PubMed Health⌕ Search

Biomedical subjects

Anne Lingford-Hughes

Publications and source records attributed to Anne Lingford-Hughes.

10 recordsLinked to original sources
PubMed2006

Opioid imaging.

Many breakthrough scientific discoveries have been made using opioid imaging, particularly in the fields of pain, addiction and epilepsy research. Recent developments include the application of ever higher resolution whole-brain positron emission tomography (PET) scanners, the availability of several radioligands, the combination of PET with advanced structural imaging, advances in modeling macroparameters of PET ligand binding, and large-scale statistical analysis of imaging datasets. Suitable single-photon emission computed tomography (SPECT) tracers are lacking, but with the increase in the number of available PET (or PET/CT) cameras and cyclotrons thanks to the clinical successes of PET in oncology, PET may become widespread enough to overcome this limitation. In the coming decade, we hope to see a more widespread application of the techniques developed in healthy volunteers to patients and more clinical impact of opioid imaging.

Brain↗
PubMed2005

Is there cognitive impairment in clinically 'healthy' abstinent alcohol dependence?

AIMS: The aim of this study was to determine neuropsychological performance in apparently cognitively, mentally, and physically healthy abstinent alcohol-dependent subjects compared with control subjects who were recruited for a number of different neuroimaging studies. METHODS: All subjects completed a battery of neuropsychological tests as part of the neuroimaging protocol. RESULTS: The group dependent on alcohol performed as well as controls on a non-verbal memory test and verbal fluency but performed worse in the verbal memory task, Trail A + B, and total IQ derived from Silverstein's short-form of the WAIS-R. However, the IQ performance of both groups was above average. In both groups, age was associated with slower performance on the Trail A + B task. In the alcohol-dependent group, severity of dependence and length of abstinence was not associated with performance of any task. CONCLUSIONS: In this apparently clinically healthy population of abstinent alcohol-dependent subjects, frontal lobe dysfunction was detectable using the Trail A + B and digit symbol tasks. This was despite above-average WAIS-R IQ scores. Consideration needs to be given to routine incorporation of cognitive testing in alcohol dependence since subtle deficits may not be easily apparent and may impact on treatment outcome.

Adult↗
PubMed2005

Human brain imaging and substance abuse.

Over the past decade, functional neuroimaging has contributed greatly to our knowledge about the neuropharmacology of substance misuse in man. Techniques such as functional magnetic resonance imaging, positron emission tomography (PET) or single photon emission tomography (SPET) can measure changes in regional cerebral activity, whereas changes in neuropharmacological parameters (e.g. receptor number and neurotransmitter levels) can be directly measured only with PET and SPET. Recently, a series of studies have shown common effects of substances of misuse on the brain, such as an acute increase in dopamine release (followed by hypofunction after chronic use) and cue exposure-induced activation of the frontal cortex, as well as specific effects, such as ecstasy-induced decreases in serotonergic transporters and occupancy of opiate receptors by substitute drugs (e.g. methadone and buprenorphine) in opiate addicts.

Brain↗
PubMed2005

Human functional neuroimaging connectivity research in dependence.

Functional and effective connectivity are relatively new techniques in the analysis of functional neuroimaging studies in humans. They have previously been used in studies of 'normal' psychological and neurological processes such as vision before gradually transferring into use in pathological disease states such as schizophrenia. These techniques are now beginning to extend into the field of substance misuse and dependence. So far, most functional neuroimaging studies in this field have shown consistent patterns of activation in several brain regions, and theories are emerging based upon these and animal models. Studies of brain connectivity can now begin to help further unravel the tangle of disparate brain regions and their connections that underpin the psychopharmacological processes of dependence.

Brain↗
PubMed2004

Using [11C]diprenorphine to image opioid receptor occupancy by methadone in opioid addiction: clinical and preclinical studies.

Substitute methadone prescribing is one of the main modes of treatment for opioid dependence with established evidence for improved health and social outcomes. However, the pharmacology underpinning the effects of methadone is little studied despite controversies about dosing in relation to outcome. We therefore examined the relationship between methadone dose and occupation of opioid receptors in brain using the positron emission tomography (PET) radioligand [(11)C]diprenorphine in humans and rats. Eight opioid-dependent subjects stable on their substitute methadone (18-90 mg daily) had an [(11)C]diprenorphine PET scan at predicted peak plasma levels of methadone. These were compared with eight healthy controls. No difference in [(11)C]diprenorphine binding was found between the groups, with no relationship between methadone dose and occupancy. Adult male Sprague-Dawley rats that had been given an acute i.v. injection of methadone hydrochloride (0.35, 0.5, 0.7, or 1.0 mg kg(-1)) before [(11)C]diprenorphine showed a dose-dependent increase in biodistribution but no reduction in [(11)C]diprenorphine binding. We suggest that the lack of a dose-dependent relationship between methadone dose, either given chronically in human or acutely in rat, and occupancy of opioid receptor measured with [(11)C]diprenorphine PET is related to efficacy of this opioid agonist at very low levels of opioid receptor occupancy. This has implications for understanding the actions of methadone in comparison with other opioid drugs such as partial agonists and antagonists.

Adult↗
PubMed2003

Functional connectivity analysis of the neural circuits of opiate craving: "more" rather than "different"?

We investigated the functional connectivity of brain regions activated during opiate craving. Previously we used recorded autobiographical scripts to induce opiate craving in 12 abstinent opiate-dependent subjects while they were undergoing positron emission tomography (PET) scanning using the regional cerebral blood flow (rCBF) tracer H2 15O. SPM99 was used to examine the connectivity patterns associated with the primary brain regions activated in response to drug-craving memories (anterior cingulate, AC) and correlated with opiate craving (orbitofrontal cortex, OFC). Two separate connectivity patterns were identified associated with the OFC and AC regions. The AC region was associated with activity in the left temporal region. The left OFC region activity correlated with activity in the right OFC, and left parietal and posterior insular regions. There was also a positive association with the hippocampus and brainstem. Both the AC and OFC regions showed a negative association with posterior visual areas. We suggest that the patterns of functional connectivity reflect the ability of drug-related stimuli to activate attentional and memory circuits to a greater degree than non-drug-related stimuli. This argues that neural circuits of dependence and craving are not specific "craving" or "addiction" brain regions but are "normal" circuits activated to a greater degree.

Brain Stem↗
PubMed2003

A pilot study on the effects of treatment with acamprosate on craving for alcohol in alcohol-dependent patients.

This study investigated the effects of treatment with acamprosate on craving for alcohol by using a contextual priming task with alcohol and neutral words and craving questionnaires (ACQ, OCDS) in alcohol-dependent patients who abstained from alcohol for 6 weeks. The acamprosate-treated group (n = 16) were given 666 mg t.d.s. with standard group-work aimed at abstinence. The unmedicated control group (n = 13) received only standard group therapy. The results showed that the acamprosate treated group was faster in their responses to craving-related stimuli and scored lower on craving questionnaires during week 6 compared with week 2. Our results suggest that acamprosate may play a role in reduction of craving for alcohol after 6 weeks of treatment.

Acamprosate↗
PubMed2002

Imaging the GABA-benzodiazepine receptor subtype containing the alpha5-subunit in vivo with [11C]Ro15 4513 positron emission tomography.

There is evidence of marked variation in the brain distribution of specific subtypes of the GABA-benzodiazepine receptor and that particular subtypes mediate different functions. The alpha5-containing subtype is highly expressed in the hippocampus, and selective alpha5 inverse agonists (which decrease tonic GABA inhibition) are being developed as potential memory-enhancing agents. Evidence for such receptor localization and specialization in humans in vivo is lacking because the widely used probes for imaging the GABA-benzodiazepine receptors, [11C]flumazenil and [123I]iomazenil, appear to reflect binding to the alpha1 subtype, based on its distribution and affinity of flumazenil for this subtype. The authors characterized for positron emission tomography (PET) a radioligand from Ro15 4513, the binding of which has a marked limbic distribution in the rat and human brain in vivo. Competition studies in vivo in the rat revealed that radiolabeled Ro15 4513 uptake was reduced to nonspecific levels only by drugs that have affinity for the alpha5 subtype (flunitrazepam, RY80, Ro15 4513, L655,708), but not by the alpha1 selective agonist, zolpidem. Quantification of [11C]Ro15 4513 PET was performed in humans using a metabolite-corrected plasma input function. [11C]Ro15 4513 uptake was relatively greater in limbic areas compared with [11C]flumazenil, but lower in the occipital cortex and cerebellum. The authors conclude that [11C]Ro15 4513 PET labels in vivo the GABA-benzodiazepine receptor containing the alpha5 subtype in limbic structures and can be used to further explore the functional role of this subtype in humans.

Animals↗