Imperial College London

DrMatthewWall

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Honorary Senior Lecturer
 
 
 
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Contact

 

matthew.wall

 
 
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Location

 

Burlington DanesHammersmith Campus

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Summary

 

Publications

Publication Type
Year
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59 results found

Mokrysz C, Shaban NDC, Freeman TP, Lawn W, Pope RA, Hindocha C, Freeman A, Wall MB, Bloomfield MAP, Morgan CJA, Nutt DJ, Curran HVet al., 2021, Acute effects of cannabis on speech illusions and psychotic-like symptoms: two studies testing the moderating effects of cannabidiol and adolescence, PSYCHOLOGICAL MEDICINE, Vol: 51, Pages: 2134-2142, ISSN: 0033-2917

Journal article

Comninos A, Yang L, OCallaghan J, Mills E, Wall M, Demetriou L, Wing V, Thurston L, Owen B, Abbara A, Rabiner E, Dhillo Wet al., 2021, Kisspeptin modulates gamma-aminobutyric acid levels in the human brain, Psychoneuroendocrinology, Vol: 129, Pages: 1-5, ISSN: 0306-4530

Gamma-aminobutyric acid (GABA) is a key inhibitory neurotransmitter that has been implicated in the aetiology of common mood and behavioural disorders. By employing proton magnetic resonance spectroscopy in man, we demonstrate that administration of the reproductive neuropeptide, kisspeptin, robustly decreases GABA levels in the limbic system of the human brain; specifically the anterior cingulate cortex (ACC). This finding defines a novel kisspeptin-activated GABA pathway in man, and provides important mechanistic insights into the mood and behaviour-altering effects of kisspeptin seen in rodents and humans. In addition, this work has therapeutic implications as it identifies GABA-signalling as a potential target for the escalating development of kisspeptin-based therapies for common reproductive disorders of body and mind.

Journal article

Salem V, Demetriou L, Behary P, Alexiadou K, Scholtz S, Tharakan G, Miras A, Purkayastha S, Ahmed A, Bloom S, Wall M, Dhillo W, Tan Tet al., 2021, Weight loss by low calorie diet versus gastric bypass surgery in people with diabetes results in divergent brain activation patterns: an functional MRI study, Diabetes Care, Vol: 44, Pages: 1842-1851, ISSN: 0149-5992

OBJECTIVE: Weight loss achieved with very-low-calorie diets (VLCDs) can produce remission of type 2 diabetes (T2D), but weight regain very often occurs with reintroduction of higher calorie intakes. In contrast, bariatric surgery produces clinically significant and durable weight loss, with diabetes remission that translates into reductions in mortality. We hypothesized that in patients living with obesity and prediabetes/T2D, longitudinal changes in brain activity in response to food cues as measured using functional MRI would explain this difference.RESEARCH DESIGN AND METHODS: Sixteen participants underwent gastric bypass surgery, and 19 matched participants undertook a VLCD (meal replacement) for 4 weeks. Brain responses to food cues and resting-state functional connectivity were assessed with functional MRI pre- and postintervention and compared across groups.RESULTS: We show that Roux-en-Y gastric bypass surgery (RYGB) results in three divergent brain responses compared with VLCD-induced weight loss: 1) VLCD resulted in increased brain reward center food cue responsiveness, whereas in RYGB, this was reduced; 2) VLCD resulted in higher neural activation of cognitive control regions in response to food cues associated with exercising increased cognitive restraint over eating, whereas RYGB did not; and 3) a homeostatic appetitive system (centered on the hypothalamus) is better engaged following RYGB-induced weight loss than VLCD.CONCLUSIONS: Taken together, these findings point to divergent brain responses to different methods of weight loss in patients with diabetes, which may explain weight regain after a short-term VLCD in contrast to enduring weight loss after RYGB.

Journal article

Hannaway N, Lao-Kaim NP, Martin-Bastida A, Roussakis A-A, Howard J, Wall MB, Loane C, Barker RA, Piccini Pet al., 2021, Longitudinal changes in movement-related functional MRI activity in Parkinson's disease patients, PARKINSONISM & RELATED DISORDERS, Vol: 87, Pages: 61-69, ISSN: 1353-8020

Journal article

Yang L, Demetriou L, Wall MB, Mills EG, Wing VC, Thurston L, Schaufelberger CN, Owen BM, Abbara A, Rabiner EA, Comninos AN, Dhillo WSet al., 2021, The Effects of Kisspeptin on Brain Response to Food Images and Psychometric Parameters of Appetite in Healthy Men, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 106, Pages: E1837-E1848, ISSN: 0021-972X

Journal article

Lawn W, Hill J, Hindocha C, Yim J, Yamamori Y, Jones G, Walker H, Green SF, Wall MB, Howes OD, Curran HV, Freeman TP, Bloomfield MAPet al., 2020, The acute effects of cannabidiol on the neural correlates of reward anticipation and feedback in healthy volunteers, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 34, Pages: 969-980, ISSN: 0269-8811

Journal article

Borissova A, Ferguson B, Wall MB, Morgan CJA, Carhart-Harris RL, Bolstridge M, Bloomfield MAP, Williams TM, Feilding A, Murphy K, Tyacke RJ, Erritzoe D, Stewart L, Wolff K, Nutt D, Curran HV, Lawn Wet al., 2020, Acute effects of MDMA on trust, cooperative behaviour and empathy: A double-blind, placebo-controlled experiment, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 35, Pages: 547-555, ISSN: 0269-8811

Journal article

Botvinik-Nezer R, Holzmeister F, Camerer CF, Dreber A, Huber J, Johannesson M, Kirchler M, Iwanir R, Mumford JA, Adcock RA, Avesani P, Baczkowski BM, Bajracharya A, Bakst L, Ball S, Barilari M, Bault N, Beaton D, Beitner J, Benoit RG, Berkers RMWJ, Bhanji JP, Biswal BB, Bobadilla-Suarez S, Bortolini T, Bottenhorn KL, Bowring A, Braem S, Brooks HR, Brudner EG, Calderon CB, Camilleri JA, Castrellon JJ, Cecchetti L, Cieslik EC, Cole ZJ, Collignon O, Cox RW, Cunningham WA, Czoschke S, Dadi K, Davis CP, Luca AD, Delgado MR, Demetriou L, Dennison JB, Di X, Dickie EW, Dobryakova E, Donnat CL, Dukart J, Duncan NW, Durnez J, Eed A, Eickhoff SB, Erhart A, Fontanesi L, Fricke GM, Fu S, Galvan A, Gau R, Genon S, Glatard T, Glerean E, Goeman JJ, Golowin SAE, Gonzalez-Garcia C, Gorgolewski KJ, Grady CL, Green MA, Guassi Moreira JF, Guest O, Hakimi S, Hamilton JP, Hancock R, Handjaras G, Harry BB, Hawco C, Herholz P, Herman G, Heunis S, Hoffstaedter F, Hogeveen J, Holmes S, Hu C-P, Huettel SA, Hughes ME, Iacovella V, Iordan AD, Isager PM, Isik AI, Jahn A, Johnson MR, Johnstone T, Joseph MJE, Juliano AC, Kable JW, Kassinopoulos M, Koba C, Kong X-Z, Koscik TR, Kucukboyaci NE, Kuhl BA, Kupek S, Laird AR, Lamm C, Langner R, Lauharatanahirun N, Lee H, Lee S, Leemans A, Leo A, Lesage E, Li F, Li MYC, Lim PC, Lintz EN, Liphardt SW, Losecaat Vermeer AB, Love BC, Mack ML, Malpica N, Marins T, Maumet C, McDonald K, McGuire JT, Melero H, Mendez Leal AS, Meyer B, Meyer KN, Mihai G, Mitsis GD, Moll J, Nielson DM, Nilsonne G, Notter MP, Olivetti E, Onicas AI, Papale P, Patil KR, Peelle JE, Perez A, Pischedda D, Poline J-B, Prystauka Y, Ray S, Reuter-Lorenz PA, Reynolds RC, Ricciardi E, Rieck JR, Rodriguez-Thompson AM, Romyn A, Salo T, Samanez-Larkin GR, Sanz-Morales E, Schlichting ML, Schultz DH, Shen Q, Sheridan MA, Silvers JA, Skagerlund K, Smith A, Smith DV, Sokol-Hessner P, Steinkamp SR, Tashjian SM, Thirion B, Thorp JN, Tinghog G, Tisdall L, Tompson SH, Toro-Serey C, Torre Tresols JJ, Tozzet al., 2020, Variability in the analysis of a single neuroimaging dataset by many teams, NATURE, Vol: 582, Pages: 84-+, ISSN: 0028-0836

Journal article

Yang L, Demetriou L, Wall M, Mills E, Zargaran D, Sykes M, Prague J, Abbara A, Owen B, Bassett P, Rabiner E, Comninos A, Dhillo Wet al., 2020, Kisspeptin enhances brain responses to olfactory and visual cues of attraction in men, JCI insight, Vol: 5, ISSN: 2379-3708

Successful reproduction is a fundamental physiological process which relies on the integration of sensory cues of attraction with appropriate emotions and behaviors and the reproductive axis. However, the factors responsible for this integration remain largely unexplored. Using functional neuroimaging, hormonal and psychometric analyses, we demonstrate that the reproductive hormone kisspeptin enhances brain activity in response to olfactory and visual cues of attraction in men. Furthermore, the brain regions enhanced by kisspeptin correspond to areas within the olfactory and limbic systems that govern sexual behavior and perception of beauty as well as overlapping with its endogenous expression pattern. Of key functional and behavioral significance, we observed that kisspeptin was most effective in men with lower sexual quality of life scores. As such, our results reveal a previously undescribed attraction pathway in humans activated by kisspeptin, and identify kisspeptin signaling as a new therapeutic target for related reproductive and psychosexual disorders.

Journal article

Mertens LJ, Wall MB, Roseman L, Demetriou L, Nutt DJ, Carhart-Harris RLet al., 2020, Therapeutic mechanisms of psilocybin: Changes in amygdala and prefrontal functional connectivity during emotional processing after psilocybin for treatment-resistant depression, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 34, Pages: 167-180, ISSN: 0269-8811

Journal article

Mertens LJ, Wall MB, Roseman L, Demetriou L, Nutt DJ, Carhart-Harris RLet al., 2019, Therapeutic mechanisms of psychedelic drugs: Changes in amygdala and prefrontal functional connectivity during emotional processing after psilocybin for treatment-resistant depression, 32nd Congress of the European-College-of-Neuropsychopharmacology (ECNP), Publisher: ELSEVIER, Pages: S416-S417, ISSN: 0924-977X

Conference paper

Nour MM, Dahoun T, McCutcheon RA, Adams RA, Wall MB, Howes ODet al., 2019, Task-induced functional brain connectivity mediates the relationship between striatal D2/3 receptors and working memory, eLife, Vol: 8, Pages: 1-23, ISSN: 2050-084X

Working memory performance is thought to depend on both striatal dopamine 2/3 receptors (D2/3Rs) and task-induced functional organisation in key cortical brain networks. Here, we combine functional magnetic resonance imaging and D2/3R positron emission tomography in 51 healthy volunteers, to investigate the relationship between working memory performance, task-induced default mode network (DMN) functional connectivity changes, and striatal D2/3R availability. Increasing working memory load was associated with reduced DMN functional connectivity, which was itself associated with poorer task performance. Crucially, the magnitude of the DMN connectivity reduction correlated with striatal D2/3R availability, particularly in the caudate, and this relationship mediated the relationship between striatal D2/3R availability and task performance. These results inform our understanding of natural variation in working memory performance, and have implications for understanding age-related cognitive decline and cognitive impairments in neuropsychiatric disorders where dopamine signalling is altered.

Journal article

Hannaway N, Lao-Kaim NP, Martin-Bastida A, Roussakis A-A, Howard J, Wall MB, Loane C, Barker RA, Piccini Pet al., 2019, Functional responses to joystick movements during Parkinson's disease progression: a longitudinal fMRI study, 5th Congress of the European-Academy-of-Neurology (EAN), Publisher: WILEY, Pages: 227-227, ISSN: 1351-5101

Conference paper

Wall MB, Pope R, Freeman TP, Kowalczyk OS, Demetriou L, Mokrysz C, Hindocha C, Lawn W, Bloomfield MAP, Freeman AM, Feilding A, Nutt D, Curran HVet al., 2019, Dissociable effects of cannabis with and without cannabidiol on the human brain's resting-state functional connectivity, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 33, Pages: 822-830, ISSN: 0269-8811

Journal article

Wall MB, 2019, Reliability starts with the experimental tools employed, CORTEX, Vol: 113, Pages: 352-354, ISSN: 0010-9452

Journal article

Bloomfield MAP, Hindocha C, Green SF, Wall MB, Lees R, Petrilli K, Costello H, Ogunbiyi MO, Bossong MG, Freeman TPet al., 2019, The neuropsychopharmacology of cannabis: A review of human imaging studies, Pharmacology and Therapeutics, Vol: 195, Pages: 132-161, ISSN: 0163-7258

The laws governing cannabis are evolving worldwide and associated with changing patterns of use. The main psychoactive drug in cannabis is Δ9-tetrahydrocannabinol (THC), a partial agonist at the endocannabinoid CB1 receptor. Acutely, cannabis and THC produce a range of effects on several neurocognitive and pharmacological systems. These include effects on executive, emotional, reward and memory processing via direct interactions with the endocannabinoid system and indirect effects on the glutamatergic, GABAergic and dopaminergic systems. Cannabidiol, a non-intoxicating cannabinoid found in some forms of cannabis, may offset some of these acute effects. Heavy repeated cannabis use, particularly during adolescence, has been associated with adverse effects on these systems, which increase the risk of mental illnesses including addiction and psychosis. Here, we provide a comprehensive state of the art review on the acute and chronic neuropsychopharmacology of cannabis by synthesizing the available neuroimaging research in humans. We describe the effects of drug exposure during development, implications for understanding psychosis and cannabis use disorder, and methodological considerations. Greater understanding of the precise mechanisms underlying the effects of cannabis may also give rise to new treatment targets.

Journal article

Roseman L, Demetriou L, Wall M, Nutt D, Carhart-Harris RLet al., 2018, Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression, Neuropharmacology, Vol: 142, Pages: 263-269, ISSN: 0028-3908

Recent evidence indicates that psilocybin with psychological support may be effective for treating depression. Some studies have found that patients with depression show heightened amygdala responses to fearful faces and there is reliable evidence that treatment with SSRIs attenuates amygdala responses (Ma, 2015). We hypothesised that amygdala responses to emotional faces would be altered post-treatment with psilocybin. In this open-label study, 20 individuals diagnosed with moderate to severe, treatment-resistant depression, underwent two separate dosing sessions with psilocybin. Psychological support was provided before, during and after these sessions and 19 completed fMRI scans one week prior to the first session and one day after the second and last. Neutral, fearful and happy faces were presented in the scanner and analyses focused on the amygdala. Group results revealed rapid and enduring improvements in depressive symptoms post psilocybin. Increased responses to fearful and happy faces were observed in the right amygdala post-treatment, and right amygdala increases to fearful versus neutral faces were predictive of clinical improvements at 1-week. Psilocybin with psychological support was associated with increased amygdala responses to emotional stimuli, an opposite effect to previous findings with SSRIs. This suggests fundamental differences in these treatments’ therapeutic actions, with SSRIs mitigating negative emotions and psilocybin allowing patients to confront and work through them. Based on the present results, we propose that psilocybin with psychological support is a treatment approach that potentially revives emotional responsiveness in depression, enabling patients to reconnect with their emotions.

Journal article

Nour MM, Dahoun T, Schwartenbeck P, Adams RA, FitzGerald THB, Coello C, Wall MB, Dolan RJ, Howes ODet al., 2018, Dopaminergic basis for signaling belief updates, but not surprise, and the link to paranoia, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 115, Pages: E10167-E10176, ISSN: 0027-8424

Journal article

Comninos A, Demetriou L, Wall M, Shah A, Clarke S, Narayanaswamy S, Nesbitt A, Izzi-Engbeaya C, Prague J, Abbara A, Ratnasabapathy R, Yang LY, Salem V, Nijher G, Jayasena C, Tanner M, Bassett P, Mehta A, McGonigle J, Rabiner E, Bloom S, Dhillo Wet al., 2018, Modulations of human resting brain connectivity by Kisspeptin enhance sexual and emotional Functions, JCI insight, Vol: 3, Pages: 1-11, ISSN: 2379-3708

BACKGROUND. Resting brain connectivity is a crucial component of human behavior demonstrated by disruptions in psychosexual and emotional disorders. Kisspeptin, a recently identified critical reproductive hormone, can alter activity in certain brain structures but its effects on resting brain connectivity and networks in humans remain elusive.METHODS. We determined the effects of kisspeptin on resting brain connectivity (using functional neuroimaging) and behavior (using psychometric analyses) in healthy men, in a randomized double-blinded 2-way placebo-controlled study.RESULTS. Kisspeptin’s modulation of the default mode network (DMN) correlated with increased limbic activity in response to sexual stimuli (globus pallidus r = 0.500, P = 0.005; cingulate r = 0.475, P = 0.009). Furthermore, kisspeptin’s DMN modulation was greater in men with less reward drive (r = –0.489, P = 0.008) and predicted reduced sexual aversion (r = –0.499, P = 0.006), providing key functional significance. Kisspeptin also enhanced key mood connections including between the amygdala-cingulate, hippocampus-cingulate, and hippocampus–globus pallidus (all P < 0.05). Consistent with this, kisspeptin’s enhancement of hippocampus–globus pallidus connectivity predicted increased responses to negative stimuli in limbic structures (including the thalamus and cingulate [all P < 0.01]).CONCLUSION. Taken together, our data demonstrate a previously unknown role for kisspeptin in the modulation of functional brain connectivity and networks, integrating these with reproductive hormones and behaviors. Our findings that kisspeptin modulates resting brain connectivity to enhance sexual and emotional processing and decrease sexual aversion, provide foundation for kisspeptin-based therapies for associated disorders of body and mind.

Journal article

Harvey J-L, Demetriou L, McGonigle J, Wall MBet al., 2018, A short, robust brain activation control task optimised for pharmacological fMRI studies, PeerJ, Vol: 6, ISSN: 2167-8359

BackgroundFunctional magnetic resonance imaging (fMRI) is a popular method for examining pharmacological effects on the brain; however, the BOLD response is dependent on intact neurovascular coupling, and potentially modulated by a number of physiological factors. Pharmacological fMRI is therefore vulnerable to confounding effects of pharmacological probes on general physiology or neurovascular coupling. Controlling for such non-specific effects in pharmacological fMRI studies is therefore an important consideration, and there is an additional need for well-validated fMRI task paradigms that could be used to control for such effects, or for general testing purposes.MethodsWe have developed two variants of a standardized control task that are short (5 minutes duration) simple (for both the subject and experimenter), widely applicable, and yield a number of readouts in a spatially diverse set of brain networks. The tasks consist of four functionally discrete three-second trial types (plus additional null trials) and contain visual, auditory, motor and cognitive (eye-movements, and working memory tasks in the two task variants) stimuli. Performance of the tasks was assessed in a group of 15 subjects scanned on two separate occasions, with test-retest reliability explicitly assessed using intra-class correlation coefficients.ResultsBoth tasks produced robust patterns of brain activation in the expected brain regions, and region of interest-derived reliability coefficients for the tasks were generally high, with four out of eight task conditions rated as ‘excellent’ or ‘good’, and only one out of eight rated as ‘poor’. Median values in the voxel-wise reliability measures were also >0.7 for all task conditions, and therefore classed as ‘excellent’ or ‘good’. The spatial concordance between the most highly activated voxels and those with the highest reliability coefficients was greater for the sensory (auditory

Journal article

Demetriou L, Kowalczyk OS, Tyson G, Bello T, Newbould RD, Wall MBet al., 2018, A comprehensive evaluation of increasing temporal resolution with multiband-accelerated protocols and effects on statistical outcome measures in fMRI, NEUROIMAGE, Vol: 176, Pages: 404-416, ISSN: 1053-8119

Journal article

Nour M, Dahoun T, Schwartenbeck P, Adams R, FitzGerald T, Coello C, Wall M, Dolan R, Howes Oet al., 2018, THE ROLE OF DOPAMINE IN PROCESSING THE MEANINGFUL INFORMATION OF OBSERVATIONS, AND IMPLICATIONS FOR THE ABERRANT SALIENCE HYPOTHESIS OF SCHIZOPHRENIA, 6th Biennial Conference of the Schizophrenia-International-Research-Society (SIRS), Publisher: OXFORD UNIV PRESS, Pages: S385-S385, ISSN: 0586-7614

Conference paper

Carhart-Harris RL, Roseman L, Bolstridge M, Demetriou L, Pannekoek JN, Wall MB, Tanner M, Kaelen M, McGonigle J, Murphy K, Leech R, Curran HV, Nutt DJet al., 2017, Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms, Scientific Reports, Vol: 7, ISSN: 2045-2322

Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. Here, cerebral blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) were measured with functional magnetic resonance imaging (fMRI) before and after treatment with psilocybin (serotonin agonist) for treatment-resistant depression (TRD). Quality pre and post treatment fMRI data were collected from 16 of 19 patients. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. Whole-brain analyses revealed post-treatment decreases in CBF in the temporal cortex, including the amygdala. Decreased amygdala CBF correlated with reduced depressive symptoms. Focusing on a priori selected circuitry for RSFC analyses, increased RSFC was observed within the default-mode network (DMN) post-treatment. Increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex RSFC was predictive of treatment response at 5-weeks, as was decreased parahippocampal-prefrontal cortex RSFC. These data fill an important knowledge gap regarding the post-treatment brain effects of psilocybin, and are the first in depressed patients. The post-treatment brain changes are different to previously observed acute effects of psilocybin and other ‘psychedelics’ yet were related to clinical outcomes. A ‘reset’ therapeutic mechanism is proposed.

Journal article

Wall MB, Mentink A, Lyons G, Kowalczyk OS, Demetriou L, Newbould RDet al., 2017, Investigating the neural correlates of smoking: feasibility and results of combining electronic cigarettes with fMRI, Scientific Reports, Vol: 7, ISSN: 2045-2322

Cigarette addiction is driven partly by the physiological effects of nicotine, but also by the distinctive sensory and behavioural aspects of smoking, and understanding the neural effects of such processes is vital. There are many practical difficulties associated with subjects smoking in the modern neuroscientific laboratory environment, however electronic cigarettes obviate many of these issues, and provide a close simulation of smoking tobacco cigarettes. We have examined the neural effects of ‘smoking’ electronic cigarettes with concurrent functional Magnetic Resonance Imaging (fMRI). The results demonstrate the feasibility of using these devices in the MRI environment, and show brain activation in a network of cortical (motor cortex, insula, cingulate, amygdala) and sub-cortical (putamen, thalamus, globus pallidus, cerebellum) regions. Concomitant relative deactivations were seen in the ventral striatum and orbitofrontal cortex. These results reveal the brain processes involved in (simulated) smoking for the first time, and validate a novel approach to the study of smoking, and addiction more generally.

Journal article

Freeman TP, Pope RA, Wall MB, Bisby JA, Luijten M, Hindocha C, Mokrysz C, Lawn W, Moss A, Bloomfield MAP, Morgan CJA, Nutt DJ, Curran HVet al., 2017, Cannabis dampens the effects of music in brain regions sensitive to reward and emotion, International Journal of Neuropsychopharmacology, Vol: 21, Pages: 21-32, ISSN: 1461-1457

Background: Despite the current shift towards permissive cannabis policies, few studies have investigated the pleasurable effects users seek. Here we investigate the effects of cannabis on listening to music - a rewarding activity that frequently occurs in the context of recreational cannabis use. We additionally tested how these effects are influenced by cannabidiol (CBD), which may offset cannabis-related harms. Methods: Across three sessions, sixteen cannabis users inhaled cannabis with CBD, cannabis without CBD, and placebo. We compared their response to music relative to control excerpts of scrambled sound during functional Magnetic Resonance Imaging (fMRI) within regions identified in a meta-analysis of music-evoked reward and emotion. All results were False Discovery Rate corrected (p<0.05). Results: Compared to placebo, cannabis without CBD dampened response to music in bilateral auditory cortex (right: p=0.005, left: p=0.008), right hippocampus/parahippocampal gyrus (p=0.025), right amygdala (p=0.025) and right ventral striatum (p=0.033). Across all sessions, the effects of music in this ventral striatal region correlated with pleasure ratings (p=0.002) and increased functional connectivity with auditory cortex (right: p=0.000, left: p=0.000), supporting its involvement in music reward. Functional connectivity between right ventral striatum and auditory cortex was increased by CBD (right: p=0.003, left: p=0.030), and cannabis with CBD did not differ from placebo on any fMRI measures. Both types of cannabis increased ratings of wanting to listen to music (p<0.002) and enhanced sound perception (p<0.001). Conclusions: Cannabis dampens the effects of music in brain regions sensitive to reward and emotion. These effects were offset by a key cannabis constituent, cannabidol.

Journal article

Comninos A, Wall M, Demetriou L, Shah AJ, Clarke S, Narayanaswamy S, Nesbitt A, Izzi-engbeaya C, Prague J, Abbara A, Ratnasabapathy R, Salem V, Nijher G, Jayasena C, Tanner M, Bassett P, Mehta A, Rabiner E, Honigsperger C, Silva MR, Brandtzaeg OK, Lundanes E, Wilson SR, Brown RC, Thomas SA, Bloom SR, Dhillo WSet al., 2017, Kisspeptin modulates sexual and emotional brain processing in humans, Journal of Clinical Investigation, Vol: 127, Pages: 709-719, ISSN: 1558-8238

Background. Sex, emotion, and reproduction are fundamental and tightly entwined aspects of human behaviour. At a population level in humans, both the desire for sexual stimulation and the desire to bond with a partner are important precursors to reproduction. However, the relationships between these processes are incompletely understood. The limbic brain system has key roles in sexual and emotional behaviours, and is a likely candidate system for the integration of behaviour with the hormonal reproductive axis. We investigated the effects of kisspeptin, a recently identified key reproductive hormone, on limbic brain activity and behaviour.Methods. Using a combination of hormonal, functional neuroimaging and psychometric analyses we compared the effects of kisspeptin versus vehicle administration in 29 healthy heterosexual young men.Results. We demonstrate that kisspeptin enhances limbic brain activity specifically in response to sexual and couple-bonding stimuli. Furthermore, kisspeptin’s enhancement of limbic brain structures correlated with psychometric measures of reward, drive, mood and sexual aversion providing functional significance. In addition, kisspeptin administration attenuated negative mood.Conclusion. Collectively, our data provide evidence of a novel role for kisspeptin in the integration of sexual and emotional brain processing with reproduction in humans, and have important implications for our understanding of reproductive biology highly relevant to the current pharmacological development of kisspeptin as a potential therapeutic agent for patients with common disorders of reproductive function.

Journal article

Quelch D, Mick I, McGonigle J, Ramos A, Flechais R, Bolstridge M, Rabiner E, Wall MB, Newbould R, Steiniger-Brach B, van den Berg F, Boyce M, Ƙstergaard Nilausen D, Breuning Sluth L, Meulien D, von der Goltz C, Nutt D, Lingford-Hughes ARet al., 2017, Nalmefene reduces reward anticipation in alcohol dependence: an experimental functional magnetic resonance imaging study, Biological Psychiatry, Vol: 81, Pages: 941-948, ISSN: 1873-2402

BackgroundNalmefene (Selincro®) is a µ- and δ- opioid receptor antagonist, κ-opioid receptor partial agonist that has recently been approved in Europe for treating alcohol dependence. It offers a treatment approach for alcohol dependent individuals with “high risk drinking levels” to reduce their alcohol consumption. However, the neurobiological mechanism underpinning its effects on alcohol consumption remains to be determined. Using a randomised, double blind, placebo controlled within subject cross-over design we aimed to determine the effect of a single dose of nalmefene on striatal BOLD (blood oxygen level dependent) signal change during anticipation of monetary reward using the Monetary Incentive Delay Task following alcohol challenge.Methods and Materials22 currently heavy drinking, non-treatment seeking alcohol dependent males were recruited. The effect of single dose nalmefene (18mg; Selincro®) on changes in a priori defined striatal region of interest (ROI) BOLD signal change during reward anticipation compared with placebo were investigated using functional MRI (magnetic resonance imaging). Both conditions were performed under intravenous alcohol administration (6% v/v infusion to achieve a target level of 80mg%).ResultsDatasets from 18 participants were available and showed that in the presence of the alcohol infusion, nalmefene significantly reduced the BOLD response in the striatal ROI compared with placebo. Nalmefene did not alter brain perfusion.DiscussionNalmefene blunts BOLD response in the mesolimbic system during anticipation of monetary reward and an alcohol infusion. This is consistent with nalmefene’s actions on opiate receptors, which modulate the mesolimbic dopaminergic system, and provides a neurobiological basis for its efficacy.

Journal article

Wall MB, Birch D, Yong MY, 2016, Opportunities and considerations for visualising neuroimaging data on very large displays., F1000Res, Vol: 5, Pages: 2157-2157, ISSN: 2046-1402

Neuroimaging experiments can generate impressive volumes of data and many images of the results. This is particularly true of multi-modal imaging studies that use more than one imaging technique, or when imaging is combined with other assessments. A challenge for these studies is appropriate visualisation of results in order to drive insights and guide accurate interpretations. Next-generation visualisation technology therefore has much to offer the neuroimaging community. One example is the Imperial College London Data Observatory; a high-resolution (132 megapixel) arrangement of 64 monitors, arranged in a 313 degree arc, with a 6 metre diameter, powered by 32 rendering nodes. This system has the potential for high-resolution, large-scale display of disparate data types in a space designed to promote collaborative discussion by multiple researchers and/or clinicians. Opportunities for the use of the Data Observatory are discussed, with particular reference to applications in Multiple Sclerosis (MS) research and clinical practice. Technical issues and current work designed to optimise the use of the Data Observatory for neuroimaging are also discussed, as well as possible future research that could be enabled by the use of the system in combination with eye-tracking technology.

Journal article

Lawn W, Freeman TP, Pope RA, Joye A, Harvey L, Hindocha C, Mokrysz C, Moss A, Wall MB, Bloomfield MAP, Das RK, Morgan CJA, Nutt DJ, Curran HVet al., 2016, Acute and chronic effects of cannabinoids on effort-related decision-making and reward learning: an evaluation of the cannabis 'amotivational' hypotheses, Psychopharmacology, Vol: 233, Pages: 3537-3552, ISSN: 1432-2072

Rationale:Anecdotally, both acute and chronic cannabis use have been associated with apathy, amotivation, and other reward processing deficits. To date, empirical support for these effects is limited, and no previous studies have assessed both acute effects of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as associations with cannabis dependence.Objectives:The objectives of this study were (1) to examine acute effects of cannabis with CBD (Cann + CBD) and without CBD (Cann-CBD) on effort-related decision-making and (2) to examine associations between cannabis dependence, effort-related decision-making and reward learning.Methods:In study 1, 17 participants each received three acute vaporized treatments, namely Cann-CBD (8 mg THC), Cann + CBD (8 mg THC + 10 mg CBD) and matched placebo, followed by a 50 % dose top-up 1.5 h later, and completed the Effort Expenditure for Rewards Task (EEfRT). In study 2, 20 cannabis-dependent participants were compared with 20 non-dependent, drug-using control participants on the EEfRT and the Probabilistic Reward Task (PRT) in a non-intoxicated state.Results:Cann-CBD reduced the likelihood of high-effort choices relative to placebo (p = 0.042) and increased sensitivity to expected value compared to both placebo (p = 0.014) and Cann + CBD (p = 0.006). The cannabis-dependent and control groups did not differ on the EEfRT. However, the cannabis-dependent group exhibited a weaker response bias than the control group on the PRT (p = 0.007).Conclusions:Cannabis acutely induced a transient amotivational state and CBD influenced the effects of THC on expected value. In contrast, cannabis dependence was associated with preserved motivation alongside impaired reward learning, although confounding factors, including depression, cannot be disregarded. This is the first well powered, fully controlled study to objectively demonstrate the acute amotivational effects of THC.

Journal article

Freeman TP, Pope RA, Wall MB, Bisby J, Luijten M, Hindocha C, Lawn W, Mokrysz C, Moss A, Bloomfield MAP, Morgan CJA, Nutt DJ, Curran HVet al., 2016, Dissociable effects of cannabinoids on anticipatory and consummatory reward processing, 30th World Congress of the International-College-of-Neuropsychopharmacology (CINP), Publisher: OXFORD UNIV PRESS, Pages: 155-156, ISSN: 1461-1457

Conference paper

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