Imperial College London

DrMatthewWall

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Honorary Senior Lecturer
 
 
 
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matthew.wall

 
 
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Burlington DanesHammersmith Campus

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Summary

 

Publications

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88 results found

Wall MB, Lam C, Ertl N, Kaelen M, Roseman L, Nutt DJ, Carhart-Harris RLet al., 2023, Increased low-frequency brain responses to music after psilocybin therapy for depression., J Affect Disord, Vol: 333, Pages: 321-330

BACKGROUND: Psychedelic-assisted psychotherapy with psilocybin is an emerging therapy with great promise for depression, and modern psychedelic therapy (PT) methods incorporate music as a key element. Music is an effective emotional/hedonic stimulus that could also be useful in assessing changes in emotional responsiveness following PT. METHODS: Brain responses to music were assessed before and after PT using functional Magnetic Resonance Imaging (fMRI) and ALFF (Amplitude of Low Frequency Fluctuations) analysis methods. Nineteen patients with treatment-resistant depression underwent two treatment sessions involving administration of psilocybin, with MRI data acquired one week prior and the day after completion of psilocybin dosing sessions. RESULTS: Comparison of music-listening and resting-state scans revealed significantly greater ALFF in bilateral superior temporal cortex for the post-treatment music scan, and in the right ventral occipital lobe for the post-treatment resting-state scan. ROI analyses of these clusters revealed a significant effect of treatment in the superior temporal lobe for the music scan only. Voxelwise comparison of treatment effects showed relative increases for the music scan in the bilateral superior temporal lobes and supramarginal gyrus, and relative decreases in the medial frontal lobes for the resting-state scan. ALFF in these music-related clusters was significantly correlated with intensity of subjective effects felt during the dosing sessions. LIMITATIONS: Open-label trial. Relatively small sample size. CONCLUSIONS: These data suggest an effect of PT on the brain's response to music, implying an elevated responsiveness to music after psilocybin therapy that was related to subjective drug effects felt during dosing.

Journal article

Wall M, 2023, Shaking the kaleidoscope of the mind, Psychologist, Vol: 36, Pages: 40-44, ISSN: 0952-8229

Journal article

Mills E, Ertl N, Wall M, Thurston L, Yang L, Suladze S, Hunjan T, Phylactou M, Patel B, Muzi B, Ettehad D, Bassett P, Howard J, Rabiner E, Bech P, Abbara A, Goldmeier D, Comninos A, Dhillo Wet al., 2023, Effects of kisspeptin on sexual brain processing and penile tumescence in men with hypoactive sexual desire disorder: a randomized clinical trial, Jama Network Open, Vol: 6, Pages: 1-16, ISSN: 2574-3805

Importance The human physiological sexual response is crucial for reward, satisfaction, and reproduction. Disruption of the associated neurophysiological pathways predisposes to low sexual desire; the most prevalent psychological form is hypoactive sexual desire disorder (HSDD), which affects 8% of men but currently has no effective pharmacological treatment options. The reproductive neuropeptide kisspeptin offers a putative therapeutic target, owing to emerging understanding of its role in reproductive behavior.Objective To determine the physiological, behavioral, neural, and hormonal effects of kisspeptin administration in men with HSDD.Design, Setting, and Participants This double-blind, 2-way crossover, placebo-controlled randomized clinical trial was performed at a single academic research center in the UK. Eligible participants were right-handed heterosexual men with HSDD. Physiological, behavioral, functional magnetic resonance imaging (fMRI), and hormonal analyses were used to investigate the clinical and mechanistic effects of kisspeptin administration in response to visual sexual stimuli (short and long video tasks). The trial was conducted between January 11 and September 15, 2021, and data analysis was performed between October and November 2021.Interventions Participants attended 2 study visits at least 7 days apart, in balanced random order, for intravenous infusion of kisspeptin-54 (1 nmol/kg/h) for 75 minutes or for administration of a rate-matched placebo.Main Outcomes and Measures Changes in (1) brain activity on whole-brain analysis, as determined by fMRI blood oxygen level–dependent activity in response to visual sexual stimuli during kisspeptin administration compared with placebo, (2) physiological sexual arousal (penile tumescence), and (3) behavioral measures of sexual desire and arousal.Results Of the 37 men randomized, 32 completed the trial. Participants had a mean (SD) age of 37.9 (8.6) years and a mean (SD) body mass i

Journal article

Skumlien M, Freeman TP, Hall D, Mokrysz C, Wall MB, Ofori S, Petrilli K, Trinci K, Borissova A, Fernandez-Vinson N, Langley C, Sahakian BJ, Curran HV, Lawn Wet al., 2023, The Effects of Acute Cannabis With and Without Cannabidiol on Neural Reward Anticipation in Adults and Adolescents., Biol Psychiatry Cogn Neurosci Neuroimaging, Vol: 8, Pages: 219-229

BACKGROUND: Adolescents may respond differently to cannabis than adults, yet no previous functional magnetic resonance imaging study has examined acute cannabis effects in this age group. In this study, we investigated the neural correlates of reward anticipation after acute exposure to cannabis in adolescents and adults. METHODS: This was a double-blind, placebo-controlled, randomized, crossover experiment. Forty-seven adolescents (n = 24, 12 females, ages 16-17 years) and adults (n = 23, 11 females, ages 26-29 years) matched on cannabis use frequency (0.5-3 days/week) completed the Monetary Incentive Delay task during functional magnetic resonance imaging after inhaling cannabis with 0.107 mg/kg Δ⁹-tetrahydrocannabinol ("THC") (8 mg THC for a 75-kg person) or with THC plus 0.320 mg/kg cannabidiol ("THC+CBD") (24 mg CBD for a 75-kg person), or placebo cannabis. We investigated reward anticipation activity with whole-brain analyses and region of interest analyses in the right and left ventral striatum, right and left anterior cingulate cortex, and right insula. RESULTS: THC reduced anticipation activity compared with placebo in the right (p = .005, d= 0.49) and left (p = .003, d = 0.50) ventral striatum and the right insula (p = .01, d = 0.42). THC+CBD reduced activity compared with placebo in the right ventral striatum (p = .01, d = 0.41) and right insula (p = .002, d = 0.49). There were no differences between "THC" and "THC+CBD" conditions and no significant drug by age group interaction effect, supported by Bayesian analyses. There were no significant effects in the whole-brain analyses. CONCLUSIONS: In weekly cannabis users, cannabis suppresses the brain's anticipatory reward response to money, and CBD does not modulate this effect. Furthermore, the adolescent reward circuitry is not differentially sensitive to acute effects of cannabis on reward anticipation.

Journal article

Lawn W, Trinci K, Mokrysz C, Borissova A, Ofori S, Petrilli K, Bloomfield M, Haniff ZR, Hall D, Fernandez-Vinson N, Wang S, Englund A, Chesney E, Wall MB, Freeman TP, Curran HVet al., 2023, The acute effects of cannabis with and without cannabidiol in adults and adolescents: A randomised, double-blind, placebo-controlled, crossover experiment, Addiction, ISSN: 0965-2140

Background and Aims: Long-term harms of cannabis may be exacerbated in adolescence, but little is known about the acute effects of cannabis in adolescents. We aimed to (i) compare the acute effects of cannabis in adolescent and adult cannabis users and (ii) determine if cannabidiol (CBD) acutely modulates the effects of delta-9-tetrahydocannabinol (THC). Design: Randomised, double-blind, placebo-controlled, crossover experiment. The experiment was registered on ClinicalTrials.gov (NCT04851392). Setting: Laboratory in London, United Kingdom. Participants: Twenty-four adolescents (12 women, 16- to 17-year-olds) and 24 adults (12 women, 26- to 29-year-olds) who used cannabis 0.5–3 days/week and were matched on cannabis use frequency (mean = 1.5 days/week). Intervention: We administered three weight-adjusted vaporised cannabis flower preparations: ‘THC’ (8 mg THC for 75 kg person); ‘THC + CBD’ (8 mg THC and 24 mg CBD for 75 kg person); and ‘PLA’ (matched placebo). Measurements: Primary outcomes were (i) subjective ‘feel drug effect’; (ii) verbal episodic memory (delayed prose recall); and (iii) psychotomimetic effect (Psychotomimetic States Inventory). Findings: Compared with ‘PLA’, ‘THC’ and ‘THC + CBD’ significantly (P < 0.001) increased ‘feel drug effect’ (mean difference [MD] = 6.3, 95% CI = 5.3–7.2; MD = 6.8, 95% CI = 6.0–7.7), impaired verbal episodic memory (MD = –2.7, 95% CI = −4.1 to −1.4; MD = −2.9, 95% CI = −4.1 to −1.7) and increased psychotomimetic effects (MD = 7.8, 95% CI = 2.8–12.7; MD = 10.8, 95% CI = 6.2–15.4). There was no evidence that adolescents differed from adults in their responses to cannabis (interaction P ≥ 0.4). Bayesian analyses supported equivalent effects of cannabis in adolescents and adults (Bayes factor [BF01] >3). There was no evide

Journal article

Zahid U, Onwordi EC, Hedges EP, Wall MB, Modinos G, Murray RM, Egerton Aet al., 2022, Neurofunctional correlates of glutamate and GABA imbalance in psychosis: A systematic review, NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, Vol: 144, ISSN: 0149-7634

Journal article

Lawn W, Mokrysz C, Lees R, Trinci K, Petrilli K, Skumlien M, Borissova A, Ofori S, Bird C, Jones G, Bloomfield MA, Das RK, Wall MB, Freeman TP, Curran HVet al., 2022, The CannTeen Study: Cannabis use disorder, depression, anxiety, and psychotic-like symptoms in adolescent and adult cannabis users and age-matched controls., J Psychopharmacol, Vol: 36, Pages: 1350-1361

BACKGROUND: Adolescence is characterised by psychological and neural development. Cannabis harms may be accentuated during adolescence. We hypothesised that adolescents would be more vulnerable to the associations between cannabis use and mental health and addiction problems than adults. METHOD: As part of the 'CannTeen' study, we conducted a cross-sectional analysis. There were 274 participants: split into groups of adolescent users (n = 76; 16-17 years old) and controls (n = 63), and adult users (n = 71; 26-29 years old) and controls (n = 64). Among users, cannabis use frequency ranged from 1 to 7 days/week, while controls had 0-10 lifetime exposures to cannabis. Adolescent and adult cannabis users were matched on cannabis use frequency (mean=4 days/week). We measured Diagnostic and Statistical Manual (DSM-5) Cannabis Use Disorder (CUD), Beck Depression Inventory, Beck Anxiety Inventory and Psychotomimetic States Inventory-adapted. RESULTS: After adjustment for covariates, adolescent users were more likely to have severe CUD than adult users (odd ratio = 3.474, 95% confidence interval (CI) = 1.501-8.036). Users reported greater psychotic-like symptoms than controls (b = 6.004, 95% CI = 1.211-10.796) and adolescents reported greater psychotic-like symptoms than adults (b = 5.509, 95% CI = 1.070-9.947). User-group was not associated with depression or anxiety. No significant interactions between age-group and user-group were identified. Exploratory analyses suggested that cannabis users with severe CUD had greater depression and anxiety levels than cannabis users without severe CUD. CONCLUSION: Adolescent cannabis users are more likely than adult cannabis users to have severe CUD. Adolescent cannabis users have greater psychotic-like symptoms than adult cannabis users and adolescent controls, through an addi

Journal article

Shukuroglou M, Roseman L, Wall M, Nutt D, Kaelen M, Carhart-Harris Ret al., 2022, Changes in music-evoked emotion and ventral striatal functional connectivity after psilocybin therapy for depression, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 37, Pages: 70-79, ISSN: 0269-8811

Journal article

Richie-Halford A, Cieslak M, Ai L, Caffarra S, Covitz S, Franco AR, Karipidis II, Kruper J, Milham M, Avelar-Pereira B, Roy E, Sydnor VJ, Yeatman JD, Fibr Community Science Consortium, Satterthwaite TD, Rokem Aet al., 2022, Author Correction: An analysis-ready and quality controlled resource for pediatric brain white-matter research., Sci Data, Vol: 9

Journal article

Richie-Halford A, Cieslak M, Ai L, Caffarra S, Covitz S, Franco AR, Karipidis II, Kruper J, Milham M, Avelar-Pereira B, Roy E, Sydnor VJ, Yeatman JD, Fibr Community Science Consortium, Satterthwaite TD, Rokem Aet al., 2022, Publisher Correction: An analysis-ready and quality controlled resource for pediatric brain white-matter research., Sci Data, Vol: 9

Journal article

Thurston L, Hunjan T, Ertl N, Wall M, Mills E, Suladze S, Patel B, Alexander E, Muzi B, Bassett P, Rabiner E, Bech P, Goldmeier D, Abbara A, Comninos A, Dhillo Wet al., 2022, Effects of kisspeptin administration in women with hypoactive sexual desire disorder: a randomized clinical trial, Jama Network Open, Vol: 5, Pages: 1-14, ISSN: 2574-3805

Importance: The absence or deficiency of sexual desire leading to distress or interpersonal difficultydefines ‘hypoactive sexual desire disorder’ (HSDD). Despite being the most common female sexualhealth complaint worldwide, current treatment options for HSDD are limited in their safety andeffectiveness. The hormone kisspeptin is a key endogenous activator of the reproductive hormonalaxis with additional emerging roles in sexual and emotional behavior, however, its effects in womenwith HSDD are unknown.Objective: To test the hypothesis that kisspeptin enhances sexual and attraction brain processing inwomen with HSDD.Design: A randomized, double-blind, two-way crossover, placebo-controlled clinical trial. Functionalneuroimaging, psychometric and hormonal analyses were employed to investigate the effects ofkisspeptin administration on brain processing, in response to erotic stimuli (erotic videos) and facialattraction (face images of varying attractiveness).Setting: The trial was conducted in a university research setting from October 2020 to April 2021. Datawere analyzed from May to December 2021.Participants: 32 premenopausal women with HSDD for at least 6 months’ duration.Interventions: 75-minute intravenous infusion of kisspeptin-54 (1 nmol/kg/h) vs equivalent-rateplacebo infusion.Main Outcome and Measures: Blood oxygen level–dependent responses across the whole brain andregions of interest during kisspeptin vs placebo administration, in response to erotic and facialattraction stimuli.Results: Of the 40 participants who were randomized, 32 women completed both kisspeptin andplacebo visits, and the mean (SEM) age was 29.2 (1.2) years. Kisspeptin administration resulted inmodulations in sexual and facial attraction brain processing (all P<.05). Furthermore, positivecorrelations were observed between kisspeptin-enhanced hippocampal activity in response to eroticvideos, and baseline distress relating to sexual function (P<.01). In additio

Journal article

Richie-Halford A, Cieslak M, Ai L, Caffarra S, Covitz S, Franco AR, Karipidis II, Kruper J, Milham M, Avelar-Pereira B, Roy E, Sydnor VJ, Yeatman JD, Satterthwaite TD, Rokem A, Abbott NJ, Abbott NJ, Anderson JAE, Gagana B, Bleile M, Bloomfield PS, Bottom V, Bourque J, Boyle R, Brynildsen JK, Calarco N, Castrellon JJ, Chaku N, Chen B, Chopra S, Coffey EBJ, Colenbier N, Cox DJ, Crippen JE, Crouse JJ, David S, Leener BD, Delap G, Deng Z-D, Dugre JR, Eklund A, Ellis K, Ered A, Farmer H, Faskowitz J, Finch JE, Flandin G, Flounders MW, Fonville L, Frandsen SB, Garic D, Garrido-Vasquez P, Gonzalez-Escamilla G, Grogans SE, Grotheer M, Gruskin DC, Guberman GI, Haggerty EB, Hahn Y, Hall EH, Hanson JL, Harel Y, Vieira BH, Hettwer MD, Hobday H, Horien C, Huang F, Huque ZM, James AR, Kahhale I, Kamhout SLH, Keller AS, Khera HS, Kiar G, Kirk PA, Kohl SH, Korenic SA, Korponay C, Kozlowski AK, Kraljevic N, Lazari A, Leavitt MJ, Li Z, Liberati G, Lorenc ES, Lossin AJ, Lotter LD, Lydon-Staley DM, Madan CR, Magielse N, Marusak HA, Mayor J, McGowan AL, Mehta KP, Meisler SL, Michael C, Mitchell ME, Morand-Beaulieu S, Newman BT, Nielsen JA, O'Mara SM, Ojha A, Omary A, ozarslan E, Parkes L, Peterson M, Pines AR, Pisanu C, Rich RR, Sahoo AK, Samara A, Sayed F, Schneider JT, Shaffer LS, Shatalina E, Sims SA, Sinclair S, Song JW, Hogrogian GS, Tooley UA, Tripathi V, Turker HB, Valk SL, Wall MB, Walther CK, Wang Y, Wegmann B, Welton T, Wiesman AI, Wiesman AG, Wiesman M, Winters DE, Yuan R, Zacharek SJ, Zajner C, Zakharov I, Zammarchi G, Zhou D, Zimmerman B, Zoner K, Satterthwaite TD, Rokem Aet al., 2022, An analysis-ready and quality controlled resource for pediatric brain white-matter research, SCIENTIFIC DATA, Vol: 9

Journal article

Thurston L, Hunjan T, Mills E, Wall M, Ertl N, Phylactou M, Muzi B, Patel B, Alexander E, Suladze S, Modi M, Eng P, Bassett P, Abbara A, Goldmeier D, Comninos A, Dhillo Wet al., 2022, Melanocortin 4 receptor agonism enhances sexual brain processing in women with hypoactive sexual desire disorder, Journal of Clinical Investigation, Vol: 132, Pages: 1-12, ISSN: 0021-9738

BACKGROUND. Hypoactive sexual desire disorder (HSDD) is characterized by a persistent deficiency of sexual fantasies and desire for sexual activity, causing marked distress and interpersonal difficulty. It is the most prevalent female sexual health problem globally, affecting approximately 10% of women, but has limited treatment options. Melanocortin 4 receptor (MC4R) agonists have emerged as a promising therapy for women with HSDD, through unknown mechanisms. Studying the pathways involved is crucial for our understanding of normal and abnormal sexual behavior.METHODS. Using psychometric, functional neuroimaging, and hormonal analyses, we conducted a randomized, double-blinded, placebo-controlled, crossover clinical study to assess the effects of MC4R agonism compared with placebo on sexual brain processing in 31 premenopausal heterosexual women with HSDD.RESULTS. MC4R agonism significantly increased sexual desire for up to 24 hours after administration compared with placebo. During functional neuroimaging, MC4R agonism enhanced cerebellar and supplementary motor area activity and deactivated the secondary somatosensory cortex, specifically in response to visual erotic stimuli, compared with placebo. In addition, MC4R agonism enhanced functional connectivity between the amygdala and the insula during visual erotic stimuli compared with placebo.CONCLUSION. These data suggest that MC4R agonism enhanced sexual brain processing by reducing self-consciousness, increasing sexual imagery, and sensitizing women with HSDD to erotic stimuli. These findings provide mechanistic insight into the action of MC4R agonism in sexual behavior and are relevant to the ongoing development of HSDD therapies and MC4R agonist development more widely.TRIAL REGISTRATION. ClinicalTrials.gov NCT04179734.FUNDING. This is an investigator-sponsored study funded by AMAG Pharmaceuticals Inc., the Medical Research Council (MRC) (MR/T006242/1), and the National Institute for Health Research (NIHR) (C

Journal article

Skumlien M, Mokrysz C, Freeman TP, Valton V, Wall MB, Bloomfield M, Lees R, Borissova A, Petrilli K, Giugliano M, Clisu D, Langley C, Sahakian BJ, Curran HV, Lawn Wet al., 2022, Anhedonia, Apathy, Pleasure, and Effort-Based Decision-Making in Adult and Adolescent Cannabis Users and Controls, INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, Vol: 26, Pages: 9-19, ISSN: 1461-1457

Journal article

Wall MB, 2022, "Technical skills are always useful, no matter what you're actually working on", Academia and the World Beyond: Navigating Life after a PhD, Pages: 23-29, ISBN: 9783030826055

In our interview with Matthew Wall, we learn about the potential to work in a position that bridges between commercial and academic research. Using the cognitive neuroscience approach of functional magnetic resonance imaging (fMRI), Matt conducts research on the effects of drugs on the brain. After a difficult PhD studying implicit learning and resulting in no publications, technical experience with fMRI and programming acquired during his PhD laid the foundation for his career. While it is useful to have a career plan, you also need to be flexible and realistic about your options. Strong research skills and an interest in methods are valuable and could lead to a path like Matt's.

Book chapter

Borissova A, Soni S, Aston ER, Lees R, Petrilli K, Wall MB, Bloomfield MAP, Mertzani E, Paksina A, Freeman TP, Mokrysz C, Lawn W, Curran HVet al., 2022, Age differences in the behavioural economics of cannabis use: Do adolescents and adults differ on demand for cannabis and discounting of future reward?, DRUG AND ALCOHOL DEPENDENCE, Vol: 238, ISSN: 0376-8716

Journal article

Lawn W, Fernandez-Vinson N, Mokrysz C, Hogg G, Lees R, Trinci K, Petrilli K, Borissova A, Ofori S, Waters S, Michór P, Wall MB, Freeman TP, Curran HVet al., 2022, Correction to: The CannTeen study: verbal episodic memory, spatial working memory, and response inhibition in adolescent and adult cannabis users and age‑matched controls., Psychopharmacology (Berl), Vol: 239

Journal article

Wall MB, Freeman TP, Hindocha C, Demetriou L, Ertl N, Freeman AM, Jones APM, Lawn W, Pope R, Mokrysz C, Solomons D, Statton B, Walker HR, Yamamori Y, Yang Z, Yim JLL, Nutt DJ, Howes OD, Curran HV, Bloomfield MAPet al., 2022, Individual and combined effects of cannabidiol and Delta(9)-tetrahydrocannabinol on striato-cortical connectivity in the human brain, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 36, Pages: 732-744, ISSN: 0269-8811

Journal article

Lawn W, Fernandez-Vinson N, Mokrysz C, Hogg G, Lees R, Trinci K, Petrilli K, Borissova A, Ofori S, Waters S, Michór P, Wall MB, Freeman TP, Curran HVet al., 2022, The CannTeen study: verbal episodic memory, spatial working memory, and response inhibition in adolescent and adult cannabis users and age-matched controls., Psychopharmacology (Berl), Vol: 239, Pages: 1629-1641

BACKGROUND: Preclinical and human studies suggest that adolescent cannabis use may be associated with worse cognitive outcomes than adult cannabis use. We investigated the associations between chronic cannabis use and cognitive function in adolescent and adult cannabis users and controls. We hypothesised user-status would be negatively associated with cognitive function and this relationship would be stronger in adolescents than adults. METHODS: As part of the 'CannTeen' project, this cross-sectional study assessed cognitive performance in adolescent cannabis users (n = 76; 16-17-year-olds), adolescent controls (n = 63), adult cannabis users (n = 71; 26-29-year-olds) and adult controls (n = 64). Users used cannabis 1-7 days/week. Adolescent and adult cannabis users were matched on cannabis use frequency (4 days/week) and time since last use (2.5 days). Verbal episodic memory (VEM) was assessed using the prose recall task, spatial working memory (SWM) was assessed using the spatial n-back task, and response inhibition was assessed with the stop-signal task. Primary outcome variables were: delayed recall, 3-back discriminability, and stop signal reaction time, respectively. RESULTS: Users had worse VEM than controls (F(1,268) = 7.423, p = 0.007). There were no significant differences between user-groups on SWM or response inhibition. Null differences were supported by Bayesian analyses. No significant interactions between age-group and user-group were found for VEM, SWM, or response inhibition. CONCLUSIONS: Consistent with previous research, there was an association between chronic cannabis use and poorer VEM, but chronic cannabis use was not associated with SWM or response inhibition. We did not find evidence for heightened adolescent vulnerability to cannabis-related cognitive impairment.

Journal article

Bloomfield MAP, Yamamori Y, Hindocha C, Jones APM, Yim JLL, Walker HR, Statton B, Wall MB, Lees RH, Howes OD, Curran VH, Roiser JP, Freeman TPet al., 2022, The acute effects of cannabidiol on emotional processing and anxiety: a neurocognitive imaging study, PSYCHOPHARMACOLOGY, Vol: 239, Pages: 1539-1549, ISSN: 0033-3158

Journal article

Daws R, Timmermann C, Giribaldi B, Sexton J, Wall M, Erritzoe D, Roseman L, Nutt D, Carhart-Harris Ret al., 2022, Increased global integration in the brain after psilocybin therapy for depression, Nature Medicine, Vol: 28, ISSN: 1078-8956

Psilocybin therapy shows antidepressant potential, but its therapeutic actions are not well understood. We assessed the sub-acute impact of psilocybin on brain function in two clinical trials of depression. The first was an open-label trial of orally administered psilocybin (10mg and 25mg, 7 days apart) in treatment-resistant depression (TRD). fMRI was recorded at baseline and one day after the 25mg dose. Beck’s depression inventory (BDI) was the primary outcome measure (MR/J00460X/1). The second trial was a double-blind phase 2 randomised control trial (DB-RCT) comparing psilocybin therapy with escitalopram. Major depressive disorder (MDD) patients received either: 2 x 25mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily placebo (‘psilocybin-arm’); or 2 x 1mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily escitalopram [10-20mg] (‘escitalopram-arm’). fMRI wasrecorded at baseline and 3 weeks after the 2nd psilocybin dose (NCT03429075). In both trials, the antidepressant response to psilocybin was rapid, sustained and correlated with decreases in functional MRI (fMRI) brain network modularity, implying that psilocybin’s antidepressant action may depend on a global increase in brainnetwork integration. Network cartography analyses indicated that 5-HT2A receptor rich higher-order functional networks became more functionally inter-connected and flexible post psilocybin. The antidepressant response to escitalopram was milder and no changes in brain network organisation were observed. Consistent efficacy related brain changes, correlating with robust antidepressant effects across two studies, suggest an antidepressant mechanism for psilocybin therapy: Global increases in brain network integration.

Journal article

Skumlien M, Mokrysz C, Freeman TP, Wall MB, Bloomfield M, Lees R, Borissova A, Petrilli K, Carson J, Coughlan T, Ofori S, Langley C, Sahakian BJ, Curran HV, Lawn Wet al., 2022, Neural responses to reward anticipation and feedback in adult and adolescent cannabis users and controls, NEUROPSYCHOPHARMACOLOGY, Vol: 47, Pages: 1976-1983, ISSN: 0893-133X

Journal article

Wall MB, Lam C, Ertl N, Kaelen M, Roseman L, Nutt DJ, Carhart-Harris RLet al., 2022, Increased low-frequency brain responses to music after psilocybin therapy for depression

<jats:title>Abstract</jats:title><jats:p>Psychedelic-assisted psychotherapy with psilocybin is an emerging therapy with great promise for depression, and modern psychedelic therapy (PT) methods incorporate music as a key element. Music is an effective emotional/hedonic stimulus that could also be useful in assessing changes in emotional responsiveness following psychedelic therapy. Brain responses to music were assessed before and after PT using functional Magnetic Resonance Imaging (fMRI) and ALFF (Amplitude of Low Frequency Fluctuations) analysis methods. Nineteen patients with treatment-resistant depression underwent two treatment sessions involving administration of psilocybin, with MRI data acquired one week prior and the day after completion of the second of two psilocybin dosing sessions. Comparison of music-listening and resting-state scans revealed significantly greater ALFF in bilateral superior temporal cortex for the post-treatment music scan, and in the right ventral occipital lobe for the post-treatment resting-state scan. ROI analyses of these clusters revealed a significant effect of treatment in the superior temporal lobe for the music scan only. Somewhat consistently, voxelwise comparison of treatment effects showed relative increases for the music scan in the bilateral superior temporal lobes and supramarginal gyrus, and relative decreases in the medial frontal lobes for the resting-state scan. ALFF in these music-related clusters was significantly correlated with intensity of subjective effects felt during the dosing sessions. These data suggest a specific effect of PT on the brain’s response to a hedonic stimulus (music), implying an elevated responsiveness to music after psilocybin therapy that was related to subjective drug effects felt during dosing.</jats:p>

Journal article

Zafar RR, Erritzoe D, Wall MB, Myers J, Nutt DJet al., 2021, Dopamine D3 Receptor antagonism in alcohol dependence: A case-control functional Imaging study, 34th European-College-of-Neuropsychopharmacology (ECNP) Congress on Early Career Scientists in Europe, Publisher: ELSEVIER, Pages: S448-S449, ISSN: 0924-977X

Conference paper

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

Daws R, Timmerman C, Giribaldi B, Sexton J, Wall M, Erritzoe D, Roseman L, Nutt D, Carhart-Harris Ret al., 2021, Decreased brain modularity after psilocybin therapy for depression.

<jats:title>Abstract</jats:title> <jats:p><jats:bold>Importance </jats:bold>Psilocybin therapy shows antidepressant potential; our data link its antidepressant effects to decreased brain network modularity post-treatment. <jats:bold>Objective </jats:bold>To assess the sub-acute impact of psilocybin on brain activity in patients with depression. <jats:bold>Design </jats:bold>Pre vs post-treatment resting-state functional MRI (fMRI) was recorded in two trials: 1) Open-label treatment-resistant depression (TRD) trial with baseline vs 1 day post-treatment fMRI (April-2015 to April-2016); 2) Two-arm double-blind RCT in major depressive disorder (MDD), fMRI baseline vs 3 week after psilocybin-therapy or 6 weeks of daily escitalopram (January-2019 to March-2020). <jats:bold>Setting </jats:bold>Study visits occurred at the NIHR Imperial Clinical Research Facility.<jats:bold>Participants </jats:bold>Adult male and female patients with TRD or MDD. <jats:bold>Intervention(s) (for clinical trials) or Exposure(s) (for observational studies)</jats:bold>Study 1: Two oral doses of psilocybin (10mg and 25mg, fixed order, 7 days apart). fMRI was recorded at baseline and one day after the 25mg dose. Study 2: either: 2 x 25mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily placebo (‘psilocybin-arm’), or 2 x 1mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily escitalopram [10-20mg] (‘escitalopram-arm’). fMRI was recorded at baseline and 3 weeks after the 2nd psilocybin dose, which was the final day of the 6-week daily capsule ingestion. <jats:bold>Main Outcome(s) and Measure(s) </jats:bold>Beck Depression Inventory and fMRI network modularity. <jats:bold> </jats:bold><jats:bold>Results </jats:bold>Study 1: In 16 adults (mean age [SD], 42.8 [10.1] years, 4 [25%] female), psilocybin therapy<jats:underline> </ja

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

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