We used positron emission tomography imaging with [C]raclopride to examine the effects of consumption of alcohol or placebo beverage by participants with alcohol use disorder (AUD) compared with healthy participants with and without... more
We used positron emission tomography imaging with [C]raclopride to examine the effects of consumption of alcohol or placebo beverage by participants with alcohol use disorder (AUD) compared with healthy participants with and without family history of AUD. We sought to assess dopamine release following alcohol exposure in relation to AUD risk. Three groups were enrolled: participants with AUD (n = 15) and healthy participants with family history negative (n = 34) or positive (n = 16) for AUD. Participants consumed a placebo (n = 65) or alcohol (n = 63) beverage in counterbalanced order before positron emission tomography scanning (128 scans). Binding potential (BP) in the two drink conditions and the percent change in BP between conditions were evaluated across striatal subregions. Subjective effects of beverage consumption were rated. Effects of group, drink order, and sex were evaluated. Alcohol resulted in greater dopamine release than did placebo in the ventral striatum (p < ....
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Research Interests: Neuroscience, Psychology, Psychosis, Schizophrenia, Medicine, and 15 moreDopamine, Brain Mapping, Humans, Cerebral Cortex, Female, Male, Synaptic Transmission, Middle Aged, Adult, Case Control Studies, Statistics as Topic, Psychiatric Status Rating Scales, dopaminergic, Corpus striatum, and Positron emission tomography computed tomography
All currently available antipsychotic medications bind to both the dopamine-2 (D2) and dopamine-3 (D3) receptors in vitro. However, there is conflicting evidence from in vivo studies about whether or not antipsychotic medications bind to... more
All currently available antipsychotic medications bind to both the dopamine-2 (D2) and dopamine-3 (D3) receptors in vitro. However, there is conflicting evidence from in vivo studies about whether or not antipsychotic medications bind to the D3 receptor (D3R). The purpose of this study was to determine whether acute doses of risperidone bind to the D3R in humans. We performed PET scans on an mCT scanner with [(11)C]-(+)-PHNO injected as a bolus, before and after a 2mg oral dose of risperidone in five medication free subjects with schizophrenia. The subjects were scanned for 120min and underwent an MRI scan for region of interest delineation and coregistration. Cerebellum was used as a reference region. Simplified reference tissue modeling (SRTM) was used to calculate BPND. We observed binding to the D3R receptor by risperidone as evidenced by observable occupancy in regions in which the [(11)C]-(+)-PHNO signal is almost exclusively from the D3R (i.e., substantia nigra/ventral tegmen...
Research Interests: Pharmacology, Psychology, Schizophrenia, Magnetic Resonance Imaging, Positron Emission Tomography, and 15 moreMedicine, Brain Mapping, Brain, Humans, Female, Male, Middle Aged, Adult, RISPERIDONE, Antipsychotic, Protein Binding, Psychiatric Status Rating Scales, Psychology and Cognitive Sciences, Medical and Health Sciences, and Oxazines
Purpose: Pharmacological evidence suggests abnormalities in the brain serotonin (5-HT) system in obsessive–compulsive disorder (OCD) involving cortical 5-HT2A receptors. However, recent animal and human studies have also implicated the... more
Purpose: Pharmacological evidence suggests abnormalities in the brain serotonin (5-HT) system in obsessive–compulsive disorder (OCD) involving cortical 5-HT2A receptors. However, recent animal and human studies have also implicated the glutamate system in OCD. Animal studies found that disrupting glutamatergic signaling at cortico-striatal synapses leads to OCD-like behaviors, human genetic studies demonstrated associations between the glutamate transporter SLC1A1 and OCD, and case studies and open label trials demonstrated efficacy of glutamatergic agents in reducing OCD symptoms. This has led to the hypothesis that OCD symptoms result either directly or indirectly from increased glutamatergic signaling in cortico-striatal pathways. As 5-HT2A receptors are located on both pyramidal cells and interneurons and may modulate glutamate and GABA transmission, we measured 5-HT2A receptor availability with PET, and Glx (glutamate plus glutamine) and GABA levels with MRS in OCD patients and matched controls.
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Research Interests: Psychology, Positron Emission Tomography, Medicine, Brain, Humans, and 14 moreAggression, Female, Serotonin Transporter, Male, Sulfides, Middle Aged, Adult, Analysis of Variance, Obssessive Compulsive Personality Disorder, Psychiatric, aniline Compounds, Statistics as Topic, Psychology and Cognitive Sciences, and Medical and Health Sciences
Introduction: Low striatal dopamine 2 receptor (D2) availability and low ventrostriatal (VST) dopamine (DA) release have been observed in alcoholism, cocaine and heroin dependence. Less is known about the DAergic system in cannabis... more
Introduction: Low striatal dopamine 2 receptor (D2) availability and low ventrostriatal (VST) dopamine (DA) release have been observed in alcoholism, cocaine and heroin dependence. Less is known about the DAergic system in cannabis dependence. We assessed D2 availability and DA release in cannabis dependence and explored the effects of early age of onset (AOO) on these parameters, using [11C]raclopride PET and the amphetamine challenge paradigm.
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D1 receptors are the main mediators of dopamine transmission in the cortex and subserve cognitive functions that are affected in patients with schizophrenia. Prior imaging studies have suggested abnormalities in the expression of these... more
D1 receptors are the main mediators of dopamine transmission in the cortex and subserve cognitive functions that are affected in patients with schizophrenia. Prior imaging studies have suggested abnormalities in the expression of these receptors in schizophrenia, but no conclusive picture has emerged yet. One source of discrepancy may have been prior antipsychotic exposure. The goal of this study was to determine D1 receptor expression in separate groups of patients with schizophrenia, with or without prior antipsychotic exposure, compared to respectively matched controls.
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Research Interests: Cognitive Science, Magnetic Resonance Imaging, Adolescent, Medicine, Brain Mapping, and 15 moreHumans, Major Depressive Disorder, Female, Male, Autism Spectrum Disorder, Clinical Sciences, Middle Aged, Adult, Asperger Syndrome, Healthy Subjects, Neurosciences, Piperidines, Outcome measure, Compartment Model, and Medical and Health Sciences
Research Interests: Depression, Neuropsychopharmacology, Positron Emission Tomography, Medicine, Dopamine, and 15 moreBrain, Humans, Internal Medicine, Cerebral Cortex, Female, Male, Pituitary Gland, Adult, Brain Chemistry, Aripiprazole, Benzamides, Partial Agonist, Corpus striatum, Antipsychotic agents, and Medical and Health Sciences
Research Interests: Computer Science, Chemistry, Nuclear medicine, Neuropsychopharmacology, Medicine, and 15 moreNeuroimmunology, Dopamine, Papio, Brain, PET imaging, Animals, Neuroimage, Male, In Vivo, Globus Pallidus, Functional Testing, Antipsychotic agents, ORIGINAL ARTICLE, Medical and Health Sciences, and Oxazines
Purpose: 3-(6-methyl-pyridin-2-ylethynyl)-cyclohex-2-enone-O-C-methyl-oxime ([C]-ABP688) is a highly-selective antagonist PET tracer for imaging the metabotropic glutamate receptor subtype 5 (mGluR5). The aims of this study were to test... more
Purpose: 3-(6-methyl-pyridin-2-ylethynyl)-cyclohex-2-enone-O-C-methyl-oxime ([C]-ABP688) is a highly-selective antagonist PET tracer for imaging the metabotropic glutamate receptor subtype 5 (mGluR5). The aims of this study were to test the reproducibility of outcome measures using this tracer with anesthetized baboons and to test the effect of challenge with the glutamate releaser N-acetylcysteine (NAC) on [C]-ABP688 specific binding.
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Introduction:Dopamine (DA)plays a role in thepathophysiologyof both schizophrenia and addiction. Imaging studies have shown thatDA is increased in the associative striatum(AST), and specifically in the precommissural caudate, in... more
Introduction:Dopamine (DA)plays a role in thepathophysiologyof both schizophrenia and addiction. Imaging studies have shown thatDA is increased in the associative striatum(AST), and specifically in the precommissural caudate, in schizophrenia,while it is blunted in addiction, predominantly in the ventral striatum(VST).Wehypothesized that subjects suffering fromboth schizophrenia and addictionmayhave both alterations. Here,we assessedD2 receptors and DA transmission in striatal subregions with [C]raclopride PET and the amphetamine challenge paradigm.
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The dopamine D1 receptor antagonist radioligand [11C]NNC 112 has previously been reported to have 100-fold selectivity for the D1 receptor compared with the serotonin 5-HT2A receptor. In this study, we tested the selectivity by scanning... more
The dopamine D1 receptor antagonist radioligand [11C]NNC 112 has previously been reported to have 100-fold selectivity for the D1 receptor compared with the serotonin 5-HT2A receptor. In this study, we tested the selectivity by scanning seven healthy human research volunteers with [11C]NNC 112 before and after 2mg of the antipsychotic drug risperidone, a dose that putatively blocks all 5-HT2A receptors with negligible effect on D1 receptors. We found that specific binding in cortical regions was reduced by 20% to 30%, whereas the striatum showed no change. Based on the known relative densities of these receptors in humans, our results suggest 5- to 10-fold selectivity of [11C]NNC 112 for D1 versus 5-HT2A as opposed to 100-fold selectivity. These results suggest caution in interpreting data from studies using this tracer to measure cortical D1 receptors as well as the need for more selective radioligands to assess cortical D1 receptors.
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D(1) receptors are the main mediators of dopamine transmission in the cortex and subserve cognitive functions that are affected in patients with schizophrenia. Prior imaging studies have suggested abnormalities in the expression of these... more
D(1) receptors are the main mediators of dopamine transmission in the cortex and subserve cognitive functions that are affected in patients with schizophrenia. Prior imaging studies have suggested abnormalities in the expression of these receptors in schizophrenia, but no conclusive picture has emerged yet. One source of discrepancy may have been prior antipsychotic exposure. We used positron emission tomography (PET) and a D1 radiotracer, [(11)C]NNC112, in drug naïve (DN, n = 12) and drug free (DF, n = 13) patients with schizophrenia and 40 healthy control subjects (HC, n = 40 total, n = 24 per comparison group) matched for age, gender, ethnicity, parental socioeconomic status and cigarette smoking. We measured the binding potential BPP, corrected for partial volume effects. The outcome measure was obtained in cortical and striatal subregions outlined on coregistered individual MRIs. Partial volume effect corrected BPP measures were significantly higher in DN vs controls in cortica...
Research Interests: Psychology, Psychopharmacology, Magnetic Resonance Imaging, Positron Emission Tomography, Medicine, and 15 morePrefrontal Cortex, Dopamine, Humans, Internal Medicine, Female, Male, Adult, Cognitive Function, Antipsychotic, Dorsolateral Prefrontal Cortex, Outcome measure, Antipsychotic agents, Psychology and Cognitive Sciences, Medical and Health Sciences, and Cigarette Smoke
Research Interests: Pharmacology, Chemistry, Biology, Medicine, Biological Sciences, and 15 moreBiological Psychiatry, Brain Mapping, Papio, Glutamate, Brain, Animals, Metabotropic Glutamate Receptors, Male, In Vivo, Oximes, Glutamic Acid, Glutamate Receptor, Psychology and Cognitive Sciences, Medical and Health Sciences, and acetylcysteine
Research Interests: Positron Emission Tomography, Medicine, Biological Sciences, Biological Psychiatry, Dopamine, and 15 moreBrain Mapping, Humans, Internal Medicine, Age, Female, Male, Adult, Analysis of Variance, Neocortex, Age Factors, Protein Binding, Case Control Studies, Corpus striatum, Antipsychotic agents, and Medical and Health Sciences
Research Interests: Magnetic Resonance Imaging, Adolescent, Positron Emission Tomography, Medicine, Biological Sciences, and 15 moreBiological Psychiatry, Humans, Female, Male, Biological, Obsessive Compulsive Disorder, Orbitofrontal cortex, Middle Aged, Entorhinal Cortex, Adult, Limbic System, Isotope Labeling, Age of Onset, Piperidines, and Medical and Health Sciences
Research Interests: Psychology, Personality Disorders, Positron Emission Tomography, Medicine, Biological Sciences, and 15 moreBiological Psychiatry, Humans, Aggression, Female, Personality Disorder, Male, Biological, Orbitofrontal cortex, Middle Aged, Adult, Frontal Lobe, Piperidines, Impulsive behavior, Psychology and Cognitive Sciences, and Medical and Health Sciences
Research Interests: Addiction, Magnetic Resonance Imaging, Medicine, Biological Sciences, Biological Psychiatry, and 15 moreDopamine, Brain Mapping, Humans, Internal Medicine, Caudate Nucleus, Female, Alcohol Drinking, Male, Biological, Amphetamine, Alcohol dependence, Adult, Basal ganglia, Corpus striatum, and Medical and Health Sciences
A fast fluid method using inverse filtering for medical image registration task is presented in this paper. We extend the one dimensional LMS inverse filtering method to two dimensions and successfully implement it in the fluid... more
A fast fluid method using inverse filtering for medical image registration task is presented in this paper. We extend the one dimensional LMS inverse filtering method to two dimensions and successfully implement it in the fluid registration method first introduced by Christensen. The experiment results show the performance of fluid algorithm is sped up by a factor of about 2.5