larger sample.

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Levodopa-stimulated dopamine release in Tourette syndrome

10.7287/peerj.preprints.30v2 ◽

2014 ◽

Author(s):

Kevin J Black ◽

Marilyn L. Piccirillo ◽

Jonathan M. Koller ◽

Tiffany Hseih ◽

Lei Wang ◽

...

Keyword(s):

Tourette Syndrome ◽

Dopamine Release ◽

Secondary Analysis ◽

Parahippocampal Gyrus ◽

Binding Potential ◽

Dopamine Synthesis ◽

Primary Analysis ◽

New Approach ◽

Control Subjects ◽

Positron Emission

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Association of Surgical Hospitalization with Brain Amyloid Deposition

Anesthesiology ◽

10.1097/aln.0000000000003255 ◽

2020 ◽

Vol 132 (6) ◽

pp. 1407-1418 ◽

Cited By ~ 1

Author(s):

Keenan A. Walker ◽

Rebecca F. Gottesman ◽

Josef Coresh ◽

A. Richey Sharrett ◽

David S. Knopman ◽

...

Keyword(s):

Older Adults ◽

Pet Imaging ◽

Odds Ratio ◽

Reference Group ◽

Secondary Analysis ◽

Standardized Uptake Value ◽

Amyloid Deposition ◽

Long Term Effects ◽

Primary Analysis ◽

Positron Emission

Abstract Background As more older adults undergo surgery, it is critical to understand the long-term effects of surgery on brain health, particularly in relation to the development of Alzheimer’s disease. This study examined the association of surgical hospitalization with subsequent brain β-amyloid deposition in nondemented older adults. Methods The Atherosclerosis Risk in Communities–Positron Emission Tomography (ARIC–PET) study is a prospective cohort study of 346 participants without dementia who underwent florbetapir PET imaging. Active surveillance of local hospitals and annual participant contact were used to gather hospitalization and surgical information (International Classification of Disease, Ninth Revision, Clinical Modification codes) over the preceding 24-yr period. Brain amyloid measured using florbetapir PET imaging was the primary outcome. Elevated amyloid was defined as a standardized uptake value ratio of more than 1.2. Results Of the 313 participants included in this analysis (age at PET: 76.0 [SD 5.4]; 56% female), 72% had a prior hospitalization, and 50% had a prior surgical hospitalization. Elevated amyloid occurred in 87 of 156 (56%) participants with previous surgical hospitalization, compared with 45 of 87 (52%) participants who had no previous hospitalization. Participants with previous surgical hospitalizations did not show an increased odds of elevated brain amyloid (odds ratio, 1.32; 95% CI, 0.72 to 2.40; P = 0.370) after adjusting for confounders (primary analysis). Results were similar using the reference group of all participants without previous surgery (hospitalized and nonhospitalized; odds ratio, 1.58; 95% CI, 0.96 to 2.58; P = 0.070). In a prespecified secondary analysis, participants with previous surgical hospitalization did demonstrate increased odds of elevated amyloid when compared with participants hospitalized without surgery (odds ratio, 2.10; 95% CI, 1.09 to 4.05; P = 0.026). However, these results were attenuated and nonsignificant when alternative thresholds for amyloid-positive status were used. Conclusions The results do not support an association between surgical hospitalization and elevated brain amyloid. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

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Levodopa effects on [11C]raclopride binding in the resting human brain

F1000Research ◽

10.12688/f1000research.5672.1 ◽

2015 ◽

Vol 4 ◽

pp. 23 ◽

Cited By ~ 12

Author(s):

Kevin J. Black ◽

Marilyn L. Piccirillo ◽

Jonathan M. Koller ◽

Tiffany Hseih ◽

Lei Wang ◽

...

Keyword(s):

Dopamine Release ◽

Random Order ◽

Binding Potential ◽

Separate Analysis ◽

Double Blind ◽

Positron Emission ◽

Midbrain Region ◽

And Control ◽

Double Blind Crossover Study ◽

Da Release

Rationale: Synaptic dopamine (DA) release induced by amphetamine or other experimental manipulations can displace [11C]raclopride (RAC*) from dopamine D2-like receptors. We hypothesized that exogenous levodopa might increase dopamine release at striatal synapses under some conditions but not others, allowing a more naturalistic assessment of presynaptic dopaminergic function. Presynaptic dopaminergic abnormalities have been reported in Tourette syndrome (TS).Objective: Test whether levodopa induces measurable synaptic DA release in healthy people at rest, and gather pilot data in TS.Methods: This double-blind crossover study used RAC* and positron emission tomography (PET) to measure synaptic dopamine release 4 times in each of 10 carbidopa-pretreated, neuroleptic-naïve adults: before and during an infusion of levodopa on one day and placebo on another (in random order). Five subjects had TS and 5 were matched controls. RAC* binding potential (BPND) was quantified in predefined anatomical volumes of interest (VOIs). A separate analysis compared BPND voxel by voxel over the entire brain.Results: DA release declined between the first and second scan of each day (p=0.012), including on the placebo day. Levodopa did not significantly reduce striatal RAC* binding and striatal binding did not differ significantly between TS and control groups. However, levodopa’s effect on DA release differed significantly in a right midbrain region (p=0.002, corrected), where levodopa displaced RAC* by 59% in control subjects but increased BPND by 74% in TS subjects.Discussion: Decreased DA release on the second scan of the day is consistent with the few previous studies with a similar design, and may indicate habituation to study procedures. We hypothesize that mesostriatal DA neurons fire relatively little while subjects rest, possibly explaining the non-significant effect of levodopa on striatal RAC* binding. The modest sample size argues for caution in interpreting the group difference in midbrain DA release with levodopa.

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Effect of Simple Motor Performance on Regional Dopamine Release in the Striatum in Parkinson Disease Patients and Healthy Subjects: A Positron Emission Tomography Study

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-200206000-00013 ◽

2002 ◽

Vol 22 (6) ◽

pp. 746-752 ◽

Cited By ~ 43

Author(s):

Yasuomi Ouchi ◽

Etsuji Yoshikawa ◽

Masami Futatsubashi ◽

Hiroyuki Okada ◽

Tatsuo Torizuka ◽

...

Keyword(s):

Positron Emission Tomography ◽

Parkinson Disease ◽

Healthy Subjects ◽

Dopamine Release ◽

Dorsal Striatum ◽

Emission Tomography ◽

Binding Potential ◽

Healthy Group ◽

Logan Plot ◽

Positron Emission

To investigate changes in dopamine release in the striatum during motor exercise in human subjects with and without striatal dopamine denervation, eight healthy subjects and eight patients with Parkinson disease (PD) were measured during unilateral foot extension/flexion movement using positron emission tomography with [11C]raclopride. Five subjects in each group were later scanned in the resting condition. Estimation of binding potential (k3/k4) of [11C]raclopride was based on Logan plot method. Significant reductions in [11C]raclopride k3/k4 were found in the dorsal putamen contralateral to the exercise side in the healthy group and ipsilaterally in the PD group. Spearman rank correlation analysis showed that [11C]raclopride k3/k4 correlated inversely with the decrease in performance (velocity and motion range) in the dorsal putamen contralaterally in the healthy group and ipsilaterally in the PD group. These results suggest that simple but laborious motor exercise (motor stimulation) generates significant dopamine release in the dorsal striatum contralateral to the motor execution in humans. Lack of the crossed pattern and ipsilateral increase in dopamine release in the dorsal striatum during the unilateral limb movement may reflect the pathophysiology for hypokinetic and insufficient coordinating movement in PD.

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Brainstem changes in 5-HT1A receptor availability during migraine attack

Cephalalgia ◽

10.1177/0333102410385581 ◽

2010 ◽

Vol 31 (1) ◽

pp. 84-94 ◽

Cited By ~ 40

Author(s):

G Demarquay ◽

A Lothe ◽

JP Royet ◽

N Costes ◽

G Mick ◽

...

Keyword(s):

Migraine Attack ◽

Early Stage ◽

Region Of Interest ◽

Binding Potential ◽

Precentral Gyrus ◽

Individual Level ◽

Control Subjects ◽

Pet Tracer ◽

Positron Emission ◽

The Individual

Background: Among serotonin receptors, 5-HT1A receptors are implicated in the regulation of central serotoninergic tone and could be involved in the abnormal brain 5-HT turnover suspected in migraineurs. The aim of this study was to investigate 5-HT1A receptors’ availability during migraine attacks. Methods: Ten patients suffering from odor-triggered migraine attacks and 10 control subjects were investigated using positron emission tomography (PET) and [18F]MPPF PET tracer, a selective 5-HT1A antagonist. All subjects underwent calibrated olfactory stimulations prior to the PET study. Results: Four patients developed a migraine attack during the PET study. In these patients, statistical parametrical mapping and region of interest analyses showed an increased [18F]MPPF binding potential (BPND) in the pontine raphe when compared to headache-free migraineurs and control subjects. This ictal change was confirmed at the individual level in each of the four affected patients. In comparison with the headache-free migraineurs, patients with a migraine attack also showed significantly increased [18F]MPPF BPND in the left orbitofrontal cortex, precentral gyrus and temporal pole. No significant change in [18F]MPPF BPND was observed between headache-free migraineurs and controls. Conclusions: Our results emphasize the role of 5HT1A receptors in the pontine raphe nuclei during the early stage of migraine attacks.

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Direct voxel-based comparisons between grey matter shrinkage and glucose hypometabolism in chronic alcoholism

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x15611136 ◽

2016 ◽

Vol 36 (9) ◽

pp. 1625-1640 ◽

Cited By ~ 13

Author(s):

Ludivine Ritz ◽

Shailendra Segobin ◽

Coralie Lannuzel ◽

Céline Boudehent ◽

François Vabret ◽

...

Keyword(s):

Grey Matter ◽

Chronic Alcoholism ◽

Parahippocampal Gyrus ◽

Limited Attention ◽

Control Subjects ◽

Parietal Lobes ◽

Positron Emission ◽

Structural Abnormalities ◽

Global Brain ◽

Parietal Cortices

Alcoholism is associated with widespread brain structural abnormalities affecting mainly the frontocerebellar and the Papez’s circuits. Brain glucose metabolism has received limited attention, and few studies used regions of interest approach and showed reduced global brain metabolism predominantly in the frontal and parietal lobes. Even though these studies have examined the relationship between grey matter shrinkage and hypometabolism, none has performed a direct voxel-by-voxel comparison between the degrees of structural and metabolic abnormalities. Seventeen alcoholic patients and 16 control subjects underwent both structural magnetic resonance imaging and 18F-2-fluoro-deoxy-glucose-positron emission tomography examinations. Structural abnormalities and hypometabolism were examined in alcoholic patients compared with control subjects using two-sample t-tests. Then, these two patterns of brain damage were directly compared with a paired t-test. Compared to controls, alcoholic patients had grey matter shrinkage and hypometabolism in the fronto-cerebellar circuit and several nodes of Papez’s circuit. The direct comparison revealed greater shrinkage than hypometabolism in the cerebellum, cingulate cortex, thalamus and hippocampus and parahippocampal gyrus. Conversely, hypometabolism was more severe than shrinkage in the dorsolateral, premotor and parietal cortices. The distinct profiles of abnormalities found within the Papez’s circuit, the fronto-cerebellar circuit and the parietal gyrus in chronic alcoholism suggest the involvement of different pathological mechanisms.

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Density of available striatal dopamine receptors predicts trait impulsiveness during performance of an attention-demanding task

Journal of Neurophysiology ◽

10.1152/jn.00125.2017 ◽

2017 ◽

Vol 118 (1) ◽

pp. 64-68 ◽

Cited By ~ 4

Author(s):

Brian A. Anderson ◽

Hiroto Kuwabara ◽

Dean F. Wong ◽

Susan M. Courtney

Keyword(s):

Dopamine Receptors ◽

Resting State ◽

Dopamine Release ◽

Cognitive Task ◽

Binding Potential ◽

Receptor Density ◽

Data Set ◽

Positron Emission ◽

Context Dependent ◽

The Individual

The density (measured at binding potential) of available striatal D2/D3 receptors has been shown to predict trait impulsiveness. This relationship is highly robust and well replicated. In each case, however, the availability of dopamine receptors was measured at rest. More broadly, the extent to which relationships between dopamine receptor availability and behavioral traits hold when participants perform a cognitive task is unclear. Furthermore, the performance of a cognitive task engages fundamentally different neural networks than are maximally engaged during the resting state. This complicates interpretation of previously observed correlations, which could be influenced by two distinct factors. The first is variation in available receptor density, which reflects a stable trait of the individual. The second is variation in context-specific dopamine release, which differentially displaces some dopamine radiotracers (such as raclopride) across individuals. Using an existing data set, we related trait impulsiveness, as measured using the Barratt Impulsiveness Scale (BIS-11), to the density (binding potential) of available striatal D2/D3 receptors as measured using positron emission tomography (PET) with [11C]raclopride. Importantly, the PET scan was completed while participants performed an attention-demanding visual search task. We replicate robust correlations between this measure of receptor availability and trait impulsiveness previously demonstrated during the resting state, extending this relationship to periods of active task engagement. Our results support the idea that this relationship depends on striatal D2/D3 receptor density and not on context-dependent dopamine release. NEW & NOTEWORTHY Several studies have demonstrated a relationship between the density of available striatal D2/D3 receptors and trait impulsiveness. However, in each case, the availability of dopamine receptors was measured during the resting state. This complicates interpretation of previously observed correlations, which could be influenced by either stable variation in receptor density or context-dependent dopamine release. We present evidence uniquely consistent with the former interpretation, providing clarity to the nature of this brain-behavior relationship.

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Effect of Subthalamic Nucleus Stimulation during Exercise on the Mesolimbocortical Dopaminergic Region in Parkinson'S Disease: A Positron Emission Tomography Study

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2012.183 ◽

2012 ◽

Vol 33 (3) ◽

pp. 415-421 ◽

Cited By ~ 10

Author(s):

Takao Nozaki ◽

Kenji Sugiyama ◽

Shunsuke Yagi ◽

Etsuji Yoshikawa ◽

Toshihiko Kanno ◽

...

Keyword(s):

Positron Emission Tomography ◽

Subthalamic Nucleus ◽

Dopamine Release ◽

Motor Behavior ◽

Dopamine Neurons ◽

Emission Tomography ◽

Binding Potential ◽

Positron Emission ◽

Motor Loop ◽

Stn Dbs

To elucidate the dynamic effects of deep brain stimulation (DBS) in the subthalamic nucleus (STN) during activity on the dopaminergic system, 12 PD patients who had STN-DBS operations at least 1 month prior, underwent two positron emission tomography scans during right-foot movement in DBS-off and DBS-on conditions. To quantify motor performance changes, the motion speed and mobility angle of the foot at the ankle were measured twice. Estimations of the binding potential of [11C]raclopride (BPND) were based on the Logan plot method. Significant motor recovery was found in the DBS-on condition. The STN-DBS during exercise significantly reduced the [11C]raclopride BPND in the caudate and the nucleus accumbens (NA), but not in the dorsal or ventral putamen. The magnitude of dopamine release in the NA correlated negatively with the magnitude of motor load, indicating that STN-DBS facilitated motor behavior more smoothly and at less expense to dopamine neurons in the region. The lack of dopamine release in the putamen and the significant dopamine release in the ventromedial striatum by STN-DBS during exercise indicated dopaminergic activation occurring in the motivational circuit during action, suggesting a compensatory functional activation of the motor loop from the nonmotor to the motor loop system.

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Hierarchical Modelling of Facial Perceptions: A Secondary Analysis of Aggressiveness Ratings

10.31234/osf.io/5bv2p ◽

2020 ◽

Author(s):

Mark Christopher Adkins ◽

Nataly Beribisky ◽

Stephan Bonfield ◽

Linda Farmus

Keyword(s):

Factor Analysis ◽

Mixed Model ◽

Structural Information ◽

Secondary Analysis ◽

Specific Factor ◽

Primary Analysis ◽

Model Framework ◽

Psychological Science ◽

Individual Traits ◽

Confirmatory Factor

The Psychological Science Accelerator’s (PSA) primary project tested for latent structure using exploratory factor analysis and confirmatory factor analysis but we decided to diverge from this approach and model individual traits separately. Our interest mainly was in examining the interplay between “stimulus ethnicity” and “stimulus sex” to discover how differing levels of these criterion differ across region, country, lab etc. While the necessary and prerequisite hierarchical structural information about each trait could certainly be found within the primary project’s dataset, we did not assume that any specific factor structure from the PSA’s primary analysis would necessarily hold, therefore we based our decision to model the data from each trait separately using a mixed model framework.

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