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  1. Article ; Online: An open-source pipeline for analysing changes in microglial morphology.

    Clarke, Devin / Crombag, Hans S / Hall, Catherine N

    Open biology

    2021  Volume 11, Issue 8, Page(s) 210045

    Abstract: Changes in microglial morphology are powerful indicators of the inflammatory state of the brain. Here, we provide an open-source microglia morphology analysis pipeline that first cleans and registers images of microglia, before extracting 62 parameters ... ...

    Abstract Changes in microglial morphology are powerful indicators of the inflammatory state of the brain. Here, we provide an open-source microglia morphology analysis pipeline that first cleans and registers images of microglia, before extracting 62 parameters describing microglial morphology. It then compares control and 'inflammation' training data and uses dimensionality reduction to generate a single metric of morphological change (an 'inflammation index'). This index can then be calculated for test data to assess inflammation, as we demonstrate by investigating the effect of short-term high-fat diet consumption in heterozygous Cx3CR1-GFP mice, finding no significant effects of diet. Our pipeline represents the first open-source microglia morphology pipeline combining semi-automated image processing and dimensionality reduction. It uses free software (ImageJ and R) and can be applied to a wide variety of experimental paradigms. We anticipate it will enable others to more easily take advantage of the powerful insights microglial morphology analysis provides.
    MeSH term(s) Animals ; CX3C Chemokine Receptor 1/physiology ; Diet, High-Fat ; Disease Models, Animal ; Green Fluorescent Proteins/metabolism ; Image Processing, Computer-Assisted/methods ; Inflammation/immunology ; Inflammation/metabolism ; Inflammation/pathology ; Mice ; Microglia/immunology ; Microglia/metabolism ; Microglia/pathology ; Microscopy, Fluorescence, Multiphoton/methods ; Software
    Chemical Substances CX3C Chemokine Receptor 1 ; Cx3cr1 protein, mouse ; Green Fluorescent Proteins (147336-22-9)
    Language English
    Publishing date 2021-08-11
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2630944-0
    ISSN 2046-2441 ; 2046-2441
    ISSN (online) 2046-2441
    ISSN 2046-2441
    DOI 10.1098/rsob.210045
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Debating intoxication: Response to commentaries.

    Crombag, Hans S / Child, John J / Sullivan, George R

    Addiction (Abingdon, England)

    2020  Volume 115, Issue 12, Page(s) 2210–2212

    MeSH term(s) Alcoholic Intoxication ; Alcoholism ; Criminal Law ; Dangerous Behavior ; Humans
    Language English
    Publishing date 2020-10-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 1141051-6
    ISSN 1360-0443 ; 0965-2140
    ISSN (online) 1360-0443
    ISSN 0965-2140
    DOI 10.1111/add.15257
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Drunk, dangerous and delusional: how legal concept-creep risks overcriminalization.

    Crombag, Hans S / Child, John J / Sullivan, G R

    Addiction (Abingdon, England)

    2020  Volume 115, Issue 12, Page(s) 2200–2207

    Abstract: Background: In the recent case of R v. Taj, the Court of Appeal of England and Wales upheld the conviction of a defendant who, in a psychotic delusional state, mistook his non-threatening victim to be a terrorist, violently attacking him. The law ... ...

    Abstract Background: In the recent case of R v. Taj, the Court of Appeal of England and Wales upheld the conviction of a defendant who, in a psychotic delusional state, mistook his non-threatening victim to be a terrorist, violently attacking him. The law typically allows honest mistakes (even if unreasonable) as a basis for self-defence (in this case the defence of others). However, because Taj's delusions were found by the court to have been caused by voluntary alcohol consumption, special legal (prior-fault) intoxication rules were applied to block his defence; Taj was convicted and sentenced to 19 years imprisonment for attempted murder.
    Argument: We focus here on the simple question-what does it mean to be intoxicated? On the facts, Taj did not have drugs active in his system at the time of the attack, but the court nonetheless insisted that Taj's delusional mistake was 'attributable to intoxication'; namely, to drink- and drug-taking in the previous days and weeks. This extended conception of intoxication was questionably distinguished from psychosis induced by withdrawal. Furthermore, the court was unreceptive to evidence of a long-standing, underlying mental health disorder. We argue that the court's expanded view of intoxication is problematic, in that intoxication-induced psychosis cannot be sharply distinguished from other causes such as mental disorders; and even if it could be distinguished, it should not give rise to blame and punishment in the same way as does conduct induced by chemically active intoxicants ('drug-on-board').
    Conclusion: The courts' expansion of the definition of intoxication is both legally and forensically problematic, introducing legal vagaries where the clinical science is already vague; and with intoxication frequently interlocking with historic intoxication and secondary or comorbid mental health conditions, the decision risks inappropriately and/or over-criminalizing defendants.
    MeSH term(s) Aggression ; Alcoholic Intoxication/psychology ; Criminal Law/legislation & jurisprudence ; Dangerous Behavior ; England ; Humans ; Male ; Psychotic Disorders/psychology
    Language English
    Publishing date 2020-03-21
    Publishing country England
    Document type Journal Article
    ZDB-ID 1141051-6
    ISSN 1360-0443 ; 0965-2140
    ISSN (online) 1360-0443
    ISSN 0965-2140
    DOI 10.1111/add.15024
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Visual cues associated with sweet taste increase short-term eating and grab attention in healthy volunteers.

    Yeomans, Martin R / Ridley-Siegert, Thomas / Vi, Chi / Crombag, Hans S

    Physiology & behavior

    2021  Volume 241, Page(s) 113600

    Abstract: Most studies that examine responses to food cues use images of actual foods as stimuli. Since foods are rewarding in multiple ways, it then becomes difficult to try and partial out the role of the importance of different aspects of food reward. Here we ... ...

    Abstract Most studies that examine responses to food cues use images of actual foods as stimuli. Since foods are rewarding in multiple ways, it then becomes difficult to try and partial out the role of the importance of different aspects of food reward. Here we aimed to evaluate the impact of novel visual cues specifically associated with the immediate sensory reward from a liked sweet taste. In the training phase, one visual cue (CSsweet) was associated with the experience of sweet taste (10%sucrose) and a second, control cue (CSneutral) with a neutral taste (artificial saliva) using a disguised training procedure. In Experiment 1, participants (n = 45) were given an ad libitum snack intake test 30 min post-training, either labelled with CSsweet or CSneutral. Total caloric consumption was significantly higher in the CSsweet (650 ± 47 kcal) than CSneutral (477 ± 45 kcal) condition, but ratings of liking for the snacks did not differ significantly between conditions. In Experiment 2, participants (n = 80) exhibited an overall attentional bias (22.1 ± 9.9 ms) for the CSsweet relative to CSneutral cue (assessed using a dot-probe task), however rated liking for the CSsweet did not change significantly after cue-sweet training. Likewise, measures of expected satiety for drinks labelled with CSsweet did not differ significantly from CSneutral. Overall these two experiments provide evidence that associations between neutral visual cues and the experience of a liked sweet taste leads to cue-potentiated eating in the presence of the CSsweet cue. With no evidence that cue-sweet training altered rated liking for the visual cues, and in keeping with extant literature on the dissociation of hedonic and rewarding properties of food rewards, we propose this potentiation effect to reflect increased incentive salience.
    MeSH term(s) Attention ; Cues ; Eating ; Food Preferences ; Healthy Volunteers ; Humans ; Snacks ; Taste
    Language English
    Publishing date 2021-09-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3907-x
    ISSN 1873-507X ; 0031-9384
    ISSN (online) 1873-507X
    ISSN 0031-9384
    DOI 10.1016/j.physbeh.2021.113600
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: An open-source pipeline for analysing changes in microglial morphology

    Devin Clarke / Hans S. Crombag / Catherine N. Hall

    Open Biology, Vol 11, Iss

    2021  Volume 8

    Abstract: Changes in microglial morphology are powerful indicators of the inflammatory state of the brain. Here, we provide an open-source microglia morphology analysis pipeline that first cleans and registers images of microglia, before extracting 62 parameters ... ...

    Abstract Changes in microglial morphology are powerful indicators of the inflammatory state of the brain. Here, we provide an open-source microglia morphology analysis pipeline that first cleans and registers images of microglia, before extracting 62 parameters describing microglial morphology. It then compares control and ‘inflammation’ training data and uses dimensionality reduction to generate a single metric of morphological change (an ‘inflammation index’). This index can then be calculated for test data to assess inflammation, as we demonstrate by investigating the effect of short-term high-fat diet consumption in heterozygous Cx3CR1-GFP mice, finding no significant effects of diet. Our pipeline represents the first open-source microglia morphology pipeline combining semi-automated image processing and dimensionality reduction. It uses free software (ImageJ and R) and can be applied to a wide variety of experimental paradigms. We anticipate it will enable others to more easily take advantage of the powerful insights microglial morphology analysis provides.
    Keywords microglia ; morphology ; in vivo ; two-photon ; image processing ; dimensionality reduction ; Biology (General) ; QH301-705.5
    Subject code 004
    Language English
    Publishing date 2021-08-01T00:00:00Z
    Publisher The Royal Society
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Acute, but not longer-term, exposure to environmental enrichment attenuates Pavlovian cue-evoked conditioned approach and Fos expression in the prefrontal cortex in mice.

    Margetts-Smith, Gabriella / Macnaghten, Anastasia I / Brebner, Leonie S / Ziminski, Joseph J / Sieburg, Meike C / Grimm, Jeffrey W / Crombag, Hans S / Koya, Eisuke

    The European journal of neuroscience

    2021  Volume 53, Issue 8, Page(s) 2580–2591

    Abstract: Exposure to environmental enrichment can modify the impact of motivationally relevant stimuli. For instance, previous studies in rats have found that even a brief, acute (~1 day), but not chronic, exposure to environmentally enriched (EE) housing ... ...

    Abstract Exposure to environmental enrichment can modify the impact of motivationally relevant stimuli. For instance, previous studies in rats have found that even a brief, acute (~1 day), but not chronic, exposure to environmentally enriched (EE) housing attenuates instrumental lever pressing for sucrose-associated cues in a conditioned reinforcement setup. Moreover, acute EE reduces corticoaccumbens activity, as measured by decreases in expression of the neuronal activity marker "Fos." Currently, it is not known whether acute EE also reduces sucrose seeking and corticoaccumbens activity elicited by non-contingent or "forced" exposure to sucrose cues, which more closely resembles cue exposure encountered in daily life. We therefore measured the effects of acute/intermittent (1 day or 6 day of EE prior to test day) versus chronic (EE throughout conditioning lasting until test day) EE on the ability of a Pavlovian sucrose cue to elicit sucrose seeking (conditioned approach) and Fos expression in the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), and nucleus accumbens (NAc) in mice. One day, but not 6 day or chronic EE , reduced sucrose seeking and Fos in the deep layers of the dorsal mPFC. By contrast, 1 day, 6 day, and chronic EE all reduced Fos in the shallow layers of the OFC. None of the EE manipulations modulated NAc Fos expression. We reveal how EE reduces behavioral reactivity to sucrose cues by reducing activity in select prefrontal cortical brain areas. Our work further demonstrates the robustness of EE in its ability to modulate various forms of reward-seeking across species.
    MeSH term(s) Animals ; Conditioning, Operant ; Cues ; Mice ; Nucleus Accumbens ; Prefrontal Cortex ; Rats ; Reinforcement, Psychology ; Reward
    Language English
    Publishing date 2021-03-02
    Publishing country France
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 645180-9
    ISSN 1460-9568 ; 0953-816X
    ISSN (online) 1460-9568
    ISSN 0953-816X
    DOI 10.1111/ejn.15146
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Visual cues associated with sweet taste increase short-term eating and grab attention in healthy volunteers

    Yeomans, Martin R. / Ridley-Siegert, Thomas / Vi, Chi / Crombag, Hans S.

    Physiology & behavior. 2021 Nov. 01, v. 241

    2021  

    Abstract: Most studies that examine responses to food cues use images of actual foods as stimuli. Since foods are rewarding in multiple ways, it then becomes difficult to try and partial out the role of the importance of different aspects of food reward. Here we ... ...

    Abstract Most studies that examine responses to food cues use images of actual foods as stimuli. Since foods are rewarding in multiple ways, it then becomes difficult to try and partial out the role of the importance of different aspects of food reward. Here we aimed to evaluate the impact of novel visual cues specifically associated with the immediate sensory reward from a liked sweet taste. In the training phase, one visual cue (CSsweet) was associated with the experience of sweet taste (10%sucrose) and a second, control cue (CSneutral) with a neutral taste (artificial saliva) using a disguised training procedure. In Experiment 1, participants (n = 45) were given an ad libitum snack intake test 30 min post-training, either labelled with CSsweet or CSneutral. Total caloric consumption was significantly higher in the CSsweet (650 ± 47 kcal) than CSneutral (477 ± 45 kcal) condition, but ratings of liking for the snacks did not differ significantly between conditions. In Experiment 2, participants (n = 80) exhibited an overall attentional bias (22.1 ± 9.9 ms) for the CSsweet relative to CSneutral cue (assessed using a dot-probe task), however rated liking for the CSsweet did not change significantly after cue-sweet training. Likewise, measures of expected satiety for drinks labelled with CSsweet did not differ significantly from CSneutral. Overall these two experiments provide evidence that associations between neutral visual cues and the experience of a liked sweet taste leads to cue-potentiated eating in the presence of the CSsweet cue. With no evidence that cue-sweet training altered rated liking for the visual cues, and in keeping with extant literature on the dissociation of hedonic and rewarding properties of food rewards, we propose this potentiation effect to reflect increased incentive salience.
    Keywords behavior ; dissociation ; energy intake ; food intake ; saliva ; satiety ; sweetness ; taste
    Language English
    Dates of publication 2021-1101
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 3907-x
    ISSN 1873-507X ; 0031-9384
    ISSN (online) 1873-507X
    ISSN 0031-9384
    DOI 10.1016/j.physbeh.2021.113600
    Database NAL-Catalogue (AGRICOLA)

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  8. Article ; Online: Reward Devaluation Attenuates Cue-Evoked Sucrose Seeking and Is Associated with the Elimination of Excitability Differences between Ensemble and Non-ensemble Neurons in the Nucleus Accumbens.

    Sieburg, Meike C / Ziminski, Joseph J / Margetts-Smith, Gabriella / Reeve, Hayley M / Brebner, Leonie S / Crombag, Hans S / Koya, Eisuke

    eNeuro

    2019  Volume 6, Issue 6

    Abstract: Animals must learn relationships between foods and the environmental cues that predict their availability for survival. Such cue-food associations are encoded in sparse sets of neurons or "neuronal ensembles" in the nucleus accumbens (NAc). For these ... ...

    Abstract Animals must learn relationships between foods and the environmental cues that predict their availability for survival. Such cue-food associations are encoded in sparse sets of neurons or "neuronal ensembles" in the nucleus accumbens (NAc). For these ensemble-encoded, cue-controlled appetitive responses to remain adaptive, they must allow for their dynamic updating depending on acute changes in internal states such as physiological hunger or the perceived desirability of food. However, how these neuronal ensembles are recruited and physiologically modified following the update of such learned associations is unclear. To investigate this, we examined the effects of devaluation on ensemble plasticity at the levels of recruitment, intrinsic excitability, and synaptic physiology in sucrose-conditioned
    MeSH term(s) Animals ; Conditioning, Operant/drug effects ; Conditioning, Operant/physiology ; Cues ; Drug-Seeking Behavior/drug effects ; Drug-Seeking Behavior/physiology ; Male ; Mice ; Mice, Transgenic ; Neuronal Plasticity/drug effects ; Neuronal Plasticity/physiology ; Neurons/drug effects ; Neurons/physiology ; Nucleus Accumbens/drug effects ; Nucleus Accumbens/physiology ; Proto-Oncogene Proteins c-fos/metabolism ; Reward ; Sucrose/administration & dosage
    Chemical Substances Proto-Oncogene Proteins c-fos ; Sucrose (57-50-1)
    Language English
    Publishing date 2019-12-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2800598-3
    ISSN 2373-2822 ; 2373-2822
    ISSN (online) 2373-2822
    ISSN 2373-2822
    DOI 10.1523/ENEURO.0338-19.2019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Regional Differences in Striatal Neuronal Ensemble Excitability Following Cocaine and Extinction Memory Retrieval in Fos-GFP Mice.

    Ziminski, Joseph J / Sieburg, Meike C / Margetts-Smith, Gabriella / Crombag, Hans S / Koya, Eisuke

    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

    2017  Volume 43, Issue 4, Page(s) 718–727

    Abstract: Learned associations between drugs of abuse and the drug administration environment have an important role in addiction. In rodents, exposure to a drug-associated environment elicits conditioned psychomotor activation, which may be weakened following ... ...

    Abstract Learned associations between drugs of abuse and the drug administration environment have an important role in addiction. In rodents, exposure to a drug-associated environment elicits conditioned psychomotor activation, which may be weakened following extinction (EXT) learning. Although widespread drug-induced changes in neuronal excitability have been observed, little is known about specific changes within neuronal ensembles activated during the recall of drug-environment associations. Using a cocaine-conditioned locomotion (CL) procedure, the present study assessed the excitability of neuronal ensembles in the nucleus accumbens core and shell (NAc
    MeSH term(s) Animals ; Cocaine/pharmacology ; Corpus Striatum/drug effects ; Corpus Striatum/physiology ; Dopamine Uptake Inhibitors/pharmacology ; Extinction, Psychological/drug effects ; Extinction, Psychological/physiology ; Green Fluorescent Proteins/biosynthesis ; Locomotion/drug effects ; Locomotion/physiology ; Male ; Memory/drug effects ; Memory/physiology ; Mice ; Mice, Inbred C57BL ; Neurons/drug effects ; Neurons/physiology ; Proto-Oncogene Proteins c-fos/biosynthesis
    Chemical Substances Dopamine Uptake Inhibitors ; Proto-Oncogene Proteins c-fos ; Green Fluorescent Proteins (147336-22-9) ; Cocaine (I5Y540LHVR)
    Language English
    Publishing date 2017-05-25
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639471-1
    ISSN 1740-634X ; 0893-133X
    ISSN (online) 1740-634X
    ISSN 0893-133X
    DOI 10.1038/npp.2017.101
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Whether or not to eat: A controlled laboratory study of discriminative cueing effects on food intake in humans.

    Ridley-Siegert, Thomas L / Crombag, Hans S / Yeomans, Martin R

    Physiology & behavior

    2015  Volume 152, Issue Pt B, Page(s) 347–353

    Abstract: There is a wealth of data showing a large impact of food cues on human ingestion, yet most studies use pictures of food where the precise nature of the associations between the cue and food is unclear. To test whether novel cues which were associated ... ...

    Abstract There is a wealth of data showing a large impact of food cues on human ingestion, yet most studies use pictures of food where the precise nature of the associations between the cue and food is unclear. To test whether novel cues which were associated with the opportunity of winning access to food images could also impact ingestion, 63 participants participated in a game in which novel visual cues signalled whether responding on a keyboard would win (a picture of) chocolate, crisps, or nothing. Thirty minutes later, participants were given an ad libitum snack-intake test during which the chocolate-paired cue, the crisp-paired cue, the non-winning cue and no cue were presented as labels on the food containers. The presence of these cues significantly altered overall intake of the snack foods; participants presented with food labelled with the cue that had been associated with winning chocolate ate significantly more than participants who had been given the same products labelled with the cue associated with winning nothing, and in the presence of the cue signalling the absence of food reward participants tended to eat less than all other conditions. Surprisingly, cue-dependent changes in food consumption were unaffected by participants' level of contingency awareness. These results suggest that visual cues that have been pre-associated with winning, but not consuming, a liked food reward modify food intake consistent with current ideas that the abundance of food associated cues may be one factor underlying the 'obesogenic environment'.
    MeSH term(s) Adolescent ; Adult ; Cacao ; Conditioning, Operant ; Craving ; Cues ; Eating/psychology ; Feeding Behavior/psychology ; Female ; Games, Experimental ; Humans ; Male ; Middle Aged ; Photic Stimulation ; Psychological Tests ; Reward ; Snacks/psychology ; Solanum tuberosum ; Taste Perception ; Visual Perception ; Young Adult
    Language English
    Publishing date 2015-12-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3907-x
    ISSN 1873-507X ; 0031-9384
    ISSN (online) 1873-507X
    ISSN 0031-9384
    DOI 10.1016/j.physbeh.2015.06.039
    Database MEDical Literature Analysis and Retrieval System OnLINE

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