Maladaptive emotional memories contribute to the persistence of numerous mental health disorders, including post-traumatic stress disorder (PTSD), drug addiction and obsessive-compulsive disorder (OCD). Using rodent behavioural models of the psychological processes relevant to these disorders, it is possible to identify potential treatment targets for the development of new therapies, including those based upon disrupting the reconsolidation of maladaptive emotional memories. Using examples from rodent models relevant to multiple mental health disorders, this talk will consider some of the opportunities and challenges that this approach provides.

Human neuroimaging research has consistently shown that drug addiction is associated with structural and functional changes within the orbitofrontal cortex (OFC). In view of the important role of the OFC in value-based decision-making, these changes have been hypothesised to bias choice towards drug use despite and at the expense of other competing pursuits, thereby explaining drug addiction. Here I will present in vivo recording data in the OFC supporting this hypothesis in a choice-based model of addiction where rats could choose between two actions, one rewarded by a drug (cocaine or heroin), the other by a nondrug alternative (saccharin).

This webinar is mainly focused on “Biomarkers for Addiction Treatment Development: fMRI Drug Cue Reactivity as an Example”. Biomarkers and Biotypes of Drug Addiction: funding opportunities at NIDA, Tanya Ramey (NIDA, US) Neuroimaging-based Biomarker Development for Clinical Trials, Owen Carmicheal (Pennington Biomedical Research Center, USA) ENIGMA-Addiction Cue Reactivity Initiative (ACRI) and Checklist, Hamed Ekhtiari (Laureate Institute for Brain Research, USA) ENIGMA-ACRI Checklist: Participant Characteristics, General fMRI Information, General Task Information, Cue Information, Task-related Assessments, Pre-Post Scanning Consideration (James Prisciandaro, Medical University of South Carolina, USA; Marc Kaufman, McLean Hospital/Harvard Medical School, USA; Anna Zilverstand, University of Minnesota; Torsten Wüstenberg, Charité Medical University Berlin, Germany; Falk Kiefer, University of Heidelberg, Germany; Amy Janes, Harvard Medical School, USA) How to Add fMRI Drug Cue Reactivity to the ENIGMA Consortium: Road Ahead, Hugh Garavan, University of Vermont)

Drug addiction is a chronically relapsing disorder characterized 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, I will present results of human neuroimaging studies, utilizing a multimodal approach (neuropsychology, functional magnetic resonance imaging, 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, our 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 I will also explore whether treatment (as usual) and 6-month abstinence enhance recovery in these brain-behavior compromises in treatment seeking cocaine addicted individuals. Promising neuroimaging 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 for empirically guiding the development of effective neurorehabilitation strategies (encompassing cognitive reappraisal and transcranial direct current stimulation) in drug addiction.