Publications
96 results found
Kaelen M, Lorenz R, Barrett F, et al., 2017, Effects of LSD on music-evoked brain activity
<jats:title>Abstract</jats:title><jats:p>Music is a highly dynamic stimulus, and consists of distinct acoustic features, such as pitch, rhythm and timbre. Neuroimaging studies highlight a hierarchy of brain networks involved in music perception. Psychedelic drugs such as lysergic acid diethylamide (LSD) temporary disintegrate the normal hierarchy of brain functioning, and produce profound subjective effects, including enhanced music-evoked emotion. The primary objective of this study was to investigate the acute effects of LSD on music-evoked brain-activity under naturalistic music listening conditions. 16 healthy participants were enrolled in magnetic resonance imaging (fMRI) while listening to a 7-minute music piece under eyes-closed conditions on two separate visits (LSD (75 mcg) and placebo). Dynamic time courses for acoustic features were extracted from the music excerpts, and were entered into subject-level fMRI analyses as regressors of interest. Differences between conditions were assessed at group level subsequently, and were related to changes in music-evoked emotions via correlation analyses. Psycho-physiological interactions (PPIs) were carried out to further interrogate underlying music-specific changes in functional connectivity under LSD. Results showed pronounced cortical and subcortical changes in music-evoked brain activity under LSD. Most notable changes in brain activity and connectivity were associated with the component timbral complexity, representing the complexity of the music’s spectral distribution, and these occurred in brain networks previously identified for music-perception and music-evoked emotion, and showed an association with enhanced music-evoked feelings of wonder under LSD. The findings shed light on how the brain processes music under LSD, and provide a neurobiological basis for the usefulness of music in psychedelic therapy.</jats:p>
Comninos A, Wall M, Demetriou L, et 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.
Quelch D, Mick I, McGonigle J, et 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.
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.
Lawn W, Freeman TP, Pope RA, et 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.
Freeman TP, Pope RA, Wall MB, et 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
Freeman TP, Pope RA, Wall MB, et al., 2016, PM298. Dissociable effects of cannabinoids on anticipatory and consummatory reward processing, The international journal of neuropsychopharmacology, Vol: 19, Pages: 6-7, ISSN: 1461-1457
Kaelen M, Roseman L, Kahan J, et al., 2016, LSD modulates music-induced imagery via changes in parahippocampal connectivity, European Neuropsychopharmacology, Vol: 26, Pages: 1099-1109, ISSN: 1873-7862
Psychedelic drugs such as lysergic acid diethylamide (LSD) were used extensively in psychiatry in the past and their therapeutic potential is beginning to be re-examined today. Psychedelic psychotherapy typically involves a patient lying with their eyes-closed during peak drug effects, while listening to music and being supervised by trained psychotherapists. In this context, music is considered to be a key element in the therapeutic model; working in synergy with the drug to evoke therapeutically meaningful thoughts, emotions and imagery. The underlying mechanisms involved in this process have, however, never been formally investigated. Here we studied the interaction between LSD and music-listening on eyes-closed imagery by means of a placebo-controlled, functional magnetic resonance imaging (fMRI) study. Twelve healthy volunteers received intravenously administered LSD (75µg) and, on a separate occasion, placebo, before being scanned under eyes-closed resting conditions with and without music-listening. The parahippocampal cortex (PHC) has previously been linked with (1) music-evoked emotion, (2) the action of psychedelics, and (3) mental imagery. Imaging analyses therefore focused on changes in the connectivity profile of this particular structure. Results revealed increased PHC-visual cortex (VC) functional connectivity and PHC to VC information flow in the interaction between music and LSD. This latter result correlated positively with ratings of enhanced eyes-closed visual imagery, including imagery of an autobiographical nature. These findings suggest a plausible mechanism by which LSD works in combination with music listening to enhance certain subjective experiences that may be useful in a therapeutic context.
Bishop CA, Johnson SM, Wall MB, et al., 2016, Magnetic resonance imaging reveals the complementary effects of decongestant and Breathe Right Nasal Strips on internal nasal anatomy, Laryngoscope, ISSN: 1531-4995
OBJECTIVES/HYPOTHESIS: This magnetic resonance imaging (MRI) study of 26 subjects with nasal congestion was performed to assess in the complete nasal passage both the anatomical effect of the marketed Breathe Right Nasal Strip (BRNS) relative to placebo and the potential adjunctive effect of using a decongestant in combination with the BRNS. STUDY DESIGN: Randomized, crossover study. METHODS: The study consisted of two parts, the first involving application of either the BRNS or the placebo strip in a randomized, crossover design with evaluator blinding, and repeated MRI scanning; and the second a sequential process of decongestant administration, MRI scanning, application of the BRNS, and repeated MRI. The same anatomical MRI protocol was used throughout. Nasal patency was assessed in the whole nasal passage and eight subregions (by inferior-superior, anterior-posterior division). Numerical response scores representing subjective nasal congestion were also obtained. RESULTS: Results demonstrate significant anatomical enlargement with the BRNS relative to placebo (P < .001), as well as an additive effect of using a decongestant in combination with the BRNS; both supported by a strong and significant negative correlation with the subjective nasal response measures of nasal congestion (r = -0.98, P = .002). Furthermore, analysis of the nasal subregions indicates that this adjunctive effect arises from a partially localized action of the complementary products: the BRNS acting primarily anteriorly in the nose and the decongestant mainly posteriorly. CONCLUSIONS: The BRNS alone significantly increases nasal patency and alleviates perceived nasal congestion, and additional relief of symptoms can be obtained with simultaneous use of a decongestant. LEVEL OF EVIDENCE: 1b. Laryngoscope, 2016.
Maron E, Wall M, Norbury R, et al., 2015, Effect of short-term escitalopram treatment on neural activation during emotional processing, Journal of Psychopharmacology, Vol: 30, Pages: 33-39, ISSN: 1461-7285
Recent functional magnetic resonance (fMRI) imaging studies have revealed that subchronic medication with escitalopram leads to significantreduction in both amygdala and medial frontal gyrus reactivity during processing of emotional faces, suggesting that escitalopram may have adistinguishable modulatory effect on neural activation as compared with other serotonin-selective antidepressants. In this fMRI study we aimed toexplore whether short-term medication with escitalopram in healthy volunteers is associated with reduced neural response to emotional processing,and whether this effect is predicted by drug plasma concentration. The neural response to fearful and happy faces was measured before and on day7 of treatment with escitalopram (10mg) in 15 healthy volunteers and compared with those in a control unmedicated group (n=14). Significantlyreduced activation to fearful, but not to happy facial expressions was observed in the bilateral amygdala, cingulate and right medial frontal gyrusfollowing escitalopram medication. This effect was not correlated with plasma drug concentration. In accordance with previous data, we showed thatescitalopram exerts its rapid direct effect on emotional processing via attenuation of neural activation in pathways involving medial frontal gyrus andamygdala, an effect that seems to be distinguishable from that of other SSRIs.
Colasanti A, Guo, Giannetti P, et al., 2015, Hippocampal neuroinflammation, functional connectivity and depressive symptoms in multiple sclerosis, Biological Psychiatry, Vol: 80, Pages: 62-72, ISSN: 1873-2402
BackgroundDepression, a condition commonly comorbid with multiple sclerosis (MS), is associated more generally with elevated inflammatory markers and hippocampal pathology. We hypothesized that neuroinflammation in the hippocampus is responsible for depression associated with MS. We characterized the relationship between depressive symptoms and hippocampal microglial activation in patients with MS using the 18-kDa translocator protein radioligand [18F]PBR111. To evaluate pathophysiologic mechanisms, we explored the relationships between hippocampal neuroinflammation, depressive symptoms, and hippocampal functional connectivities defined by resting-state functional magnetic resonance imaging.MethodsThe Beck Depression Inventory (BDI) was administered to 11 patients with MS and 22 healthy control subjects before scanning with positron emission tomography and functional magnetic resonance imaging. We tested for higher [18F]PBR111 uptake in the hippocampus of patients with MS relative to healthy control subjects and examined the correlations between [18F]PBR111 uptake, BDI scores, and hippocampal functional connectivities in the patients with MS.ResultsPatients with MS had an increased hippocampal [18F]PBR111 distribution volume ratio relative to healthy control subjects (p = .024), and the hippocampal distribution volume ratio was strongly correlated with the BDI score in patients with MS (r = .86, p = .006). Hippocampal functional connectivities to the subgenual cingulate and prefrontal and parietal regions correlated with BDI scores and [18F]PBR111 distribution volume ratio.ConclusionsOur results provide evidence that hippocampal microglial activation in MS impairs the brain functional connectivities in regions contributing to maintenance of a normal affective state. Our results suggest a rationale for the responsiveness of depression in some patients with MS to effective control of brain neuroinflammation. Our findings also lend support to further investigation of t
Carhart-Harris RL, Murphy K, Leech R, et al., 2015, The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labeling and Blood Oxygen Level-Dependent Resting State Functional Connectivity, Biological Psychiatry, Vol: 78, Pages: 554-562, ISSN: 1873-2402
BackgroundThe compound 3,4-methylenedioxymethamphetamine (MDMA) is a potent monoamine releaser that produces an acute euphoria in most individuals.MethodsIn a double-blind, placebo-controlled, balanced-order study, MDMA was orally administered to 25 physically and mentally healthy individuals. Arterial spin labeling and seed-based resting state functional connectivity (RSFC) were used to produce spatial maps displaying changes in cerebral blood flow (CBF) and RSFC after MDMA administration. Participants underwent two arterial spin labeling and two blood oxygen level–dependent scans in a 90-minute scan session; MDMA and placebo study days were separated by 1 week.ResultsMarked increases in positive mood were produced by MDMA. Decreased CBF only was observed after MDMA, and this was localized to the right medial temporal lobe (MTL), thalamus, inferior visual cortex, and the somatosensory cortex. Decreased CBF in the right amygdala and hippocampus correlated with ratings of the intensity of global subjective effects of MDMA. The RSFC results complemented the CBF results, with decreases in RSFC between midline cortical regions, the medial prefrontal cortex, and MTL regions, and increases between the amygdala and hippocampus. There were trend-level correlations between these effects and ratings of intense and positive subjective effects.ConclusionsThe MTLs appear to be specifically implicated in the mechanism of action of MDMA, but further work is required to elucidate how the drug’s characteristic subjective effects arise from its modulation of spontaneous brain activity.
Datta G, Battaglini M, Scott G, et al., 2015, Positron emission tomography imaging in multiple sclerosis highlights a diffuse inflammatory response in brain that appears normal on conventional magnetic resonance imaging, 31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE Publications (UK and US), Pages: 477-478, ISSN: 1477-0970
Bourke JH, Wall MB, 2015, phMRI: methodological considerations for mitigating potential confounding factors, Frontiers in Neuroscience, Vol: 9, ISSN: 1662-4548
Pharmacological Magnetic Resonance Imaging (phMRI) is a variant of conventional MRI that adds pharmacological manipulations in order to study the effects of drugs, or uses pharmacological probes to investigate basic or applied (e.g., clinical) neuroscience questions. Issues that may confound the interpretation of results from various types of phMRI studies are briefly discussed, and a set of methodological strategies that can mitigate these problems are described. These include strategies that can be employed at every stage of investigation, from study design to interpretation of resulting data, and additional techniques suited for use with clinical populations are also featured. Pharmacological MRI is a challenging area of research that has both significant advantages and formidable difficulties, however with due consideration and use of these strategies many of the key obstacles can be overcome.
Stewart LH, Ferguson B, Morgan CJA, et al., 2014, Effects of ecstasy on cooperative behaviour and perception of trustworthiness: A naturalistic study, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 28, Pages: 1001-1008, ISSN: 0269-8811
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- Citations: 14
Carhart-Harris RL, Wall MB, Erritzoe D, et al., 2014, The effect of acutely administered MDMA on subjective and BOLD-fMRI responses to favourite and worst autobiographical memories, INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, Vol: 17, Pages: 527-540, ISSN: 1461-1457
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- Citations: 59
Hammett ST, Smith AT, Wall MB, et al., 2013, Implicit representations of luminance and the temporal structure of moving stimuli in multiple regions of human visual cortex revealed by multivariate pattern classification analysis, JOURNAL OF NEUROPHYSIOLOGY, Vol: 110, Pages: 688-699, ISSN: 0022-3077
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- Citations: 6
Smith AT, Wall MB, Thilo KV, 2012, Vestibular Inputs to Human Motion-Sensitive Visual Cortex, CEREBRAL CORTEX, Vol: 22, Pages: 1068-1077, ISSN: 1047-3211
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- Citations: 95
Glover S, Wall MB, Smith AT, 2012, Distinct cortical networks support the planning and online control of reaching-to-grasp in humans, EUROPEAN JOURNAL OF NEUROSCIENCE, Vol: 35, Pages: 909-915, ISSN: 0953-816X
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- Citations: 50
Durant S, Wall MB, Zanker JM, 2011, Manipulating the content of dynamic natural scenes to characterize response in human MT/MST, JOURNAL OF VISION, Vol: 11, ISSN: 1534-7362
Durant S, Wall MB, Zanker JM, 2011, Manipulating the content of dynamic natural scenes to characterize response in human MT/MST, JOURNAL OF VISION, Vol: 11, ISSN: 1534-7362
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- Citations: 2
Hammett ST, Wall MB, Edwards TC, et al., 2010, Dietary supplementation of creatine monohydrate reduces the human fMRI BOLD signal, NEUROSCIENCE LETTERS, Vol: 479, Pages: 201-205, ISSN: 0304-3940
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- Citations: 21
Wall MB, Walker R, Smith AT, 2009, Functional imaging of the human superior colliculus: An optimised approach, NEUROIMAGE, Vol: 47, Pages: 1620-1627, ISSN: 1053-8119
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- Citations: 42
Lingnau A, Ashida H, Wall MB, et al., 2009, Speed encoding in human visual cortex revealed by fMRI adaptation, JOURNAL OF VISION, Vol: 9, ISSN: 1534-7362
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- Citations: 31
Wall MB, Lingnau A, Ashida H, et al., 2008, Selective visual responses to expansion and rotation in the human MT complex revealed by functional magnetic resonance imaging adaptation, EUROPEAN JOURNAL OF NEUROSCIENCE, Vol: 27, Pages: 2747-2757, ISSN: 0953-816X
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- Citations: 68
Wall MB, Smith AT, 2008, The representation of egomotion in the human brain, CURRENT BIOLOGY, Vol: 18, Pages: 191-194, ISSN: 0960-9822
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- Citations: 166
Smith AT, Wall MB, 2008, Sensitivity of human visual cortical areas to the stereoscopic depth of a moving stimulus, JOURNAL OF VISION, Vol: 8, ISSN: 1534-7362
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- Citations: 21
Begliomini C, Wall MB, Smith AT, et al., 2007, Differential cortical activity for precision and whole-hand visually guided grasping in humans, EUROPEAN JOURNAL OF NEUROSCIENCE, Vol: 25, Pages: 1245-1252, ISSN: 0953-816X
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- Citations: 91
Ashida H, Lingnau A, Wall MB, et al., 2007, fMRI adaptation reveals separate mechanisms for first-order and second-order motion, JOURNAL OF NEUROPHYSIOLOGY, Vol: 97, Pages: 1319-1325, ISSN: 0022-3077
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- Citations: 72
Smith A, Wall MB, 2007, Sensitivity to the stereoscopic depth of a moving surface in the human MT complex measured with fMRI adaptation, PERCEPTION, Vol: 36, Pages: 179-180, ISSN: 0301-0066
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- Citations: 1
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