Chairs
Dr Amy L. Milton, University of Cambridge, UK
Dr Amy L. Milton, University of Cambridge, UK
Dr Amy L Milton is a University Lecturer in the Department of Psychology, University of Cambridge and the Ferreras-Willetts Fellow in Neuroscience at Downing College, Cambridge. She is a preclinical behavioural neuroscientist whose major research interest lies in understanding the neurochemical and molecular mechanisms underlying memory reconsolidation, which is the process by which memories can become unstable at retrieval and are subsequently restabilised in order to persist in the brain. She has a particular interest in the exploitation of basic memory mechanisms to develop treatments based upon memory disruption for a number of mental health disorders, including drug addiction, post-traumatic stress disorder and obsessive-compulsive disorder.
09:00-09:45
Neuroimaging in drug addiction: an eye towards intervention purposes
Professor Rita Goldstein, Icahn School of Medicine at Mount Sinai, USA
Abstract
Drug addiction is a chronically relapsing disorder characterised by compulsive drug use despite catastrophic personal consequences (e.g., loss of family, job) and even when the substance is no longer perceived as pleasurable. In this talk, Dr Goldstein will present results of human neuroimaging studies, utilising a multimodal approach (neuropsychology, functional magnetic resonance imaging, positron emission tomography, event-related potentials recordings), to explore the neurobiology underlying the core psychological impairments in drug addiction (impulsivity, drive/motivation, insight/awareness) as associated with its clinical symptomatology (intoxication, craving, bingeing, withdrawal). The focus of this talk is on understanding the role of the dopaminergic mesocorticolimbic circuit, and especially the prefrontal cortex, in higher-order executive dysfunction (e.g., disadvantageous decision-making such as trading a car for a couple of cocaine hits) in drug addicted individuals. The theoretical model that guides the presented research is called iRISA (Impaired Response Inhibition and Salience Attribution), postulating that abnormalities in the orbitofrontal cortex and anterior cingulate cortex, as related to dopaminergic dysfunction, contribute to the core clinical symptoms in drug addiction. Specifically, Dr Goldstein’s multi-modality program of research is guided by the underlying working hypothesis that drug addicted individuals disproportionately attribute reward value to their drug of choice at the expense of other potentially but no-longer-rewarding stimuli, with a concomitant decrease in the ability to inhibit maladaptive drug use. In this talk Dr Goldstein will also explore whether treatment (as usual) and 6-month abstinence enhance recovery in these brain-behaviour compromises in treatment seeking cocaine addicted individuals. Promising novel fMRI studies, which combine pharmacological (i.e., oral methylphenidate, or RitalinTM) and salient cognitive tasks or functional connectivity during resting-state, will be discussed as examples for using neuroimaging in the empirical guidance for the development of effective neurorehabilitation strategies in cocaine addiction.
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Professor Rita Goldstein, Icahn School of Medicine at Mount Sinai, USA
Professor Rita Goldstein, Icahn School of Medicine at Mount Sinai, USA
Dr Goldstein is a Professor of Psychiatry with a secondary appointment in the Department of Neuroscience at the Icahn School of Medicine at Mount Sinai (ISMMS) in NY. Dr Goldstein is chief of the Brain Imaging Center (BIC) at ISMMS; she also directs the NARC (Neuropsychoimaging of Addiction and Related Conditions) research group that uses multimodality functional neuroimaging methods to explore the neurobiological basis of impaired cognitive and emotional functioning in human drug addiction and other disorders of self-control. An important application of this research is to facilitate the development of intervention modalities that would improve treatment outcome in drug addiction and other chronically relapsing disorders of self-regulation. Nationally and internationally known for her neuroimaging and neuropsychological studies in drug addiction, Dr Goldstein formulated a theoretical model known as Impaired Response Inhibition and Salience Attribution (iRISA). The model uses multiple neuroimaging modalities—including MRI, EEG/ERP, PET—and neuropsychological tests to explore the neurobiological underpinnings of iRISA in drug addiction and related conditions. Dr Goldstein became fellow of the American College of Neuropsychopharmacology (ACNP) in January 2015, receiving the prestigious Joel Elkes Research Award in 2012 and the Jacob P. Waletzky Award in 2013.
09:45-10:30
Addictive behaviour in experimental animals: prospects for translation
Professor Barry Everitt FMedSci FRS, University of Cambridge, UK
Abstract
Drug addiction is characterised by loss of control over drug seeking behaviour such that it becomes less goal-directed and more habitual, elicited by drug associated conditioned stimuli (CSs) and ultimately compulsive; it is difficult to relinquish drug seeking habits and there is a high propensity to relapse in abstinence. These complex behavioural processes have been successfully modelled in animals, especially rats, by exploiting the fact that they will self-adminster drugs that are addictive in humans. The group has developed behavioural procedures that have allowed them to model the interactions between pavlovian and instrumental learning and memory processes that underlie addictive behaviour. This has enabled the group to define the circuitry mediating that the transition from goal-directed to habitual drug seeking, as well as the neural basis of the impact of drug CSs on drug seeking and relapse, and also the mechanisms resulting in compulisve drug seeking, such as loss of prefrontal inhibitory control. These animal experimental data increasingly align with data from imaging studies in humans, especially the impact of drug CSs that elicit craving and relapse. Pharmacological and/or psychological treatments that diminish the impact of drug CSs on drug seeking and relapse and or decrease the compulsive behaviour would clearly have clinical utility. Pharmacological agents from several drug classes, including a µ-opioid receptor antagonist, can prevent cocaine, heroin and alcohol seeking and thereby promote abstinence. Serotonin re-uptake inhibitors or a selective µ-opioid receptor antagonist can decrease compulsive cocaine or alcohol seeking, respectively. Increasing top-down inhibtory control can also reduce compulsive drug seeking in both rats and humans. More recently, the group has shown that retrieving drug memories by presenting drug CSs results in their destabilisation in the brain and that undergo restablilisation, or ‘reconsolidation’, in order to persist. Preventing drug memory reconsolidation, for example by anatagonising NMDA or ß-adrenoceptors given at memory retrieval, can result in the long-term reduction or elimination of the ability of drug CSs to elicit drug seeking and relapse. The potential, as well as challenges, of translation to the clinic of these putative treatment approaches will be discussed.
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Professor Barry Everitt FMedSci FRS, University of Cambridge, UK
Professor Barry Everitt FMedSci FRS, University of Cambridge, UK
Barry Everitt is Professor of Behavioural Neuroscience in the Department of Psychology at the University of Cambridge. His is President of the Federation of European Neuroscience Societies and is an elected Fellow of the Royal Society. Among many service roles, he has been President of the British Association for Psychopharmacology, the European Brain and Behaviour Society and the European Behavioural Pharmacology Society. He was a Scientific Counsellor for the National Institute on Drug Abuse (NIDA, Baltimore, 2002-6) and is a member of the Council of the Society for Neuroscience. He was Editor-in-Chief of the European Journal of Neuroscience from1997-2008 and is a Reviewing Editor for the journal Science. He has received several awards including the APA Distinguished Scientific Contribution Award (2011) and the Fondation Ipsen Neuronal Plasticity Prize (2014). His research is concerned with understanding the neural and psychological mechanisms underlying the vulnerability to, and development of, compulsive drug use in addiction, as well as the development of pharmacological and psychological treatments that prevent relapse.
10:30-11:15
Neurobiology of compulsive eating
Dr Pietro Cottone, Boston University, USA
Abstract
Compulsive eating behaviour is a transdiagnostic construct that is characteristic of medical and psychiatric conditions such as forms of obesity and eating disorders. It has been hypothesised that one of the mechanisms underlying compulsive eating involves highly palatable food acquiring negative reinforcing properties; that is, the need to alleviate a negative emotional state induced by withdrawal from high palatable food drives overeating. The group observed that rats undergoing chronic, intermittent access to highly palatable food showed hypophagia and decreased motivation for a less palatable food alternative. Withdrawal from palatable food was associated with spontaneous emotional signs of palatable food-withdrawal, including anxiety- and depressive-like behaviour. In addition, cycling rats showed a weakened ability for contextual spatial processing during withdrawal. According to a negatively reinforced mechanism, renewing access to highly palatable food normalised all withdrawal-dependent maladaptive behavioural outcomes, and induced overeating. Palatable-food withdrawal was also found to be accompanied by increased corticotropin-releasing factor (CRF) expression in the central nucleus of the amygdala and administration of a selective CRF1 receptor antagonist directly into this brain area was able to block both the overeating of palatable food and the negative emotional state. Interestingly, diet cycled rats also showed reduced expression of immature neurons in the dentate gyrus of the hippocampus, as well as a withdrawal-dependent decrease of proliferating cells. These results suggest that withdrawal from palatable food, analogous to abstinence from abused drugs, causes profound behavioural and molecular neuroadaptations which promote and sustain compulsive eating.
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Dr Pietro Cottone, Boston University, USA
Dr Pietro Cottone, Boston University, USA
Dr Pietro Cottone is an Associate Professor in the Departments of Pharmacology and Psychiatry and co-director of the Laboratory of Addictive Disorders at Boston University School of Medicine. A major focus area of Dr Cottone’s research is the study of the neurobiological mechanisms of compulsive eating. He received his Ph.D. in Pharmacology in 2007 from the University of Rome “La Sapienza”. He was a postdoctoral fellow at The Scripps Research Institute with Drs Eric Zorrilla and George Koob. He was awarded one of the first Pathway for Independence career development awards (K99/R00) from NIDA/NIH. In 2009, he was appointed as an Assistant Professor in the Departments of Pharmacology and Psychiatry at Boston University School of Medicine. In 2010, he was awarded one of the prestigious Biobehavioral Research Awards for Innovative New Scientists (BRAINS) grants which was established by the NIMH/NIH to support innovative research of outstanding early-stage scientists. In 2013, he was promoted to Associate Professor. In 2014, he became Associate Member of the American College of Neuropsychopharmacology. In his spare time, Dr Cottone composes progressive/psychedelic rock music and plays chess.
11:45-12:30
Deep Brain Stimulation in obsessive compulsive disorder: a decade of experience
Professor Damiaan Denys, University of Amsterdam, The Netherlands
Abstract
OCD is considered one of the most disabling psychiatric disorders, causing serious impairment in patients’ daily functioning and affecting professional, social, and personal lives. Thanks to a wide range of available pharmacologic treatments and cognitive behavioural therapy (CBT), most patients can be treated to a satisfactory level. However, 10% of patients experience inadequate response and remain severely ill. In the last decades, neuromodulating techniques have emerged as promising alternatives for the treatment of OCD. Different from the rather aspecific pharmacologic modulation of drug therapy, neuromodulation techniques enable modulation of distinct neuronal circuits by targeting specific brain structures. OCD may be particularly suitable for these interventions because of its strong link to discrete neuro-anatomic networks. Neuroimaging studies have consistently related OCD to aberrant activity within the orbitofronto-striato-thalamo-cortical (CSTC) network. A major advantage of neuromodulation is its potential of adjustable and reversible brain network manipulation. This lecture reviews studies on DBS for OCD.
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Professor Damiaan Denys, University of Amsterdam, The Netherlands
Professor Damiaan Denys, University of Amsterdam, The Netherlands
Damiaan Denys is Professor at the University of Amsterdam (UVA), Chair of the Department of Psychiatry at the Academic Medical Center in Amsterdam (AMC), and member of The Netherlands Institute for Neuroscience (NIN).
Denys conducts clinical and neurobiological research into anxiety, impulsive-compulsive disorders, and neuromodulation. His scientific research is characterised by a translational approach and makes use of clinical trials, animal models, neuroimaging, and neurogenetics. A particular focus of his research is the development of deep brain stimulation (DBS) for psychiatric disorders.
Denys studied Philosophy and Medicine at the KU Leuven (Belgium) and obtained his doctorate cum laude from Utrecht University (Netherlands) with a dissertation entitled On certainty: studies in obsessive compulsive disorder.
12:30-13:15
Dissecting OCD mechanisms using advanced technologies in mice
Dr Susanne Ahmari, University of Pittsburgh, USA
Abstract
Ahmari and colleagues explore the neural mechanisms underlying perseverative thoughts and actions. This topic is of general importance because compulsive behaviours are a central component of Obsessive Compulsive Disorder (OCD), as well as prominent, disabling, and notoriously-treatment resistant symptoms of many severe psychiatric disorders, including autism, schizophrenia, and addiction. Although OCD symptoms have been broadly linked to abnormal activity in cortical-basal ganglia circuits via human imaging studies, there is still a quite limited understanding of how maladaptive repetitive behaviours are encoded in the brain. The Ahmari lab is therefore using novel technologic approaches and statistical strategies to determine: 1) which neural circuits underlie maladaptive repetitive behaviours, 2) how these behaviours are encoded in the brain, and 3) when the neural code changes as these behaviours develop and resolve.
In previous work the Ahmari lab demonstrated that repeated pulses of brief but abnormal activity delivered by optogenetic stimulation of projections from orbitofrontal cortex (OFC) to ventromedial striatum (VMS) leads to long-lasting perseverative grooming, a mouse behaviour linked to OCD. This compulsive grooming behaviour was associated with increased neural activity in the striatum. Dr Ahmari will discuss how her lab is now using advanced in vivo approaches including optogenetics, electrophysiology, and head-mounted microscopy to identify the specific activity patterns, cell-types, and circuits responsible for this pathologic plasticity in the brain. She will also describe approaches to ground basic neuroscience experiments in findings from clinical studies.
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Dr Susanne Ahmari, University of Pittsburgh, USA
Dr Susanne Ahmari, University of Pittsburgh, USA
Susanne Ahmari, MD, PhD, is an Assistant Professor of Psychiatry at University of Pittsburgh, and Director of the Translational OCD Laboratory. Dr Ahmari received her MD-PhD from Stanford, where she used advanced microscopy techniques to make the first real-time observations of CNS synapse formation. She then performed psychiatry residency at Columbia University, where she developed clinical expertise in treatment of OCD and anxiety disorders. Dr Ahmari received an NIMH K08 Career Development Award in 2010 to develop translational research approaches in OCD. During her K08, she pioneered the use of optogenetics to dissect neural circuits underlying OCD-relevant behaviours (Ahmari et al, Science, 2013).
Dr Ahmari’s research programme at University of Pittsburgh integrates basic neuroscience approaches and cutting-edge technology with clinical studies of OCD patients. Her work is currently supported by an NIMH BRAINS Award, MQ Fellows Award, Burroughs Wellcome Career Award, NARSAD Young Investigator Award, and McKnight Scholar Award.