Fluorodopa Uptake Research Articles

Slowing of EEG waves correlates with striatal [18 F]fluorodopa PET/CT uptake and executive dysfunction in Parkinson's disease.

Parkinson's disease (PD) research on specific neuroimaging and neurophysiological biomarkers revealing executive dysfunction mechanisms is limited, necessitating validation. Thus, our study aimed to assess associations between electroencephalographic power spectral density (PSD-EEG), striatal [18 F]Fluorodopa uptake and neuropsychological executive function (EF) testing parameters in PD, while also estimating their diagnostic accuracy. We compared resting PSD-EEG, striatal [18 F]Fluorodopa uptake ratios based on positron emission computed tomography ([18 F]FDOPA PET/CT) and neuropsychological EF tests outcomes [Trail Making Test (TMT) and Stroop Test (ST)] between PD patients and healthy controls (HCO) and then calculated correlations among these measures separately for each group. Additionally, we estimated PD diagnostic accuracy of the PSD-EEG and [18 F]FDOPA PET/CT parameters. In PD patients, we observed the following: (i) slower EEG waves, reflected in increased power of the EEG theta and lower-alpha bands in frontal lobe areas; (ii) reduced [18 F]FDOPA PET/CT uptake in the putaminal and caudate nuclei, along with a decreased putamen-to-caudate ratio ([18 F]FDOPA PET/CT PCR); and (iii) longer performance times evident in nearly all EF tests' parameters. Slower EEG waves correlated negatively with [18 F]FDOPA PET/CT PCR and positively with most of the EF test parameters. Furthermore, we found negative correlations between [18 F]FDOPA PET/CT PCR and certain EF measures related to ST. [18 F]FDOPA PET/CT ratios and several PSD-EEG parameters, particularly those from the prefrontal cortex, demonstrated clinically reasonable diagnostic accuracy for PD. In conclusion, EEG waves slowing in the frontal lobe were correlated with striatal dopaminergic deficiency and impaired executive function in mild PD patients and showed promise as a biomarker of PD-related executive dysfunction.

Longitudinal Positron Emission Tomography of Dopamine Synthesis in Subjects with GBA1 Mutations.

Mutations in GBA1, the gene mutated in Gaucher disease, are a common genetic risk factor for Parkinson disease, although the penetrance is low. We performed [18 F]-fluorodopa positron emission tomography studies of 57 homozygous and heterozygous GBA1 mutation carriers (15 with parkinsonism) and 98 controls looking for early indications of dopamine loss using voxelwise analyses to identify group differences in striatal [18 F]-fluorodopa uptake (Ki ). Forty-eight subjects were followed longitudinally. Cross-sectional and longitudinal comparisons of Ki and Ki change found significant effects of Parkinson disease. However, at baseline and over time, striatal [18 F]-fluorodopa uptake in mutation carriers without parkinsonism did not significantly differ from controls. ANN NEUROL 2020;87:652-657.

Hereditary dystonia and parkinsonism: two sides of the same coin?

This scientific commentary refers to ‘Parkinson’s disease in GTP cyclohydrolase 1 mutation carriers’, by Mencacci et al. (doi:10/1093/brain/awu179). A number of inherited disorders are marked by combined dystonia and parkinsonism, and the genetic basis of many of these has now been identified. They include putative ‘neurofunctional’ conditions with dystonia-parkinsonism, such as DOPA-responsive dystonia caused by mutations in the GTP cyclohydrolase 1 ( GCH1 ) gene, as well as neurodegenerative diseases that present with predominant parkinsonism, frequently accompanied by dystonic features, i.e. ‘parkinsonism-dystonia’, as seen in carriers of parkin ( PARK2 ) and PINK1 mutations. Because dystonia can be the presenting sign in parkinsonism-dystonias (Grunewald et al. , 2013) and, conversely, patients with DOPA-responsive dystonia can present with isolated parkinsonism (Grimes et al. , 2002; Tadic et al. , 2012), it can be difficult to categorize individual patients solely on clinical grounds. The boundaries between dystonia and parkinsonism may thus be less well defined than previously thought, and this calls for detailed longitudinal phenotyping of patients. Indeed, despite the advent of next-generation sequencing and increased availability of diagnostic testing—resulting in a wealth of genetic data—systematic genotype–phenotype evaluations lag behind advances in genetics and have largely yet to be translated into clinical practice (Grunewald et al. , 2013). In this issue of Brain , Mencacci et al. elegantly address the phenomenon of prominent parkinsonism in carriers of GCH1 mutations (Mencacci et al. , 2014). Prompted by their observation that relatives of patients with DOPA-responsive dystonia can present with pure ‘Parkinson’s disease’, they systematically collected and examined four such unrelated pedigrees harbouring GCH1 mutations and reviewed the literature for similar reports. This resulted in a total of eight cases from different ethnic backgrounds with predominant parkinsonism, all of whom had a mostly asymmetrical reduction in dopamine transporter density or fluorodopa uptake, in …

Validation of midbrain positron emission tomography measures for nigrostriatal neurons in macaques

Development of an effective therapy to slow the inexorable progression of Parkinson disease requires a reliable, objective measurement of disease severity. In the present study, we compare presynaptic positron emission tomography (PET) tracer uptake in the substantia nigra (SN) to cell loss and motor impairment in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated nonhuman primates. Presynaptic PET tracers 6-[(18)F]-fluorodopa (FD), [(11)C]-2β-methoxy-3β-4-fluorophenyltropane (CFT), and [(11)C]-dihydrotetrabenazine (DTBZ) were used to measure specific uptake in the SN and striatum before and after a variable dose of MPTP in nonhuman primates. These in vivo PET-based measures were compared with motor impairment, as well as postmortem tyrosine hydroxylase-positive cell counts and striatal dopamine concentration. We found the specific uptake of both CFT and DTBZ in the SN had a strong, significant correlation with dopaminergic cell counts in the SN (R(2) = 0.77, 0.53, respectively, p < 0.001), but uptake of FD did not. Additionally, both CFT and DTBZ specific uptake in the SN had a linear relationship with motor impairment (rs = -0.77, -0.71, respectively, p < 0.001), but FD uptake did not. Our findings demonstrate that PET-measured binding potentials for CFT and DTBZ for a midbrain volume of interest targeted at the SN provide faithful correlates of nigral neuronal counts across a full range of lesion severity. Because these measures correlate with both nigral cell counts and parkinsonian ratings, we suggest that these SN PET measures are relevant biomarkers of nigrostriatal function.

Validation of nigrostriatal positron emission tomography measures: Critical limits

Molecular imaging and clinical endpoints are frequently discordant in Parkinson disease clinical trials, raising questions about validity of these imaging measures to reflect disease severity. We compared striatal uptake for 3 positron emission tomography (PET) tracers with in vitro measures of nigral cell counts and striatal dopamine in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. Sixteen macaques had magnetic resonance imaging and baseline PETs using 6-[18F]fluorodopa (FD), [11C]dihydrotetrabenazine (DTBZ), and 2beta-[11 C]carbomethoxy-3beta-(4-fluorophenyl)tropane (CFT). MPTP (0-0.31 mg/kg) infused unilaterally via the internal carotid artery produced stable hemiparkinsonism by 3 weeks. After 8 weeks, PETs were repeated and animals were euthanized for striatal dopamine measurements and unbiased counts of tyrosine hydroxylase-stained nigral cells. Striatal uptake for each radiotracer (FD, DTBZ, CFT) correlated with stereologic nigral cell counts only for nigral loss<50% (r2=0.84, r2=0.86, r2=0.87, p<0.001 respectively; n=10). In contrast, striatal uptake correlated with striatal dopamine over the full range of dopamine depletion (r2=0.95, r2=0.94, r2=0.94, p<0.001; n=16). Interestingly, indices of striatal uptake of FD, DTBZ, and CFT correlated strongly with each other (r2=0.98, p<0.001). Tracer uptake correlated with nigral neurons only when nigral loss was <50%. This along with previous work demonstrating that nigral cell counts correlate strongly with parkinsonism ratings may explain discordant results between neuroimaging and clinical endpoints. Furthermore, strong correlations among striatal uptake for these tracers support lack of differential regulation of decarboxylase activity (FD), vesicular monoamine transporter type 2 (DTBZ), and dopamine transporter (CFT) within 2 months after nigrostriatal injury.

Increased medial orbitofrontal [18F]fluorodopa uptake in Parkinsonian impulse control disorders

Impulse control disorders (ICDs) occur frequently in PD patients. To investigate the possible involvement of the mesostriatal and mesolimbic monoaminergic function in ICDs associated with PD, we examined patients with (n = 10) and without (n = 10) ICDs using the brain [(18) F]fluorodopa PET. Patients with ICDs (e.g., pathological gambling, hypersexuality, and compulsive eating) showed up to 35% higher [(18) F]fluorodopa uptake in the medial orbitofrontal cortex, compared to control patients, but no differences in the striatum. The results remained significant also after excluding subjects with comorbid psychiatric disorders. Increased monoaminergic activity in the medial orbitofrontal cortex might be associated with increased sensitivity for ICDs under dopamine-replacement therapy in PD.

PET studies in Parkinson's disease motor and cognitive dysfunction

Positron emission tomography (PET) has led to significant advances in the knowledge of the neurobiology and pathophysiology of Parkinson's disease (PD) and has also greatly contributed to the understanding of potential mechanisms involved in the development of treatment-induced complications. Initially, PET was mostly used to assess in vivo the severity of the nigrostriatal dopaminergic dysfunction and the resulting motor symptomatology in PD. It has been demonstrated that PET measurements of putaminal dopaminergic function, as measured by [(18)F]-Fluorodopa uptake, correlate well with stages of disease and symptom severity in PD patients, particularly with bradykinesia and rigidity. Analysis of metabolic changes across the brain has identified specific brain networks associated with the main motor features of the disease, including bradykinesia and tremor. In more recent years, the growing availability of new imaging radiotracers for monoaminergic and cholinergic neurons has enabled the evaluation of the non-dopaminergic brain pathways that are likely to be involved in the pathophysiology of non motor symptoms of PD, including depression, fatigue, sleep disorders, and cognitive impairment. Finally, β-amyloid imaging agents have been used to assess the influence of coexistent cortical Alzheimer pathology in PD. This review summarizes the findings from PET studies that have investigated pathophysiology and treatment of motor dysfunction and cognitive impairment in PD.

Using imaging to identify psychogenic parkinsonism before deep brain stimulation surgery

The frequency with which patients with atypical parkinsonism and advanced motor symptoms undergo deep brain stimulation (DBS) procedures is unknown. However, the potential exposure of these patients to unnecessary surgical risks makes their identification critical. As many as 15% of patients enrolled in recent early Parkinson disease (PD) trials have been found to lack evidence of a dopaminergic deficit following PET or SPECT imaging. This suggests that a number of patients with parkinsonism who are referred for DBS may not have idiopathic PD. The authors report on 2 patients with probable psychogenic parkinsonism who presented for DBS surgery. They found that both patients had normal caudate and putamen [(18)F]-fluorodopa uptake on PET imaging, along with normal expression of specific disease-related metabolic networks for PD and multiple system atrophy, a common form of atypical neurodegenerative parkinsonism. The clinical and PET findings in these patients highlight the role of functional imaging in assisting clinical decision making when the diagnosis is uncertain.

A longitudinal study of motor performance and striatal [18F]fluorodopa uptake in Parkinson’s disease

Although [(18)F]fluoro-L: -dopa [FDOPA] positron emission tomography (PET) has been used as a surrogate outcome measure in Parkinson's disease therapeutic trials, this biomarker has not been proven to reflect clinical status longitudinally. We completed a retrospective analysis of relationships between computerized sampling of motor performance, FDOPA PET, and clinical outcome scales, repeated over 4years, in 26 Parkinson's disease (PD) patients and 11 healthy controls. Mixed effects analyses showed that movement time and tongue strength best differentiated PD from control subjects. In the treated PD cohort, motor performance measures changed gradually in contrast to a steady decline in striatal FDOPA uptake. Prolonged reaction and movement time were related to lower caudate nucleus FDOPA uptake, and abnormalities in hand fine force control were related to mean striatal FDOPA uptake. These findings provide evidence that regional loss of nigrostriatal inputs to frontostriatal networks affects specific aspects of motor function.

Rate of 6‐[18F]fluorodopa uptake decline in striatal subregions in Parkinson's disease

Rate of decline in 6-L-[(18)F]fluorodopa (FDOPA) uptake within the striatum has been reported as showing regional differences in Parkinson's disease (PD). We acquired longitudinal brain FDOPA positron emission tomography (PET) studies in 26 PD subjects and 11 controls over 4.5 years. We analyzed both spatially normalized voxel-wise maps of radiotracer influx (Kocc) and average Kocc values for six non-overlapping volumes of interest (VOIs) encompassing the striatum. The voxel-wise analysis showed that in PD, FDOPA Kocc decline spanned the striatum but was greatest in the posterior putamen ipsilateral and anterior putamen contralateral to initial symptoms. The VOI approached showed that absolute rates of Kocc decline were significantly greater in PD than control subjects, but that the slope of decline did not differ between subregions. In PD, ratios of uptake between subregions did not change during the study with the exception of the ipsilateral putamen/caudate ratio. Decline rates were marginally greater during earlier time segments. Both male gender and advancing age were associated with lower baseline FDOPA uptake, but no difference in decline rates. VOI Kocc values were significantly correlated with disease duration, but only moderately correlated with clinical measures. We conclude that FDOPA uptake in subregions of the striatum is strongly correlated with disease duration and age, and declines approximately equally from symptom onset in PD. This implies that in idiopathic PD, relative preservation of uptake in the anterior striatum reflects a delay in pathologic involvement of nigrostriatal projections to this region.

Abnormal Frontostriatal Interactions in People With Prodromal Signs of Psychosis

Alterations in dopaminergic neurotransmission and function of the prefrontal cortex are thought to be central to the pathophysiology of schizophrenia, but the relationship between these factors in the development of psychosis is unclear. To investigate the relationship between striatal dopamine activity and prefrontal function in people at ultra high risk of psychosis. Subjects were studied using functional magnetic resonance imaging while performing a working memory (N-back) task. Positron emission tomography with fluorine 18-labeled fluorodopa was used to investigate presynaptic striatal dopamine activity. Outpatient service for people with prodromal signs of psychosis. Thirty-four subjects participated in the study: 14 healthy volunteers and 20 subjects with an at-risk mental state (ARMS). Regional brain activation (blood oxygen level-dependent response), Ki for [(18)F]fluorodopa uptake, and objective ratings of psychopathology at the time of scanning. In the associative part of the striatum, the Ki for [(18)F]fluorodopa was higher in the ARMS group than in the controls. During the N-back task, ARMS subjects displayed less activation in the right middle frontal gyrus, the medial frontal gyri, and the left superior parietal lobule than controls. The Ki for [(18)F]fluorodopa was positively correlated with activation in the right middle frontal gyrus in controls but negatively correlated with activation in this region in the ARMS group. In people with prodromal signs of psychosis, there are direct correlations between altered prefrontal cortical function and subcortical dopamine synthesis capacity, consistent with the notion that frontostriatal interactions play a critical role in the pathoetiology of schizophrenia.

Response of aged parkinsonian monkeys to in vivo gene transfer of GDNF

This study assessed the potential for functional and anatomical recovery of the diseased aged primate nigrostriatal system, in response to trophic factor gene transfer. Aged rhesus monkeys received a single intracarotid infusion of MPTP, followed one week later by MRI-guided stereotaxic intrastriatal and intranigral injections of lentiviral vectors encoding for glial derived neurotrophic factor (lenti-GDNF) or beta-galactosidase (lenti-LacZ). Functional analysis revealed that the lenti-GDNF, but not lenti-LacZ treated monkeys displayed behavioral improvements that were associated with increased fluorodopa uptake in the striatum ipsilateral to lenti-GDNF treatment. GDNF ELISA of striatal brain samples confirmed increased GDNF expression in lenti-GDNF treated aged animals that correlated with functional improvements and preserved nigrostriatal dopaminergic markers. Our results indicate that the aged primate brain challenged by MPTP administration has the potential to respond to trophic factor delivery and that the degree of neuroprotection depends on GDNF levels.

Progression of dopaminergic dysfunction in a LRRK2 kindred

Little is known about the progression of dopaminergic dysfunction in LRRK2-associated Parkinson disease (PD). We sought to characterize the neurochemical progression with multitracer PET in asymptomatic members of parkinsonian kindred (family D, Western Nebraska) carrying LRRK2 (R1441C) mutation. Thirteen family D subjects underwent PET scans of presynaptic dopaminergic integrity and five subjects were rescanned 2 to 3 years later. In subjects 8, 9 (mutation carriers), and 13 (genealogically at risk subject), there was a decline in PET markers over the course of the study that was significantly greater than the expected rate of decline in healthy controls. Reduced dopamine transporter binding was the earliest indication of subclinical dopaminergic dysfunction and progression to clinical disease was generally associated with the emergence of abnormal fluorodopa uptake. PET study of presymptomatic members of our LRRK2 kindred revealed dopaminergic dysfunction that progressed over time. This represents an ideal group to study the natural history of early disease and the potential effects of neuroprotective interventions.

PET Imaging in Parkinsons Disease

PET imaging first played an important role in the diagnosis of Parkinsons disease (PD) approximately 20 years ago when studies using the newly developed radiotracer, [18F]fluorodopa, demonstrated a clear dopamine loss in the basal ganglia. Other radiotracers were then developed to image presynaptic dopamine transporters, vesicular monoamine transporters and postsynaptic D2 receptor sites. These studies enhanced our understanding of the way in which the dopaminergic system is altered in PD. Shortly after [18F]fluorodeoxyglucose was used to quantify the expression of metabolic brain patterns in PD patients by comparing them with similar studies conducted in healthy volunteers. This dual approach of studying both dopamine and metabolism in the brain has now been applied successfully to diagnose and differentiate typical and atypical parkinsonian syndromes. These imaging biomarkers have since been applied to assess the effects of dopaminergic therapy and surgical techniques like pallidotomy, subthalamic stimulation, embryonic cell implantation, intraputaminal nerve growth factor infusion and viral vector gene therapy. Keywords: Fluorodopa Uptake, Dopamine Transporter, Dopamine Cell Implantation, dopamine receptor density, Glial cell line-derived neurotrophic factor

Striatal Dopamine Synthesis in First-degree Relatives of Patients with Schizophrenia

First degree relatives (FDR) of patients with schizophrenia have higher risk of developing schizophrenia than the general population. Previous positron emission tomography (PET) studies have shown that striatal presynaptic dopamine synthesis capacity is increased in schizophrenia. We investigated whether this same phenomenon is shared by individuals with increased genetic risk for schizophrenia. We used 6-[18F]-fluorodopa (FDOPA) PET imaging to measure striatal dopamine synthesis capacity. We studied 17 nonpsychotic subjects with an FDR with schizophrenia. This group was compared to 17 healthy subjects with no FDRs with schizophrenia. A conventional region of interest (ROI)-analysis indicated that FDOPA uptake (K(i)) in the caudate-putamen was statistically significantly higher in the FDR group than in the control group. A voxel-level analysis confirmed these results. These results suggest that the changes of striatal presynaptic dopamine synthesis seen previously in neuroleptic-naive schizophrenic patients is also present in FDRs of patients with schizophrenia. These findings have implications for the early detection of psychosis as well as for pharmacological interventions in individuals at risk for psychosis.

Joubert syndrome surviving to adulthood associated with a progressive movement disorder

A 48-year-old man presented with a progressive gait disorder. He had longstanding ataxia, oculomotor apraxia, motor delay, and cognitive impairment, diagnosed as cerebral palsy. Physical examination revealed ataxia, oculomotor apraxia, extrapyramidal signs, and a wide-based, shuffling gait. Magnetic resonance imaging showed vermian aplasia, consistent with Joubert syndrome. Positron emission tomography scan revealed normal fluorodopa uptake, but elevated raclopride binding, compatible with dopamine deficiency. This case demonstrates that a patient with Joubert syndrome may survive into adulthood and present as a chronic neurologic disorder with subacute extrapyramidal signs.

Novel features in a patient homozygous for the L347P mutation in the PINK1 gene

The purpose of this study was to assess the genotype-phenotype of PINK1 mutations. We genotyped eight known mutations in three clinic-based cohorts with Parkinsonism and found one homozygous p.L347P mutation in PINK1. Clinically, hypo-osmia and profound diurnal variation of symptoms were identified as novel features; fluorodopa positron emission tomography revealed striking decline in striatal fluorodopa uptake. We suggest that it may be possible to clinically separate this form of Parkinsonism from dopa-responsive dystonia and Parkin-related Parkinsonism. Furthermore, as this mutation has only been reported in Filipinos (two originated from Luzon island), our results support the hypothesis of a common founder.

18F]FDOPA PET as an endophenotype for Parkinson's Disease linkage studies

Parkinson disease (PD) is a late onset disorder with age-dependent penetrance that may confound genetic studies, since affected individuals may not demonstrate clinical manifestations at the time of evaluation. The use of endophenotypes, biologic surrogates for clinical disease diagnoses, may permit more accurate classification of at-risk subjects. Positron emission tomography (PET) measurements of 6-[18F]fluorodopa ([18F]FDOPA) uptake indicate nigrostriatal neuronal integrity and may provide a useful endophenotype for PD linkage studies. We performed [18F]FDOPA PET in 11 members of a large, multi-incident Amish family with PD, 24 normals and 48 people with clinically definite idiopathic PD (PD controls). Clinical diagnoses in the Amish were clinically definite PD in four, clinically probable in one, clinically possible in five, and normal in one. Abnormal [18F]FDOPA posterior putamen uptake was defined as less than 3 standard deviations below the normal mean. The criteria were applied to the Amish sample to determine a PET endophenotype for each. We performed genetic simulations using SLINK to model the effect phenoconversion with the PET endophenotype had on logarithm of odds (LOD) scores. PET endophenotype confirmed the status of two clinically definite subjects. Two clinically definite Amish PD subjects had normal PETs. Two possible PD were converted to "PET definite PD." The remainder had normal PETs. The average maximum LOD score with the pre-PET was 6.14 +/- 0.84. Simulating phenoconversion of subjects with unknown phenotypes increased the LOD score to 7.36 +/- 1.23. The [18F]FDOPA PET endophenotype permits phenoconversion in multi-incident PD families and may increase LOD score accuracy and power of an informative pedigree.

Profile of families with parkinsonism-predominant spinocerebellar ataxia type 2 (SCA2).

Spinocerebellar ataxia type 2 (SCA2) has been recognized recently as an uncommon cause of parkinsonism, an alternate presentation to the typical cerebellar disorder. This research review summarizes the existing literature on parkinsonism-predominant presentation SCA2 and presents new clinical cases of patients with this condition. Various phenotypes are noted in this subtype of SCA2, including parkinsonism indistinguishable from idiopathic Parkinson's disease (PD), parkinsonism plus ataxia, motor neuron disease, and postural tremor. In several kindreds with multiple affected family members, the SCA2 expansion segregated with disease; in addition, several single cases of parkinsonism with and without a family history are also described. The number of repeats in symptomatic patients ranged from 33 to 43. Interruption of the CAG repeat with CAA, CGG, or CCG was found in some individuals, possibly stabilizing the repeat structure and accounting for the relative stability of the repeat size across generations in some families; allele length is not necessarily indicative of trinucleotide repeat architecture. Positron emission tomography scanning in one family showed reduced fluorodopa uptake and normal to increased raclopride binding with a rostrocaudal gradient similar to that found in idiopathic PD. This review emphasizes the importance of testing for SCA2 in patients with parkinsonism and a family history of neurodegenerative disorders. Testing for SCA2 is also important in studies of inherited parkinsonism.

Presynaptic dopaminergic dysfunction in schizophrenia: a positron emission tomographic [18F]fluorodopa study.

The dopamine overactivity hypothesis of schizophrenia remains one of the most influential theories of the pathophysiology of the illness. Radiotracer brain imaging studies are now directly testing aspects of the overactivity hypothesis. To assess presynaptic dopaminergic function in a large cohort of patients with schizophrenia by means of [18F]fluorodopa uptake and a high-sensitivity 3-dimensional positron emission tomograph. We predicted elevations in striatal [18F]fluorodopa uptake and reductions in prefrontal cortical [18F]fluorodopa uptake in patients with schizophrenia. Case-control study. Research institute investigation recruiting hospital outpatients. Sixteen male medicated hospital outpatients with a DSM-IV diagnosis of schizophrenia (mean age, 38 years) and 12 age-matched male volunteers free of psychiatric and neurologic illness. [18F]fluorodopa positron emission tomographic scanning. MAIN OUTDOME MEASURE: [18F]fluorodopa uptake constant Ki measured with statistical parametric mapping and region-of-interest analyses. Statistical parametric mapping (P<.05 corrected) and region-of-interest analyses (P<.01) showed increased [18F]fluorodopa uptake, confined primarily to the ventral striatum in patients with schizophrenia. No reductions in prefrontal cortical [18F]fluorodopa uptake Ki were seen in the statistical parametric mapping and region-of-interest analyses, although dorsal anterior cingulate [18F]fluorodopa Ki correlated with performance on the Stroop Color-Word Test in both groups. As in studies in unmedicated patients, presynaptic striatal dopamine dysfunction is present in medicated schizophrenic patients, adding further in vivo support for dopamine overactivity in the illness.