scholarly journals Predicting effects of methylphenidate and sulpiride on brain and cognition: A pharmaco-fMRI, PET study. Design and descriptives.

2021 ◽  
Author(s):  
Jessica I Määttä ◽  
Ruben van den Bosch ◽  
Danae Papadopetraki ◽  
Lieke Hofmans ◽  
Britt Lambregts ◽  
...  
Keyword(s):  
Working Memory ◽  
Working Memory Capacity ◽  
Drug Effects ◽  
Striatal Dopamine ◽  
Dopamine Synthesis ◽  
Healthy Population ◽  
Blink Rate ◽  
Dopaminergic Drugs ◽  
Positron Emission ◽  
Cognitive Paradigms

The large variation observed in the effects of dopaminergic drugs poses a major problem for neuropsychiatry, where therapeutic drugs may be ineffective or detrimental in a proportion of patients, but also for the healthy population. We have conducted a pharmaco-fMRI/PET study in 100 healthy participants to investigate the neural and neurochemical mechanisms of this variability. We studied the cognitive effects of methylphenidate (20mg) and sulpiride (400mg) across various cognitive domains, such as reward learning and motivation, working memory and effort motivation. To establish the baseline dopamine-dependency of the drug effects, all participants underwent an [18F]DOPA positron emission tomography scan on a separate off-drug session to quantify their baseline striatal dopamine synthesis capacity. In addition, multiple putative proxy measures of striatal dopamine activity were acquired, including spontaneous eye blink rate, trait impulsivity, subjective reward sensitivity and working memory capacity. The drug effects on each of the cognitive paradigms and their potential dependency on dopamine synthesis capacity and putative proxy measures are reported in separate papers. In the present paper, we report the design of the full study, as well as drug effects on subjective mood and autonomic arousal. This report aims to serve as a reference for future pharmacological fMRI/PET studies as well as for the specific papers resulting from detailed analyses of the included cognitive paradigms. The study will enable the development of a proxy-model of baseline dopamine, intended to provide a pragmatic handle on predicting the effects of dopaminergic drugs on brain and cognition that maximally generalizes to new participants.

scholarly journals Correlations of striatal dopamine synthesis with default network deactivations during working memory in younger adults

2010 ◽  
Vol 32 (6) ◽  
pp. 947-961 ◽  
Author(s):  
Meredith N. Braskie ◽  
Susan M. Landau ◽  
Claire E. Wilcox ◽  
Stephanie D. Taylor ◽  
James P. O'Neil ◽  
...  
Keyword(s):  
Working Memory ◽  
Striatal Dopamine ◽  
Dopamine Synthesis ◽  
Default Network ◽  
Younger Adults

scholarly journals Tracking Real-Time Changes in Working Memory Updating and Gating with the Event-Based Eye-Blink Rate

2017 ◽  
Author(s):  
Rachel Rac-Lubashevsky ◽  
Heleen A. Slagter ◽  
Yoav Kessler
Keyword(s):  
Working Memory ◽  
Cognitive Processes ◽  
Striatal Dopamine ◽  
Blink Rate ◽  
Eye Blink ◽  
Non Invasive ◽  
Working Memory Updating ◽  
Time Changes ◽  
Event Based ◽  
Gating Process

AbstractEffective working memory (WM) functioning depends on the gating process that regulates the balance between maintenance and updating of WM. The present study used the event-based eye-blink rate (ebEBR), which presumably reflects phasic striatal dopamine activity, to examine how the cognitive processes of gating and updating separately facilitate flexible updating of WM contents and the potential involvement of dopamine in these processes. Realtime changes in eye blinks were tracked during performance on the reference-back task, in which demands on these two processes were independently manipulated. In all three experiments, trials that required WM updating and trials that required gate switching were both associated with increased ebEBR. These results may support the prefrontal cortex basal ganglia WM model (PBWM) by linking updating and gating to striatal dopaminergic activity. In Experiment 3, the ebEBR was used to determine what triggers gate switching. We found that switching to an updating mode (gate opening) was more stimulus driven and retroactive than switching to a maintenance mode, which was more context driven. Together, these findings show that the ebEBR – an inexpensive, non-invasive, easy-to-use measure – can be used to track changes in WM demands during task performance and, hence, possibly striatal dopamine activity.

scholarly journals Effective Connectivity and Dopaminergic Function of Fronto-Striato-Thalamic Circuitry in First-Episode Psychosis, Established Schizophrenia, and Healthy Controls

2021 ◽  
Author(s):  
Kristina Sabaroedin ◽  
Adeel Razi ◽  
Sidhant Chopra ◽  
Nancy Tran ◽  
Andrii Pozaruk ◽  
...  
Keyword(s):  
Symptom Severity ◽  
Effective Connectivity ◽  
First Episode Psychosis ◽  
Striatal Dopamine ◽  
Positive Symptom ◽  
Dopamine Synthesis ◽  
First Episode ◽  
Positron Emission ◽  
Episode Psychosis ◽  
Patient Groups

Dysfunction of fronto-striato-thalamic (FST) circuits is thought to contribute to dopaminergic dysfunction and symptom onset in psychosis, but it remains unclear whether this dysfunction is driven by aberrant bottom-up subcortical signaling or impaired top-down cortical regulation. Here, we used spectral dynamic causal modelling (DCM) of resting-state functional magnetic resonance imaging (fMRI) to characterize the effective connectivity of dorsal and ventral FST circuits in a sample of 46 antipsychotic-naive first-episode psychosis (FEP) patients and 23 controls and an independent sample of 36 patients with established schizophrenia (SCZ) patients and 100 controls. We found that midbrain and thalamic connectivity were implicated across both patient groups. Dysconnectivity in FEP patients was mainly restricted to the subcortex, with positive symptom severity being associated with midbrain connectivity. Dysconnectivity between the cortex and subcortical systems was only apparent in SCZ patients. In another independent sample of 33 healthy individuals who underwent concurrent fMRI and [18F]DOPA positron emission tomography, we found that striatal dopamine synthesis capacity was associated with the effective connectivity of nigrostriatal and striatothalamic pathways, implicating similar circuits as those associated with psychotic symptom severity in patients. Our findings thus indicate that subcortical dysconnectivity is salient in the early stages of psychosis, that cortical dysfunction may emerge later in the illness, and that nigrostriatal and striatothalamic signaling are closely related to striatal dopamine synthesis capacity, which is a robust risk marker for psychosis.

Striatal dopamine synthesis capacity in twins discordant for schizophrenia

2011 ◽  
Vol 41 (11) ◽  
pp. 2331-2338 ◽  
Author(s):  
P. Shotbolt ◽  
P. R. Stokes ◽  
S. F. Owens ◽  
T. Toulopoulou ◽  
M. M. Picchioni ◽  
...  
Keyword(s):  
Control Sample ◽  
Chronic Schizophrenia ◽  
Striatal Dopamine ◽  
Psychotic Symptoms ◽  
Dopamine Synthesis ◽  
Control Group ◽  
Positron Emission ◽  
Syndrome Scale ◽  
Increased Risk

BackgroundElevated striatal dopamine synthesis capacity is thought to be fundamental to the pathophysiology of schizophrenia and has also been reported in people at risk of psychosis. It is therefore unclear if striatal hyperdopaminergia is a vulnerability marker for schizophrenia, or a state feature related to the psychosis itself. Relatives of patients with schizophrenia are themselves at increased risk of developing the condition. In this study we examined striatal dopamine synthesis capacity in both members of twin pairs discordant for schizophrenia.MethodIn vivo striatal dopamine synthesis capacity was examined using fluorine-18-l-dihydroxyphenylalanine (18F-DOPA) positron emission tomography (PET) scans in seven twin pairs discordant for schizophrenia and in a control sample of 10 healthy control twin pairs.ResultsStriatal 18F-DOPA uptake was not elevated in the unaffected co-twins of patients with schizophrenia (p=0.65) or indeed in the twins with schizophrenia (p=0.89) compared to the control group. Levels of psychotic symptoms were low in the patients with schizophrenia who were in general stable [mean (s.d.) Positive and Negative Syndrome Scale (PANSS) total=56.8 (25.5)] whereas the unaffected co-twins were largely asymptomatic.ConclusionsStriatal dopamine synthesis capacity is not elevated in symptom-free individuals at genetic risk of schizophrenia, or in well-treated stable patients with chronic schizophrenia. These findings suggest that striatal hyperdopaminergia is not a vulnerability marker for schizophrenia.

scholarly journals Working Memory Capacity Predicts Dopamine Synthesis Capacity in the Human Striatum

2008 ◽  
Vol 28 (5) ◽  
pp. 1208-1212 ◽  
Author(s):  
R. Cools ◽  
S. E. Gibbs ◽  
A. Miyakawa ◽  
W. Jagust ◽  
M. D'Esposito
Keyword(s):  
Working Memory ◽  
Working Memory Capacity ◽  
Memory Capacity ◽  
Dopamine Synthesis

scholarly journals Overeating Behavior and Striatal Dopamine with 6--Fluoro-L--Tyrosine PET

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Claire E. Wilcox ◽  
Meredith N. Braskie ◽  
Jennifer T. Kluth ◽  
William J. Jagust
Keyword(s):  
Positron Emission Tomography ◽  
Weight Loss ◽  
Eating Behavior ◽  
Healthy Subjects ◽  
Striatal Dopamine ◽  
Emission Tomography ◽  
Dopamine Synthesis ◽  
Positron Emission ◽  
Age And Sex

Eating behavior may be affected by dopamine synthesis capacity. In this study, 6--fluoro-L--tyrosine (FMT) positron emission tomography (PET) uptake in striatal subregions was correlated with BMI (kg/) and an estimate of the frequency of prior weight loss attempts in 15 healthy subjects. BMI was negatively correlated with FMT uptake in the dorsal caudate. Although the association between BMI and FMT uptake in the dorsal caudate was not significant upon correction for age and sex, the association fell within the range of a statistical trend. Weight loss attempts divided by years trying was also negatively correlated with FMT uptake in the dorsal putamen . These results suggest an association between low dorsal striatal presynaptic dopamine synthesis capacity and overeating behavior.

scholarly journals Cerebral [18F]-FDOPA Uptake in Autism Spectrum Disorder and Its Association with Autistic Traits

Diagnostics ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2404
Author(s):  
Rik Schalbroeck ◽  
Lioe-Fee de Geus-Oei ◽  
Jean-Paul Selten ◽  
Maqsood Yaqub ◽  
Anouk Schrantee ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Region Of Interest ◽  
Autistic Traits ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Striatal Dopamine ◽  
Dopamine Synthesis ◽  
Autism Spectrum Quotient ◽  
Positron Emission ◽  
Autistic Adults

Dopaminergic signaling is believed to be related to autistic traits. We conducted an exploratory 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine positron emission tomography/computed tomography ([18F]-FDOPA PET/CT) study, to examine cerebral [18F]-FDOPA influx constant (kicer min−1), reflecting predominantly striatal dopamine synthesis capacity and a mixed monoaminergic innervation in extrastriatal neurons, in 44 adults diagnosed with autism spectrum disorder (ASD) and 22 controls, aged 18 to 30 years. Autistic traits were assessed with the Autism Spectrum Quotient (AQ). Region-of-interest and voxel-based analyses showed no statistically significant differences in kicer between autistic adults and controls. In autistic adults, striatal kicer was significantly, negatively associated with AQ attention to detail subscale scores, although Bayesian analyses did not support this finding. In conclusion, among autistic adults, specific autistic traits can be associated with reduced striatal dopamine synthesis capacity. However, replication of this finding is necessary.

scholarly journals Striatal dopamine dissociates methylphenidate effects on value-based versus surprise-based reversal learning

2021 ◽  
Author(s):  
Ruben van den Bosch ◽  
Britt Lambregts ◽  
Jessica Määttä ◽  
Lieke Hofmans ◽  
Danae Papadopetraki ◽  
...  
Keyword(s):  
Reversal Learning ◽  
Learning Task ◽  
Striatal Dopamine ◽  
Emission Tomography ◽  
Sensory Cortex ◽  
Dopamine Synthesis ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Large Variability ◽  
Positron Emission

Abstract Psychostimulants such as methylphenidate are widely used for their cognitive enhancing effects, but there is large variability in the direction and extent of these effects, and there are concerns about the potential for abuse. We tested the hypothesis that methylphenidate enhances or impairs reward/punishment-based reversal learning depending on baseline striatal dopamine levels and corticostriatal gating of reward/punishment-related representations in stimulus-specific sensory cortex. Young healthy adults were scanned with functional magnetic resonance imaging during a reward/punishment reversal learning task, after intake of methylphenidate or the selective D2/3-receptor antagonist sulpiride. Striatal dopamine synthesis capacity was indexed with [18F]DOPA positron emission tomography. Reward versus punishment learning signals were boosted to a greater degree in participants with higher dopamine synthesis capacity. By contrast, striatal and stimulus-specific sensory surprise signals were boosted in participants with lower dopamine synthesis. These results unravel the mechanisms by which methylphenidate modulates reward and attention, impacting our understanding of how it can both enhance attention and mitigate reward-related compulsivity.

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