Publications
156 results found
Saleem A, Searle GE, Kenny LM, et al., 2017, Lapatinib access into normal brain and brain metastases in patients with Her-2 overexpressing breast cancer (vol 5, 30, 2015), EJNMMI RESEARCH, Vol: 7, ISSN: 2191-219X
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- Citations: 1
Saleem A, Searle GE, Kenny LM, et al., 2017, Erratum to: Lapatinib access into normal brain and brain metastases in patients with Her-2 overexpressing breast cancer., EJNMMI Research, Vol: 7, Pages: 74-74, ISSN: 2191-219X
Femminella G, Dani M, Wood M, et al., 2017, Microglial activation is associated with higher grey matter density and hippocampal volume in MCi subjects, Alzheimer's and Dementia, Vol: 13, Pages: P921-P921, ISSN: 1552-5260
Habib M, Mak E, Gabel S, et al., 2017, Functional neuroimaging findings in healthy middle-aged adults at risk of Alzheimer's disease, AGEING RESEARCH REVIEWS, Vol: 36, Pages: 88-104, ISSN: 1568-1637
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- Citations: 32
Mak E, Gabel S, Mirette H, et al., 2017, Structural neuroimaging in preclinical dementia: From microstructural deficits and grey matter atrophy to macroscale connectomic changes, AGEING RESEARCH REVIEWS, Vol: 35, Pages: 250-264, ISSN: 1568-1637
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- Citations: 38
Chhabra S, Underwood J, Cole JH, et al., 2017, Clinical research cerebral MRI findings in HIV positive subjects and appropriate controls, BHIVA annual conference, Publisher: WILEY, Pages: 10-10, ISSN: 1464-2662
Kalk NJ, Guo Q, Owen D, et al., 2017, Decreased hippocampal translocator protein (18 kDa) expression in alcohol dependence: a [(11)C]PBR28 PET study, Translational Psychiatry, Vol: 7, ISSN: 2158-3188
Repeated withdrawal from alcohol is clinically associated with progressive cognitive impairment. Microglial activation occurring during pre-clinical models of alcohol withdrawal is associated with learning deficits. We investigated whether there was microglial activation in recently detoxified alcohol-dependent patients (ADP), using [(11)C]PBR28 positron emission tomography (PET), selective for the 18kDa translocator protein (TSPO) highly expressed in activated microglia and astrocytes. We investigated the relationship between microglial activation and cognitive performance. Twenty healthy control (HC) subjects (45±13; M:F 14:6) and nine ADP (45±6, M:F 9:0) were evaluated. Dynamic PET data were acquired for 90 min following an injection of 331±15 MBq [(11)C]PBR28. Regional volumes of distribution (VT) for regions of interest (ROIs) identified a priori were estimated using a two-tissue compartmental model with metabolite-corrected arterial plasma input function. ADP had an ~20% lower [(11)C]PBR28 VT, in the hippocampus (F(1,24) 5.694; P=0.025), but no difference in VT in other ROIs. Hippocampal [(11)C]PBR28 VT was positively correlated with verbal memory performance in a combined group of HC and ADP (r=0.720, P<0.001), an effect seen in HC alone (r=0.738; P=0.001) but not in ADP. We did not find evidence for increased microglial activation in ADP, as seen pre-clinically. Instead, our findings suggest lower glial density or an altered activation state with lower TSPO expression. The correlation between verbal memory and [(11)C]PBR28 VT, raises the possibility that abnormalities of glial function may contribute to cognitive impairment in ADP.
Limbrick-Oldfield E, Mick I, Cocks R, et al., 2017, Neural substrates of cue reactivity and craving in gambling disorder, Translational Psychiatry, Vol: 7, ISSN: 2158-3188
Cue reactivity is an established procedure in addictions research for examining the subjective experience and neural basis of craving. This experiment sought to quantify cue-related brain responses in Gambling Disorder using personally tailored cues in conjunction with subjective craving, as well as a comparison with appetitive non-gambling stimuli. Participants with Gambling Disorder (n=19) attending treatment and 19 controls viewed personally tailored blocks of gambling-related cues, as well as neutral cues and highly appetitive (food) images during a functional MRI scan performed ~2-3 hours after a usual meal. fMRI analysis examined cue-related brain activity, cue-related changes in connectivity, and associations with block-by-block craving ratings. Craving ratings in the participants with Gambling Disorder increased following gambling cues compared with non-gambling cues. fMRI analysis revealed group differences in left insula and anterior cingulate cortex, with the Gambling Disorder group showing greater reactivity to the gambling cues, but no differences to the food cues. In participants with Gambling Disorder, craving to gamble correlated positively with gambling cue-related activity in the bilateral insula and ventral striatum, and negatively with functional connectivity between the ventral striatum and the medial PFC. Gambling cues, but not food cues, elicit increased brain responses in reward-related circuitry in individuals with Gambling Disorder (compared to controls), providing support for the incentive sensitisation theory of addiction. Activity in the insula co-varied with craving intensity, and may be a target for interventions.
Carswell C, Muckle K, Waldman A, et al., 2016, FLORBETAPIR IMAGING IN CLINICAL PRACTICE: A RETROSPECTIVE STUDY OF 100 PATIENTS, Annual Meeting of the Association-of-British-Neurologists (ABN), Publisher: BMJ PUBLISHING GROUP, ISSN: 0022-3050
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- Citations: 2
Newbould R, Muraro P, Bishop C, et al., 2016, Analysis of ageing-associated grey matter volume in patients with multiple sclerosis shows excess atrophy in subcortical regions, NeuroImage-Clinical, Vol: 13, Pages: 9-15, ISSN: 2213-1582
Age of onset in multiple sclerosis (MS) exerts an influence on the course of disease. This study examined whether global and regional brain volumes differed between “younger” and “older” onset MS subjects who were matched for short disease duration, mean 1.9 years and burden as measured by the MS Severity Score and relapses.21 younger-onset MS subjects (age 30.4 ± 3.2 years) were compared with 17 older-onset (age 48.7 ± 3.3 years) as well as age-matched controls (n = 31, 31.9 ± 3.5 years and n = 21, 47.3 ± 4.0 years). All subjects underwent 3D volumetric T1 and T2-FLAIR imaging. White matter (WM) and grey matter (GM) lesions were outlined manually. Lesions were filled prior to tissue and structural segmentation to reduce classification errors.Volume loss versus control was predominantly in the subcortical GM, at > 13% loss. Younger and older-onset MS subjects had similar, strong excess loss in the putamen, thalamus, and nucleus accumbens. No excess loss was detected in the amygdala or pallidum. The hippocampus and caudate showed significant excess loss in the younger group (p < 0.001) and a strong trend in the older-onset group.These results provide a potential imaging correlate of published neuropsychological studies that reported the association of younger age at disease onset with impaired cognitive performance, including decreased working memory.
De Simoni S, Grover PJ, Jenkins PO, et al., 2016, Disconnection between the default mode network and medial temporal lobes in post-traumatic amnesia, Brain, Vol: 139, Pages: 3137-3150, ISSN: 0006-8950
Post-traumatic amnesia is very common immediately after traumatic brain injury. It is characterised by a confused, agitated state and a pronounced inability to encode new memories and sustain attention. Clinically, post-traumatic amnesia is an important predictor of functional outcome. However, despite its prevalence and functional importance, the pathophysiology of post-traumatic amnesia is not understood. Memory processing relies on limbic structures such as the hippocampus, parahippocampus and parts of the cingulate cortex. These structures are connected within an intrinsic connectivity network, the Default Mode Network. Interactions within the Default Mode Network can be assessed using resting state functional magnetic resonance imaging, which can be acquired in confused patients unable to perform tasks in the scanner. Here we used this approach to test the hypothesis that the mnemonic symptoms of post-traumatic amnesia are caused by functional disconnection within the Default Mode Network. We assessed whether the hippocampus and parahippocampus showed evidence of transient disconnection from cortical brain regions involved in memory processing. 19 traumatic brain injury patients were classified into post-traumatic amnesia and traumatic brain injury control groups, based on their performance on a paired associates learning task. Cognitive function was also assessed with a detailed neuropsychological test battery. Functional interactions between brain regions were investigated using resting-state functional magnetic resonance imaging. Together with impairments in associative memory patients in post-traumatic amnesia demonstrated impairments in information processing speed and spatial working memory. Patients in post-traumatic amnesia showed abnormal functional connectivity between the parahippocampal gyrus and posterior cingulate cortex. The strength of this functional connection correlated with both associative memory and information processing speed and normal
Mick I, Ramos C, Myers J, et al., 2016, Evidence for GABA-A receptor dysregulation in gambling disorder: correlation with impulsivity., Addiction Biology, Vol: 22, Pages: 1601-1609, ISSN: 1369-1600
Background: As a behavioral addiction, gambling disorder (GD) provides an opportunity to characterize addictive processes without the potentially confounding effects of chronic excessive drug and alcohol exposure. Impulsivity is an established precursor to such addictive behaviours and GD is associated with greater impulsivity. There is also evidence of GABAergic dysregulation in substance addiction and in impulsivity. Methods: This study therefore investigated GABAA receptor availability in 15 individuals with GD and 19 healthy volunteers (HV) using [11C]Ro15-4513, a relatively selective α5 benzodiazepine receptor PET tracer and its relationship with impulsivity. Results: We found significantly higher [11C]Ro15-4513 total distribution volume (VT) in the right hippocampus in the GD group compared with HV. We found higher levels of The ‘Negative Urgency’ construct of impulsivity in GD and these were positively associated with higher [11C]Ro15-4513 VT in the amygdala in the GD group; no such significant correlations were evident in the HV group. Conclusions: These results contrast with reduced binding of GABAergic PET ligands described previously in alcohol and opiate addiction and add to growing evidence for distinctions in the neuropharmacology between substance and behavioral addictions. These results provide the first characterization of GABAA receptors in GD with [11C]Ro15-4513 PET and show greater α5 receptor availability and positive correlations with trait impulsivity. This GABAergic dysregulation is potential target for treatment.
McGonigle J, Murphy A, Paterson LM, et al., 2016, The ICCAM platform study: An experimental medicine platform for evaluating new drugs for relapse prevention in addiction. Part B: fMRI description, Journal of Psychopharmacology, Vol: 31, Pages: 3-16, ISSN: 1461-7285
OBJECTIVES: We aimed to set up a robust multi-centre clinical fMRI and neuropsychological platform to investigate the neuropharmacology of brain processes relevant to addiction - reward, impulsivity and emotional reactivity. Here we provide an overview of the fMRI battery, carried out across three centres, characterizing neuronal response to the tasks, along with exploring inter-centre differences in healthy participants. EXPERIMENTAL DESIGN: Three fMRI tasks were used: monetary incentive delay to probe reward sensitivity, go/no-go to probe impulsivity and an evocative images task to probe emotional reactivity. A coordinate-based activation likelihood estimation (ALE) meta-analysis was carried out for the reward and impulsivity tasks to help establish region of interest (ROI) placement. A group of healthy participants was recruited from across three centres (total n=43) to investigate inter-centre differences. PRINCIPLE OBSERVATIONS: The pattern of response observed for each of the three tasks was consistent with previous studies using similar paradigms. At the whole brain level, significant differences were not observed between centres for any task. CONCLUSIONS: In developing this platform we successfully integrated neuroimaging data from three centres, adapted validated tasks and applied whole brain and ROI approaches to explore and demonstrate their consistency across centres.
Grech-Sollars M, Ordidge KL, Vaqas B, et al., 2016, <SUP>18</SUP>F-fluoromethylcholine (FMC) PET/CT and proton magnetic resonance spectroscopy; imaging and tissue biomarkers of cell membrane turnover in primary brain gliomas - a pilot study, Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), Publisher: SPRINGER, Pages: S195-S195, ISSN: 1619-7070
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Grover VP, Southern L, Dyson JK, et al., 2016, Early Primary Biliary Cholangitis is Characterised by Brain Abnormalities on Cerebral Magnetic Resonance Imaging, Alimentary Pharmacology & Therapeutics, Vol: 44, Pages: 936-945, ISSN: 1365-2036
Background: Brain change can occur in primary biliary cholangitis (PBC), potentially as a result of cholestatic and/or inflammatory processes. This change is linked to systemic symptoms of fatigue and cognitive impairment. Aim: To identify whether brain change occurs early in PBC. If the change develops early and is progressive, it may explain the difficulty in treating these symptoms. Methods: Early disease brain change was explored in 13 patients with newly diagnosed biopsy-proven pre-cirrhotic PBC using magnetization transfer, diffusion-weighted imaging and 1H magnetic resonance spectroscopy. Results were compared to 17 healthy volunteers. Results: Cerebral magnetization transfer ratios were reduced in early PBC, compared to healthy volunteers, in the thalamus, putamen and head of caudate with no greater reduction in patients with greater symptom severity. Mean apparent diffusion coefficients were increased in the thalamus only. No 1H magnetic resonance spectroscopy abnormalities were seen. Serum manganese levels were elevated in all PBC patients, but no relationship was seen with imaging or symptom parameters. There were no correlations between neuroimaging data, laboratory data, symptom severity scores or age. Conclusions: This is the first study to be performed in this pre-cirrhotic patient population and we have highlighted that neuroimaging changes are present at a much earlier stage than previously demonstrated. The neuroimaging abnormalities suggest that the brain changes seen in PBC occur early in the pathological process, even before significant liver damage has occurred. If such changes are linked to symptom pathogenesis, this could have important implications for the timing of second-line-therapy use.
Lema A, Bishop C, Malik O, et al., 2016, A compararison of magnetization transfer methods to assess brain and cervical cord microstructure in multiple sclerosis, Journal of Neuroimaging, Vol: 27, Pages: 221-226, ISSN: 1552-6569
BACKGROUND: Demyelination is a core pathological feature of multiple sclerosis (MS) and spontaneous remyelination appears to be an important mechanism for repair in the disease. Magnetization transfer ratio imaging (MTR) has been used extensively to evaluate demyelination, although limitations to its specificity are recognized. MT saturation imaging (MTsat) removes some of the T1 dependence of MTR. We have performed a comparative evaluation of MTR and MTsat imaging in a mixed group of subjects with active MS, to explore their relative sensitivity to pathology relevant to explaining clinical outcomes. METHODS: A total of 134 subjects underwent MRI of their brain and cervical spinal cord. Isotropic 3-dimensional pre- and postcontrast T1-weighted and T2-weighted fluid-attenuated inversion recovery (FLAIR) volumes were segmented into brain normal appearing white matter (NAWM), brain WM lesions (WML), normal appearing spinal cord (NASC), and spinal cord lesions. Volumes and metrics for MTR and MTsat histograms were calculated for each region. RESULTS: Significant Spearman correlations were found with the Expanded Disability Status Scale and timed 25-foot walk for the whole brain and WML MTR, but not in that from the NAWM or any cervical spinal cord region. By contrast, the MTsat was correlated with both disability metrics in all these regions in both the brain and spine. CONCLUSIONS: This study extends prior work relating atrophy and lesion load with disability, by characterization of MTsat parameters. MTsat is practical in routine clinical applications and may be more sensitive to tissue damage than MTR for both brain and cervical spinal cord.
Grover VP, McPhail M, Wylezinska M, et al., 2016, A longitudinal study of patients with cirrhosis treated with L-ornithine L-aspartate, examined with magnetization transfer, diffusion-weighted imaging and magnetic resonance spectroscopy, Metabolic Brain Disease, Vol: 32, Pages: 77-86, ISSN: 1573-7365
The presence of overt hepatic encephalopathy (HE) is associated with structural, metabolic and functional changes in the brain discernible by use of a variety of magnetic resonance (MR) techniques. The changes in patients with minimal HE are less well documented. Twenty-two patients with well-compensated cirrhosis, seven of whom had minimal HE, were examined with cerebral 3 Tesla MR techniques, including T1- and T2-weighted, magnetization transfer and diffusion-weighted imaging and proton magnetic resonance spectroscopy sequences. Studies were repeated after a 4-week course of oral L-ornithine L-aspartate (LOLA). Results were compared with data obtained from 22 aged-matched healthy controls. There was no difference in mean total brain volume between patients and controls at baseline. Mean cerebral magnetization transfer ratios were significantly reduced in the globus pallidus and thalamus in the patients with cirrhosis irrespective of neuropsychiatric status; the mean ratio was significantly reduced in the frontal white matter in patients with minimal HE compared with healthy controls but not when compared with their unimpaired counterparts. There were no significant differences in either the median apparent diffusion coefficients or the mean fractional anisotropy, calculated from the diffusion-weighted imaging, or in the mean basal ganglia metabolite ratios between patients and controls. Psychometric performance improved in 50% of patients with minimal HE following LOLA, but no significant changes were observed in brain volumes, cerebral magnetization transfer ratios, the diffusion weighted imaging variables or the cerebral metabolite ratios. MR variables, as applied in this study, do not identify patients with minimal HE, nor do they reflect changes in psychometric performance following LOLA.
Femminella G, Dani M, Fan Z, et al., 2016, Does neuroinflammation predate amyloid formation in subjects at risk for Alzheimer’s disease?, Alzheimer's and Dementia, Vol: 12, Pages: P283-P283, ISSN: 1552-5260
Fan Z, Edison P, Atkinson R, et al., 2016, Flutriciclamide ([18F]GE180) PET: first in human PET study of novel in vivo marker of human translator protein, Alzheimer's and Dementia, Vol: 12, Pages: P397-P397, ISSN: 1552-5260
Fan Z, Calsolaro V, Atkinson R, et al., 2016, Flutriciclamide (18F-GE180) PET: first in human PET study of novel 3rd generation in vivo marker of human translator protein., Journal of Nuclear Medicine, Vol: 57, Pages: 1753-1759, ISSN: 1535-5667
Neuroinflammation is associated with neurodegenerative disease. PET (positron emission tomography) radioligands targeting the 18 kDa translocator protein (TSPO) has been used as in vivo markers of neuroinflammation, but there is an urgent need for novel probes with improved signal-to-noise ratio. Flutriciclamide ((18)F-GE180) is a recently developed third generation TSPO ligand. In this first study, we evaluated the optimum scan duration and kinetic modelling strategies for (18)F-GE180 PET in (older) healthy controls (HC). METHODS: Ten HC, six TSPO high affinity binders (HABs) and four mixed affinity binders (MABs), were recruited. All subjects had detailed neuropsychological tests, MRI and a 210 min (18)F-GE180 dynamic PET/CT scan using metabolite corrected arterial plasma input function. We evaluated five different kinetic models: irreversible and reversible two-tissue compartment models, a reversible one-tissue model and two models with an extra irreversible vascular compartment. The optimum scan length was investigated based on 210 min scan data. The feasibility of generating parametric maps was also investigated using graphical analysis. RESULTS: (18)F-GE180 concentration was higher in plasma than in whole blood during the entire scan duration. Using the kinetic model, the volume of distribution (VT) was 0.17 in HABs and 0.12 in MABs. The model that best represented brain (18)F-GE180 kinetics across regions was the reversible two-tissue compartment model (2TCM4k) and 90 min resulted as the optimum scan length required to obtain stable estimates. Logan graphical analysis with arterial input function gave a VT highly consistent with VT in kinetic model, which could be used for voxel-wise analysis. CONCLUSION: We report for the first time the kinetic properties of the novel third generation TSPO PET ligand, (18)F-GE180, in humans: 2TCM4k is the optimal method to quantify the brain uptake, 90 min is the optimal scan length and Logan approach could be used to genera
Mouchlianitis E, Bloomfield MAP, Law V, et al., 2016, Treatment-Resistant Schizophrenia Patients Show Elevated Anterior Cingulate Cortex Glutamate Compared to Treatment-Responsive, SCHIZOPHRENIA BULLETIN, Vol: 42, Pages: 744-752, ISSN: 0586-7614
Limbrick-Oldfield E, Mick I, Cocks R, et al., 2016, Neural Substrates of Cue Reactivity and Craving in Gambling Disorder, Publisher: ELSEVIER SCIENCE INC, Pages: 341S-341S, ISSN: 0006-3223
Booth TC, Ashkan K, Brazil L, et al., 2016, Re: Tumour progression or pseudoprogression? A review of post-treatment radiological appearances of glioblastoma, CLINICAL RADIOLOGY, Vol: 71, Pages: 495-496, ISSN: 0009-9260
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- Citations: 4
Mick I, Myers J, Ramos AC, et al., 2016, Blunted Endogenous Opioid Release Following an Oral Amphetamine Challenge in Pathological Gamblers, 3rd International Conference on Behavioral Addictions, Publisher: Akadémiai Kiadó, Pages: 30-30, ISSN: 2063-5303
Matthews PM, Roncaroli F, Waldman A, et al., 2016, A practical review of the neuropathology and neuroimaging of multiple sclerosis, Practical Neurology, Vol: 16, Pages: 279-287, ISSN: 1474-7766
The variability in the severity and clinical course of multiple sclerosis (MS) has as its basis an extreme heterogeneity in the location, nature and extent of pathology in the brain and spinal cord. Understanding the underlying neuropathology and associated pathogenetic mechanisms of the disease helps to communicate the rationale for treatment and disease monitoring to patients. Neuroimaging is an important tool for this: it allows clinicians to relate neuropathological changes to clinical presentations and to monitor the course of their disease. Here, we review MS neuropathology and its imaging correlates to provide a practical guide for using MRI to assess disease severity and treatment responses. This provides a foundation for optimal management of patients based on the principle that they show 'no evidence of disease activity'.
Taylor EM, Murphy A, Boyapati V, et al., 2016, Impulsivity in abstinent alcohol and polydrug dependence: a multidimensional approach, Psychopharmacology, Vol: 233, Pages: 1487-1499, ISSN: 1432-2072
Grech-Sollars M, Vaqas B, Thompson G, et al., 2015, NIMG-30an MRS and PET guided biopsy tool for ultrasound-based intra-operative neuro-navigational systems, Neuro-Oncology, Vol: 17, Pages: v160.2-v160, ISSN: 1522-8517
Wardlaw JM, Davies H, Booth TC, et al., 2015, Acting on incidental findings in research imaging, BMJ-BRITISH MEDICAL JOURNAL, Vol: 351, ISSN: 0959-535X
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- Citations: 29
Ordidge K, Grech-Sollars M, Honeyfield L, et al., 2015, 18F-FLUOROMETHYLCHOLINE (18F-FMC) PET/CT AND MAGNETIC RESONANCE SPECTROSCOPY (MRS) IMAGING AND TISSUE BIOMARKERS OF CELL MEMBRANE TURNOVER IN PRIMARY BRAIN GLIOMAS-A PILOT STUDY, Meeting of the British-Neuro-Oncology-Society (BNOS), Publisher: OXFORD UNIV PRESS INC, Pages: 5-5, ISSN: 1522-8517
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- Citations: 1
Lingford-Hughes AR, Mick I, Myers J, et al., 2015, Blunted endogenous opioid release following an oral amphetamine challenge in pathological gamblers, Neuropsychopharmacology, Vol: 41, Pages: 1742-1750, ISSN: 1740-634X
Pathological gambling is a psychiatric disorder and the first recognized behavioral addiction, with similarities to substance use disorders but without the confounding effects of drug-related brain changes. Pathophysiology within the opioid receptor system is increasingly recognized in substance dependence, with higher mu-opioid receptor (MOR) availability reported in alcohol, cocaine and opiate addiction. Impulsivity, a risk factor across the addictions, has also been found to be associated with higher MOR availability. The aim of this study was to characterize baseline MOR availability and endogenous opioid release in pathological gamblers (PG) using [¹¹C]carfentanil PET with an oral amphetamine challenge. 14 PG and 15 healthy volunteers (HV) underwent two [¹¹C]carfentanil PET scans, before and after an oral administration of 0.5 mg/kg of d-amphetamine. The change in [¹¹C]carfentanil binding between baseline and post-amphetamine scans (ΔBPND) was assessed in 10 regions of interest (ROI). MOR availability did not differ between PG and HV groups. As seen previously, oral amphetamine challenge led to significant reductions in [¹¹C]carfentanil BPND in 8/10 ROI in HV. PG demonstrated significant blunting of opioid release compared with HV. PG also showed blunted amphetamine-induced euphoria and alertness compared with HV. Exploratory analysis revealed that impulsivity positively correlated with caudate baseline BPND in PG only. This study provides the first evidence of blunted endogenous opioid release in PG. Our findings are consistent with growing evidence that dysregulation of endogenous opioids may play an important role in the pathophysiology of addictions.
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