66 results found
Borissova A, Soni S, Aston ER, et 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 Alcohol Depend, Vol: 238
BACKGROUND: Adolescence is a period of psychological and neural development in which harms associated with cannabis use may be heightened. We hypothesised that adolescent who use cannabis (adolescentsWUC) would have steeper delay discounting (preference for immediate over future rewards) and greater demand (relative valuation) for cannabis than adults who use cannabis (adultsWUC). METHODS: This cross-sectional study, part of the 'CannTeen' project, compared adultsWUC (n = 71, 26-29 years old) and adolescentsWUC (n = 76, 16-17 years old), and gender- and age-matched adolescent (n = 63) and adult (n = 64) controls. AdolescentsWUC and adultsWUC used cannabis 1-7 days/week and were matched on cannabis use frequency (4 days/week). The Monetary Choice Questionnaire assessed delay discounting. A modified Marijuana Purchase Task (MPT) assessed cannabis demand in adolescentsWUC and adultsWUC. The MPT yielded five indices: intensity (amount of cannabis used at zero cost), Omax (total peak expenditure), Pmax (price at peak expenditure), breakpoint (cost at which cannabis demand is suppressed to zero) and elasticity (degree to which cannabis use decreases with increasing price). Analyses were adjusted for covariates of gender, socioeconomic status, other illicit drug use. RESULTS: Both adolescentsWUC and adultsWUC had steeper delay discounting than controls (F, (1,254)= 9.13, p = 0.003, ηp2= 0.04), with no significant age effect or interaction. AdolescentsWUC showed higher intensity (F, (1,138)= 9.76, p = 0.002, ηp2= 0.07) and lower elasticity (F, (1,138)= 15.25, p < 0.001, ηp2= 0.10) than adultsWUC. There were no significant differences in Pmax, Omax or breakpoint. CONCLUSION: Individuals who use cannabis prefer immediate rewards more than controls. AdolescentsWUC, compared to adultsWUC, may be in a high-risk category with diminished sensitivity to cannabis price
Wall MB, Freeman TP, Hindocha C, et 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
Bloomfield MAP, Yamamori Y, Hindocha C, et 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
Daws R, Timmermann C, Giribaldi B, et 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.
Skumlien M, Mokrysz C, Freeman TP, et al., 2022, Neural responses to reward anticipation and feedback in adult and adolescent cannabis users and controls, NEUROPSYCHOPHARMACOLOGY, ISSN: 0893-133X
Wall MB, Lam C, Ertl N, et 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>
Zafar RR, Erritzoe D, Wall MB, et 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
Mokrysz C, Shaban NDC, Freeman TP, et 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
Comninos A, Yang L, OCallaghan J, et 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.
Salem V, Demetriou L, Behary P, et 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.
Hannaway N, Lao-Kaim NP, Martin-Bastida A, et 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
Yang L, Demetriou L, Wall MB, et 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
Lawn W, Hill J, Hindocha C, et 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
Borissova A, Ferguson B, Wall MB, et 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
Botvinik-Nezer R, Holzmeister F, Camerer CF, et al., 2020, Variability in the analysis of a single neuroimaging dataset by many teams, NATURE, Vol: 582, Pages: 84-+, ISSN: 0028-0836
Yang L, Demetriou L, Wall M, et 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.
Mertens LJ, Wall MB, Roseman L, et 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
Mertens LJ, Wall MB, Roseman L, et 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
Nour MM, Dahoun T, McCutcheon RA, et 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.
Hannaway N, Lao-Kaim NP, Martin-Bastida A, et 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
Wall MB, Pope R, Freeman TP, et 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
Wall MB, 2019, Reliability starts with the experimental tools employed, CORTEX, Vol: 113, Pages: 352-354, ISSN: 0010-9452
Bloomfield MAP, Hindocha C, Green SF, et 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.
Roseman L, Demetriou L, Wall M, et 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.
Nour MM, Dahoun T, Schwartenbeck P, et 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
Comninos A, Demetriou L, Wall M, et 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.
Harvey J-L, Demetriou L, McGonigle J, et 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
Demetriou L, Kowalczyk OS, Tyson G, et 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
Nour M, Dahoun T, Schwartenbeck P, et 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
Carhart-Harris RL, Roseman L, Bolstridge M, et 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.
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